2，3，7，8-四氯二苯并二噁英所致先天性肾积水的发生机制及其预防的实验研究
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摘要
目的:研究2,3,7,8-四氯二苯并二噁英(2,3,7,8- tetrachlorodibenzodioxin, TCDD)所致先天性肾积水的发生机制,以及槲皮素对先天性肾积水的预防作用。
方法:1.利用TCDD诱导建立小鼠先天性肾积水动物模型。在C57BL/6J孕鼠第12个妊娠日(gestational day, GD),实验组以TCDD(25μg/kg)灌胃,对照组以玉米油灌胃。GD18,统计胎鼠数及存活率;解剖胎鼠,观察畸形发生情况。对孕鼠及胎鼠的各主要脏器进行组织学检查,并对胎鼠的肾脏及输尿管进行超微结构观察。
2.采用比较蛋白质组学方法探讨TCDD致小鼠先天性肾积水的分子机制。GD12,TCDD组C57BL/6J孕鼠以TCDD(25μg/kg)灌胃,对照组孕鼠以玉米油灌胃。GD18,取胎鼠上尿路,提取组织总蛋白,进行双向凝胶电泳,图像分析两组间差异表达的蛋白质点,将差异明显的蛋白质点进行质谱分析后于数据库中检索鉴定,并应用免疫组化方法对鉴定出的蛋白质进行验证。体外培养GD12的胎鼠泌尿系统, Prx 1组加peroxiredoxin 1(Prx 1)蛋白(终浓度为1:100),对照组加等量培养基,培养6天后,进行组织学检查,了解输尿管粘膜上皮增殖情况及输尿管管腔有无狭窄。
3.观察槲皮素对小鼠先天性肾积水的预防作用。GD12,C57BL/6J孕鼠随机分为四组:对照组以玉米油灌胃,TCDD组以TCDD(25μg/kg)灌胃,槲皮素组以槲皮素(100 mg/kg)灌胃,TCDD+槲皮素组以槲皮素(100 mg/kg)及TCDD(25μg/kg)灌胃。GD18,统计胎鼠数及存活率,检查畸形发生情况,并留取胎鼠泌尿系统作组织学观察及免疫组化检测。
结果:1.实验组胎鼠双侧肾积水及上段输尿管积水发生率为100%(3级肾积水为86.2%,4级肾积水为13.8%)。实验组胎鼠肾间质纤维化,中下段输尿管粘膜移行上皮增生,管腔变窄,肾小管上皮细胞肿胀,结构模糊,可见膜性结构破裂,输尿管上皮细胞核大,核仁明显,靠边,染色质丰富,常染色质发达,异染色质少。对照组胎鼠肾脏及输尿管未见异常。实验组胎鼠肾积水发生率高于对照组(P<0.01)。
2.经双向电泳、质谱分析及数据库查询后,最终在肾积水胎鼠上尿路中鉴定出12种表达增强的蛋白质,分别是:Prx 1蛋白、钙粘蛋白6、γ-肌动蛋白、根蛋白、结蛋白、II型转化生长因子β受体、嗜铬颗粒蛋白B、血清白蛋白前体、转铁蛋白、假说蛋白LOC70984、Lipk蛋白和锌指蛋白336。免疫组化结果显示,Prx 1蛋白在肾积水胎鼠输尿管粘膜上皮表达增强。经体外培养6天后,与对照组相比,Prx 1组输尿管粘膜上皮增生明显,上皮层增厚,输尿管管腔狭窄(P<0.01)。
3.槲皮素对小鼠先天性肾积水的预防作用。各组孕鼠每日体重增长无显著差异(P>0.05),一般情况正常,无流产及早产,产仔数无显著差异(P>0.05);各组胎鼠体重无显著差异(P>0.05),均为活胎,无死胎及吸收胎。对照组及槲皮素组胎鼠无肾盂及上段输尿管积水发生。TCDD组胎鼠双侧肾盂及上段输尿管积水发生率为100%(3级肾积水84.1%,4级肾积水15.9%),TCDD+槲皮素组为13.4%(均为3级肾积水),差异具有显著性(P<0.05)。免疫组织化学检测结果:对照组与槲皮素组胎鼠输尿管粘膜上皮Prx 1蛋白均呈阴性表达;在TCDD组及TCDD+槲皮素组具有肾积水的胎鼠输尿管粘膜上皮呈阳性表达。TCDD组胎鼠输尿管粘膜上皮Prx 1蛋白阳性表达率(100%)高于TCDD+槲皮素组(13.4%),差异具有显著性(P<0.05)。
结论:1.TCDD诱导出的C57BL/6J胎鼠双侧肾积水动物模型在病理学表现上与人类肾盂输尿管连接处梗阻(ureteropelvic junction obstruction, UPJO)相似,适用于UPJO的病因学及发病机制等方面的研究。
2.TCDD致胎鼠肾积水的分子机制与Prx 1蛋白密切相关:TCDD通过诱导胎鼠氧化应激,使Prx 1蛋白反应性升高以对抗氧化应激,同时刺激输尿管粘膜上皮增生,致使其管腔变窄,产生不全性梗阻导致肾积水。
3.槲皮素能有效降低TCDD所致胎鼠肾积水的发生率,其对小鼠先天性肾积水的预防作用与抑制胎鼠输尿管粘膜上皮Prx 1蛋白表达有关。
Objective: To research pathogenesis of congenital hydronephrosis induced by 2,3,7,8-tetrachlorodibenzodioxin(TCDD) and the effect of quercetin prevent with the disease.
Methods: 1. Animal model of congenital hydronephrosis was constructed with TCDD in mice.Pregnant C57BL/6J mice in treatment group were given TCDD(25μg/kg) with intragastric administration,corn oil was given to pregnant mice with same method in control group on gestational day(GD) 12. Number and survival rate of fetus were calculated,teratogeny of fetus was distinguished,main organs of dams and fetus were gain for histology examination,and ultramicrostructure of fetal kidney and ureter was observed with transmission electron microscope(TEM),on GD18.
2. Compare proteomics study on molecular mechanisms of congenital hydronephrosis induced by TCDD in mice. Pregnant C57BL/6J mice in TCDD group were given TCDD(25μg/kg) with intragastric administration,corn oil was given to pregnant mice with same method in control group on GD12. Fetal upper urinary tract tissues were gain for abstracting total protein on GD18. Following,the total protein was separated by two dimensional gel electrophoresis. The differentially expressed proteins between the two groups were compared using image analysis software.The proteins with significant difference were identified by mass spectrometry. The expression of the differential protein was confirmed by immunohistochemistry. Fetal urinary system was gain to culture in vitro, on GD12. Peroxiredoxin 1(Prx 1) protein(final concentration was 1:100) was added in Prx 1 group,same volume nutritive medium was added in control group.After 6 day culture, histology examine was carried out to assess epitheliosis of mucous membrane of ureter and lumina of ureter.
3. The effect of quercetin prevent with congenital hydronephrosis induced by TCDD in mice. Pregnant C57BL/6J mice was divided into four groups randomly on GD12.Corn oil was given pregnant mice with intragastric administration in control group,TCDD(25μg/kg) was given in TCDD group,quercetin(100 mg/kg) was given in qercetin group, TCDD(25μg/kg) and quercetin(100 mg/kg) was given in TCDD+qercetin group. Number and survival rate of fetus were calculated,teratogeny of fetus was distinguished, fetal urinary system was gain for histology examine and immunohistochemistry analysis,on GD18.
Results: 1.On GD18,incidence rate of bilateral hydronephrosis and hydroureter at superior segment in fetus were 100%(grade 3 hydronephrosis was 86.2%,grade 4 hydronephrosis was 13.8%) in treatment group. Renal interstitial fibrosis, epithelial proliferation in mucous membrane of middle and inferior ureter, narrow ureter lumina was found in fetus with hydronephrosis. Epithelial cells of nephric tubule was swelling with vague and break structure, epithelial cells of ureter was shown with big nucleus, gross nucleoli,rich caryotin,prosperous euchromatin and few heterochromatin,which were found by TEM in treatment group. Fetal kidneys and ureters were normal in control group on GD18. Hydronephrosis incidence of fetal in treatment group was greater than control group(P<0.01).
2. Twelve proteins expression was up-regulated in upper urinary tract of mice fetus with hydronephrosis including Prx 1, cadherin 6, gamma-actin, radixin, desmin, type II transforming growth factor-beta receptor, chromogranin B, serum albumin precursor, transferring, hypothetical protein LOC70984, Lipk protein and zinc finger protein 336. Immunohistochemistry analysis display that Prx 1 protein expression was up-regulated in epithelium mucosae of ureter in mice fetus with hydronephrosis. Epitheliosis of mucous membrane of ureter was outstanding, epithelial lamina was thicken and lumina of ureter was narrow after treating with Prx 1 protein compare with control group(P<0.01).
3. Body weight everyday wasn’t significant deviation (P>0.05), abortion and immature labor wasn’t found, general state of health was normal for pregnance mice in all groups.Number and body weight of fetus wasn’t significant deviation(P>0.05),all feus were live,no absorption in all groups.All fetus were normal and no malformation was found in control group and quercetin group on GD18. Incidence rate of bilateral hydronephrosis and hydroureter was 100%(grade 3 hydronephrosis was 84.1%,grade 4 hydronephrosis was 15.9%) in TCDD group fetus on GD18. Incidence rate of bilateral hydronephrosis and hydroureterwas 13.4%(all were grade 3) in TCDD+quercetin group fetus on GD18. The difference of incidence rate between TCDD group and TCDD+quercetin group was significant(P<0.05). Prx 1 protein expression in epithelium of mucous membrane of fetal ureter was negative in control group and quercetin group,was positive in TCDD group,was positive in TCDD+quercetin group fetus with hydronephrosis on GD18. The positive rate for Prx 1 protein expression in epithelium of mucous membrane of fetal ureter was 100% in TCDDgroup,which is greater than TCDD+quercetin group (13.4%)(P<0.05).
Conclusion: 1. Pathology of the animal model with congenital hydronephrosis in C57BL/6J fetal mice is similar to ureteropelvic junction obstruction(UPJO) of human being. The animal model is suitable to study on aetiology and pathogenesy of UPJO.
2. Molecular mechanisms of congenital hydronephrosis induced by TCDD in fetal mice is related with Prx 1 protein: oxidative stress is generated by TCDD, following up-regulated Prx 1 protein,which made epithelium mucosae of ureter proliferate and ureteral lumen be narrow.
3. Incidence rate congenital hydronephrosis induced by TCDD in C57BL/6J fetal mice may be cut down effectually by quercetin. Effect of quercetin prevent with congenital hydronephrosis is related with that Prx 1 protein expression is inhibited in epithelium of mucous membrane of fetal ureter.
方法:1.利用TCDD诱导建立小鼠先天性肾积水动物模型。在C57BL/6J孕鼠第12个妊娠日(gestational day, GD),实验组以TCDD(25μg/kg)灌胃,对照组以玉米油灌胃。GD18,统计胎鼠数及存活率;解剖胎鼠,观察畸形发生情况。对孕鼠及胎鼠的各主要脏器进行组织学检查,并对胎鼠的肾脏及输尿管进行超微结构观察。
2.采用比较蛋白质组学方法探讨TCDD致小鼠先天性肾积水的分子机制。GD12,TCDD组C57BL/6J孕鼠以TCDD(25μg/kg)灌胃,对照组孕鼠以玉米油灌胃。GD18,取胎鼠上尿路,提取组织总蛋白,进行双向凝胶电泳,图像分析两组间差异表达的蛋白质点,将差异明显的蛋白质点进行质谱分析后于数据库中检索鉴定,并应用免疫组化方法对鉴定出的蛋白质进行验证。体外培养GD12的胎鼠泌尿系统, Prx 1组加peroxiredoxin 1(Prx 1)蛋白(终浓度为1:100),对照组加等量培养基,培养6天后,进行组织学检查,了解输尿管粘膜上皮增殖情况及输尿管管腔有无狭窄。
3.观察槲皮素对小鼠先天性肾积水的预防作用。GD12,C57BL/6J孕鼠随机分为四组:对照组以玉米油灌胃,TCDD组以TCDD(25μg/kg)灌胃,槲皮素组以槲皮素(100 mg/kg)灌胃,TCDD+槲皮素组以槲皮素(100 mg/kg)及TCDD(25μg/kg)灌胃。GD18,统计胎鼠数及存活率,检查畸形发生情况,并留取胎鼠泌尿系统作组织学观察及免疫组化检测。
结果:1.实验组胎鼠双侧肾积水及上段输尿管积水发生率为100%(3级肾积水为86.2%,4级肾积水为13.8%)。实验组胎鼠肾间质纤维化,中下段输尿管粘膜移行上皮增生,管腔变窄,肾小管上皮细胞肿胀,结构模糊,可见膜性结构破裂,输尿管上皮细胞核大,核仁明显,靠边,染色质丰富,常染色质发达,异染色质少。对照组胎鼠肾脏及输尿管未见异常。实验组胎鼠肾积水发生率高于对照组(P<0.01)。
2.经双向电泳、质谱分析及数据库查询后,最终在肾积水胎鼠上尿路中鉴定出12种表达增强的蛋白质,分别是:Prx 1蛋白、钙粘蛋白6、γ-肌动蛋白、根蛋白、结蛋白、II型转化生长因子β受体、嗜铬颗粒蛋白B、血清白蛋白前体、转铁蛋白、假说蛋白LOC70984、Lipk蛋白和锌指蛋白336。免疫组化结果显示,Prx 1蛋白在肾积水胎鼠输尿管粘膜上皮表达增强。经体外培养6天后,与对照组相比,Prx 1组输尿管粘膜上皮增生明显,上皮层增厚,输尿管管腔狭窄(P<0.01)。
3.槲皮素对小鼠先天性肾积水的预防作用。各组孕鼠每日体重增长无显著差异(P>0.05),一般情况正常,无流产及早产,产仔数无显著差异(P>0.05);各组胎鼠体重无显著差异(P>0.05),均为活胎,无死胎及吸收胎。对照组及槲皮素组胎鼠无肾盂及上段输尿管积水发生。TCDD组胎鼠双侧肾盂及上段输尿管积水发生率为100%(3级肾积水84.1%,4级肾积水15.9%),TCDD+槲皮素组为13.4%(均为3级肾积水),差异具有显著性(P<0.05)。免疫组织化学检测结果:对照组与槲皮素组胎鼠输尿管粘膜上皮Prx 1蛋白均呈阴性表达;在TCDD组及TCDD+槲皮素组具有肾积水的胎鼠输尿管粘膜上皮呈阳性表达。TCDD组胎鼠输尿管粘膜上皮Prx 1蛋白阳性表达率(100%)高于TCDD+槲皮素组(13.4%),差异具有显著性(P<0.05)。
结论:1.TCDD诱导出的C57BL/6J胎鼠双侧肾积水动物模型在病理学表现上与人类肾盂输尿管连接处梗阻(ureteropelvic junction obstruction, UPJO)相似,适用于UPJO的病因学及发病机制等方面的研究。
2.TCDD致胎鼠肾积水的分子机制与Prx 1蛋白密切相关:TCDD通过诱导胎鼠氧化应激,使Prx 1蛋白反应性升高以对抗氧化应激,同时刺激输尿管粘膜上皮增生,致使其管腔变窄,产生不全性梗阻导致肾积水。
3.槲皮素能有效降低TCDD所致胎鼠肾积水的发生率,其对小鼠先天性肾积水的预防作用与抑制胎鼠输尿管粘膜上皮Prx 1蛋白表达有关。
Objective: To research pathogenesis of congenital hydronephrosis induced by 2,3,7,8-tetrachlorodibenzodioxin(TCDD) and the effect of quercetin prevent with the disease.
Methods: 1. Animal model of congenital hydronephrosis was constructed with TCDD in mice.Pregnant C57BL/6J mice in treatment group were given TCDD(25μg/kg) with intragastric administration,corn oil was given to pregnant mice with same method in control group on gestational day(GD) 12. Number and survival rate of fetus were calculated,teratogeny of fetus was distinguished,main organs of dams and fetus were gain for histology examination,and ultramicrostructure of fetal kidney and ureter was observed with transmission electron microscope(TEM),on GD18.
2. Compare proteomics study on molecular mechanisms of congenital hydronephrosis induced by TCDD in mice. Pregnant C57BL/6J mice in TCDD group were given TCDD(25μg/kg) with intragastric administration,corn oil was given to pregnant mice with same method in control group on GD12. Fetal upper urinary tract tissues were gain for abstracting total protein on GD18. Following,the total protein was separated by two dimensional gel electrophoresis. The differentially expressed proteins between the two groups were compared using image analysis software.The proteins with significant difference were identified by mass spectrometry. The expression of the differential protein was confirmed by immunohistochemistry. Fetal urinary system was gain to culture in vitro, on GD12. Peroxiredoxin 1(Prx 1) protein(final concentration was 1:100) was added in Prx 1 group,same volume nutritive medium was added in control group.After 6 day culture, histology examine was carried out to assess epitheliosis of mucous membrane of ureter and lumina of ureter.
3. The effect of quercetin prevent with congenital hydronephrosis induced by TCDD in mice. Pregnant C57BL/6J mice was divided into four groups randomly on GD12.Corn oil was given pregnant mice with intragastric administration in control group,TCDD(25μg/kg) was given in TCDD group,quercetin(100 mg/kg) was given in qercetin group, TCDD(25μg/kg) and quercetin(100 mg/kg) was given in TCDD+qercetin group. Number and survival rate of fetus were calculated,teratogeny of fetus was distinguished, fetal urinary system was gain for histology examine and immunohistochemistry analysis,on GD18.
Results: 1.On GD18,incidence rate of bilateral hydronephrosis and hydroureter at superior segment in fetus were 100%(grade 3 hydronephrosis was 86.2%,grade 4 hydronephrosis was 13.8%) in treatment group. Renal interstitial fibrosis, epithelial proliferation in mucous membrane of middle and inferior ureter, narrow ureter lumina was found in fetus with hydronephrosis. Epithelial cells of nephric tubule was swelling with vague and break structure, epithelial cells of ureter was shown with big nucleus, gross nucleoli,rich caryotin,prosperous euchromatin and few heterochromatin,which were found by TEM in treatment group. Fetal kidneys and ureters were normal in control group on GD18. Hydronephrosis incidence of fetal in treatment group was greater than control group(P<0.01).
2. Twelve proteins expression was up-regulated in upper urinary tract of mice fetus with hydronephrosis including Prx 1, cadherin 6, gamma-actin, radixin, desmin, type II transforming growth factor-beta receptor, chromogranin B, serum albumin precursor, transferring, hypothetical protein LOC70984, Lipk protein and zinc finger protein 336. Immunohistochemistry analysis display that Prx 1 protein expression was up-regulated in epithelium mucosae of ureter in mice fetus with hydronephrosis. Epitheliosis of mucous membrane of ureter was outstanding, epithelial lamina was thicken and lumina of ureter was narrow after treating with Prx 1 protein compare with control group(P<0.01).
3. Body weight everyday wasn’t significant deviation (P>0.05), abortion and immature labor wasn’t found, general state of health was normal for pregnance mice in all groups.Number and body weight of fetus wasn’t significant deviation(P>0.05),all feus were live,no absorption in all groups.All fetus were normal and no malformation was found in control group and quercetin group on GD18. Incidence rate of bilateral hydronephrosis and hydroureter was 100%(grade 3 hydronephrosis was 84.1%,grade 4 hydronephrosis was 15.9%) in TCDD group fetus on GD18. Incidence rate of bilateral hydronephrosis and hydroureterwas 13.4%(all were grade 3) in TCDD+quercetin group fetus on GD18. The difference of incidence rate between TCDD group and TCDD+quercetin group was significant(P<0.05). Prx 1 protein expression in epithelium of mucous membrane of fetal ureter was negative in control group and quercetin group,was positive in TCDD group,was positive in TCDD+quercetin group fetus with hydronephrosis on GD18. The positive rate for Prx 1 protein expression in epithelium of mucous membrane of fetal ureter was 100% in TCDDgroup,which is greater than TCDD+quercetin group (13.4%)(P<0.05).
Conclusion: 1. Pathology of the animal model with congenital hydronephrosis in C57BL/6J fetal mice is similar to ureteropelvic junction obstruction(UPJO) of human being. The animal model is suitable to study on aetiology and pathogenesy of UPJO.
2. Molecular mechanisms of congenital hydronephrosis induced by TCDD in fetal mice is related with Prx 1 protein: oxidative stress is generated by TCDD, following up-regulated Prx 1 protein,which made epithelium mucosae of ureter proliferate and ureteral lumen be narrow.
3. Incidence rate congenital hydronephrosis induced by TCDD in C57BL/6J fetal mice may be cut down effectually by quercetin. Effect of quercetin prevent with congenital hydronephrosis is related with that Prx 1 protein expression is inhibited in epithelium of mucous membrane of fetal ureter.
引文
[1] Csaicsich D, Greenbaum LA, Aufricht C. Upper urinary tract: when is obstruction obstruction[J]? Curr Opin Urol. 2004, 14(4):213-217.
[2] Belarmino JM, Kogan BA. Management of neonatal hydronephrosis[J]. Early Hum Dev.2006, 82(1):9-14.
[3] Woodward M, Frank D.Postnatal management of antenatal hydronephrosis[J]. BJU Int.2002, 89(2):149–156.
[4] Nishimura N, Matsumura F, Vogel CF, et al. Critical role of cyclooxygenase-2 activation in pathogenesis of hydronephrosis caused by lactational exposure of mice to dioxin[J]. Toxicol Appl Pharmacol. 2008, 231(3):374-383.
[5] Nishimura N, Yonemoto J, Nishimura H, et al. Localization of cytochrome P450 1A1 in a specific region of hydronephrotic kidney of rat neonates lactationally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Toxicology. 2006, 227(1-2): 117-126.
[6] Kransler KM, McGarrigle BP, Olson JR. Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig[J]. Toxicology. 2007, 229(3):214-225.
[7] Hung YC, Huang GS, Sava VM, et al. Protective effects of tea melanin against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity: antioxidant activity and aryl hydrocarbon receptor suppressive effect[J]. Biol Pharm Bull. 2006, 29(11): 2284-2291.
[8] Mimura J, Fujii-Kuriyama Y. Functional role of AhR in the expression of toxic effects by TCDD[J]. Biochim Biophys Acta. 2003, 1619(3):263-268.
[9] Ciolino HP, Daschner PJ, Yeh GC. Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially[J]. Biochem J. 1999, 340( Pt 3):715-722.
[10] Vásquez-Garzón VR, Arellanes-Robledo J, García-Román R, et al. Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism[J]. Free Radic Res. 2009, 43(2):128-137.
[1] Kransler KM, McGarrigle BP, Olson JR.Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig[J]. Toxicology. 2007, 229(3):214-225.
[2] Jang JY, Park D, Shin S, et al. Antiteratogenic effect of resveratrol in mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin.Eur J Pharmacol[J]. 2008, 591(1-3):280-283.
[3] Ishida T, Oshimo T, Nishimura A, et al. Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone[J]. Biol Pharm Bull. 2004, 27(9):1397-1402.
[4] Jang JY,Shin S,Choi BI,et al.Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero[J].Reprod Toxicol.2007, 24(3-4):303-309.
[5] Guerin F, Azoulay R, Berrebi D, et al.Partial unilateral ureteral obstruction in newborn mice: magnetic resonance imaging and pathology studies[J].J Urol. 2008, 179(4):1553-1563.
[6] Horton CE Jr,Davisson MT,Jacobs JB,et al.Congenital progressive hydrone-phrosis in mice: a new recessive mutation[J]. J Urol. 1988, 140(5 Pt 2): 1310-1315.
[7] McDill BW, Li SZ, Kovach PA, et al. Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation[J]. Proc Natl Acad Sci U S A. 2006, 103(18):6952-6957.
[8] Friedman J, Hoyer JR, McCormick B, et al. Congenital unilateral hydronephrosis in the rat[J]. Kidney Int. 1979, 15(5):567-571.
[9] Tauchi K, Kanehara H. Hypertension and the renin-angiotensin system in the congenital hydronephrosis rat with non-obstructive pelviureteric junction abnormalities[J]. Exp Nephrol. 1996, 4(1):60-64.
[10] Dawrant MJ, Giles S, Bannigan J, et al. Adriamycin produces a reproducible teratogenic model of vertebral, anal, cardiovascular, tracheal, esophageal, renal, and limb anomalies in the mouse[J]. J Pediatr Surg. 2007, 42(10):1652-1658.
[11] Haruyama N, Cho A, Kulkarni AB.Overview: engineering transgenic constructs and mice[J]. Curr Protoc Cell Biol. 2009 Mar;Chapter 19:Unit 19.10.
[12] Bryant PL,Reid LM,Schmid JE, et al. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on fetal mouse urinary tract epithelium in vitro[J]. Toxicology. 2001, 162(1):23-34.
[13] Bryant PL,Schmid JE,Fenton SE,et al.Teratogenicity of 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) in mice lacking the expression of EGF and/or TGF-alpha[J].Toxicol Sci.2001, 62(1):103-114.
[14]谢小志,蔡正林,张海燕,等.先天性肾盂输尿管连接处狭窄的临床病理分析[J].临床与实验病理学杂志. 2004, 20(3):379-380.
[1] Kawakami T, Ito T, Ohsako S,et al. Possible involvement of arylhydrocarbon receptor variants in TCDD-induced thymic atrophy and XRE-dependent transcriptional activity in Wistar Hannover GALAS rats[J]. J Toxicol Sci. 2009,34(2): 209-220.
[2] Mandal PK. Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology[J]. J Comp Physiol [B]. 2005,175(4):221-230.
[3] Westerink WM, Stevenson JC, Schoonen WG. Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition[J]. Arch Toxicol. 2008,82(12):909-921.
[4] Service RF. Proteomics. Can Celera do it again[J]? Science. 2000,287(5461): 2136-2138.
[5] Wasinger VC, Cordwell SJ, Cerpa-Poljak A, et al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis. 1995,16(7): 1090-1094.
[6] Kim SU, Hwang CN, Sun HN, et al. Peroxiredoxin I is an indicator of microglia activation and protects against hydrogen peroxide-mediated microglial death[J]. Biol Pharm Bull.2008, 31(5):820-825.
[7] Immenschuh S, Baumgart-Vogt E. Peroxiredoxins,oxidative stress, and cell proliferation[J]. Antioxid Redox Signal. 2005, 7(5-6):768-777.
[8] Lee YM, Park SH, Shin DI, et al. Oxidative modification of peroxiredoxin is associated with drug-induced apoptotic signaling in experimental models of Parkinson disease[J]. J Biol Chem. 2008, 283(15):9986-9998.
[9] Mu ZM, Yin XY, Prochownik EV. Pag, a putative tumor suppressor, interacts with the Myc Box II domain of c-Myc and selectively alters its biological function and target gene expression[J]. J Biol Chem. 2002, 277(45):43175-43184.
[10] Daly KA, Lefévre C, Nicholas K, et al. Characterization and expression of Peroxiredoxin 1 in the neonatal tammar wallaby (Macropus eugenii) [J]. Comp Biochem Physiol B Biochem Mol Biol. 2008, 149(1):108-119.
[11] Dragin N, Dalton TP, Miller ML, et al. For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential[J]. J Biol Chem. 2006, 281(27):18591-18600.
[12] Lim J, DeWitt JC, Sanders RA, et al. Suppression of endogenous antioxidant enzymes by 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in chicken liver during development[J]. Arch Environ Contam Toxicol. 2007, 52(4): 590-595.
[13] Jin MH, Hong CH, Lee HY, et al. Enhanced TGF-beta1 is involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress in C57BL/6 mouse testis[J]. Toxicol Lett. 2008, 178(3):202-209.
[14] Kubota F, Murakami T, Mogi K, et al. Cadherin-6 is required for zebrafish nephrogenesis during early development[J]. Int J Dev Biol. 2007, 51(2):123-129.
[15] Disanza A, Steffen A, Hertzog M, et al. Actin polymerization machinery: the finish line of signaling networks, the starting point of cellular movement[J]. Cell Mol Life Sci. 2005, 62(9):955-970.
[16] Ivetic A, Ridley AJ. Ezrin/radixin/moesin proteins and Rho GTPase signalling in leucocytes[J]. Immunology. 2004, 112(2):165-176.
[17] Zhu YZ, Robert WZ, Margaret EF, et a1. Primary cell culture for embryonic cardiacmyocytes of mexican axolotl and distribution of desmin and vimentin[J]. Chinese J Histochemistry and cytochemistry J.1999, 8(1):110-114.
[18] Chen CL, Huang SS, Huang JS. Cholesterol modulates cellular TGF-beta responsiveness by altering TGF-beta binding to TGF-beta receptors[J]. J Cell Physiol. 2008, 215(1):223-233.
[19] Blaney Davidson EN, van der Kraan PM, van den Berg WB. TGF-beta and osteoarthritis[J]. Osteoarthritis Cartilage. 2007, 15(6):597-604.
[20] Niculescu-Duvaz I, Phanish MK, Colville-Nash P, et al. The TGFbeta1-induced fibronectin in human renal proximal tubular epithelial cells is p38 MAP kinase dependent and Smad independent[J]. Nephron Exp Nephrol. 2007, 105(4):e108-116.
[21] Diamond JR. Macrophages and progressive renal disease in experimental hydronephrosis[J]. Am J Kidney Dis. 1995, 26(1):133-140.
[22] Kleeff J, Korc M. Up-regulation of transforming growth factor (TGF)-beta receptors by TGF-beta1 in COLO-357 cells[J]. J Biol Chem. 1998, 273(13): 7495-7500.
[23] Montero-Hadjadje M, Vaingankar S, Elias S, et al. Chromogranins A and B and secretogranin II: evolutionary and functional aspects[J]. Acta Physiol (Oxf). 2008, 192(2):309-324.
[24] Hu SS, Fontaine F, Kelly B, et al. Nutritional depletion in staged spinal reconstructive surgery. The effect of total parenteral nutrition[J]. Spine. 1998, 23(12): 1401-1405.
[25] Abbott BD, Morgan KS, Birnbaum LS, et al. TCDD alters the extracellular matrix and basal lamina of the fetal mouse kidney[J]. Teratology. 1987, 35(3):335-344.
[26] Kralova A, Svetlikova M, Madar J, et al. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study[J]. Reprod Biol Endocrinol. 2008 Jul 2;6:27.
[27] Chu R, Lim H, Brumfield L, et al. Protein profiling of mouse livers with peroxisome proliferator-activated receptor alpha activation[J]. Mol Cell Biol. 2004, 24(14): 6288-6297.
[28] Kim EK, Jang WH, Ko JH, et al. Lipase and its modulator from Pseudomonas sp. strain KFCC 10818: proline-to-glutamine substitution at position 112 induces formation of enzymatically active lipase in the absence of the modulator[J]. J Bacteriol. 2001, 183(20):5937-5941.
[1] Ciolino HP, Daschner PJ, Yeh GC.Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially[J]. Biochem J. 1999, 340 ( Pt 3):715-722.
[2] Vásquez-Garzón VR, Arellanes-Robledo J, García-Román R, et al. Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism[J]. Free Radic Res. 2009, 43(2):128-137.
[3] Chaudhary A, Pechan T, Willett KL.Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines[J].Toxicol Appl Pharmacol. 2007, 220(2):197-210.
[4] Jang JY, Shin S, Choi BI, et al. Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero[J]. Reprod Toxicol. 2007, 24(3-4):303-309.
[5] Lee YK, Park SY, Kim YM, et al.AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin[J]. Exp Mol Med. 2009, 41(3):201-207.
[6] Rivera L, Morón R, Sánchez M, et al.Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats[J].Obesity (Silver Spring). 2008, 16(9):2081-2087.
[7] Wang L, Tu YC, Lian TW, et al.Distinctive antioxidant and antiinflammatory effects of flavonols[J]. J Agric Food Chem. 2006, 54(26):9798-9804.
[8] Hubbard GP, Wolffram S, de Vos R, et al.Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study[J]. Br J Nutr. 2006, 96(3):482-488.
[9] Zhang S, Qin C, Safe SH. Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context[J]. Environ Health Perspect. 2003, 111(16):1877-1882.
[10] Mandal PK. Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology[J]. J Comp Physiol [B]. 2005, 175(4):221-230.
[11] Gouédard C, Barouki R, Morel Y.Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism[J]. Mol Cell Biol. 2004, 24(12):5209-5222.
[12] Amakura Y, Tsutsumi T, Sasaki K, et al. Influence of food polyphenols on aryl hydrocarbon receptor-signaling pathway estimated by in vitro bioassay[J]. Phytochemistry. 2008, 69(18):3117-3130.
[13] Jang JY, Park D, Shin S, et al. Antiteratogenic effect of resveratrol in miceexposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Eur J Pharmacol. 2008, 591(1-3):280-283.
[14] de Forni M, Chabot GG, Armand JP, et al. Phase I and pharmacology study of flavone acetic acid administered two or three times weekly without alkalinization[J]. Cancer Chemother Pharmacol. 1995, 35(3):219-224.
[15] Leung HW, Kerger BD, Paustenbach DJ, et al. Concentration and age-dependent elimination kinetics of polychlorinated dibenzofurans in Yucheng and Yusho patients[J]. Toxicol Ind Health. 2007, 23(8):493-501.
[16] Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties[J]. Food Chem Toxicol. 2007, 45(11):2179–2205.
[1]肖东,顾振纶,朱寿彭.槲皮索的抗肿瘤作用与相关基因的调控[J].中国野生植物资源. 1996, (4):5-8.
[2] Graefe EU, Derendorf H, Veit M. Pharmacokinetics and bioavailability of the flavonol quercetin in humans[J]. Int J Clin Pharmacol Ther. 1999, 37(5):219–233.
[3] Wu TH, Yen FL, Lin LT, et al. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticle[J]s. Int J Pharm. 2008,346(1-2):160–168.
[4] Walle T, Otake Y, Walle UK, et al. Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption[J]. J Nutr. 2000, 130(11):2658–2661.
[5] Walle T, Walle UK, Halushka PV. Carbon dioxide is the major metabolite of quercetin in humans[J]. J Nutr. 2001, 131(10):2648–2652.
[6] Conquer JA, Maiani G, Azzini E, et al. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects[J]. J Nutr. 1998, 128(3):593–597.
[7] Hollman PC, vd Gaag M, Mengelers MJ, et al. Absorption and disposition kinetics of the dietary antioxidant quercetin in man[J]. Free Radic Biol Med. 1996, 21(5):703–707.
[8] Spencer JP, Kuhnle GG, Williams RJ, et al. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites[J]. Biochem J. 2003, 372(Pt 1):173–181.
[9] O’Leary KA, Day AJ, Needs PW, et al. Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human beta-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multiresistant protein 2 (MRP2) in flavonoid metabolism[J]. Biochem Pharmacol. 2003, 65(3):479–491.
[10] Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical[J]. Eur J Pharmacol. 2008, 585(2-3):325–337.
[11] Loke WM, Proudfoot JM, McKinley AJ, et al. Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation[J]. J Agric Food Chem. 2008, 56(10):3609–3615.
[12] Shutenko Z, Henry Y, Pinard E, et al. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion[J]. Biochem Pharmacol. 1999, 57(2):199–208.
[13] Huk I, Brovkovych V, Nanobash Vili J, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study[J]. Br J Surg. 1998, 85(8):1080–1085.
[14] Bindoli A, Valente M, Cavallini L. Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity[J]. Pharmacol Res Commun. 1985, 17(9):831–839.
[15] Zhu JX, Wang Y, Kong LD, et al. Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver[J]. J Ethnopharmacol. 2004, 93(1):133–140.
[16] Soundararajan R, Wishart AD, Rupasinghe HP, et al. Quercetin 3-glucoside protects neuroblastoma (SH-SY5Y) cells in vitro against oxidative damage by inducing sterol regulatory element-binding protein-2-mediated cholesterol biosynthesis[J]. J Biol Chem. 2008, 283(4):2231–2245.
[17] Romero M, Jiménez R, Sánchez M, et al. Quercetin inhibits vascular superoxide production induced by endothelin-1: role of NADPH oxidase, uncoupled eNOS and PKC[J]. Atherosclerosis. 2009, 202(1):58-67.
[18] Fanning MJ, Macander P, Drzewiecki G, et al. Quercetin inhibits anaphylactic contraction of guinea pig ileum smooth muscle[J]. Int Arch AllergyAppl Immunol. 1983, 71(4):371–373.
[19] Pearce FL, Befus AD, Bienenstock J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells[J]. J Allergy Clin Immunol. 1984, 73(6):819–823.
[20] Kimata M, Shichijo M, Miura T, et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells[J]. Clin Exp Allergy. 2000, 30(4):501–508.
[21] Kempuraj D, Castellani ML, Petrarca C, et al. Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line[J]. Clin Exp Med. 2006, 6(4):150–156.
[22] Shaik YB, Castellani ML, Perrella A, et al. Role of quercetin (a natural herbal compound) in allergy and inflammation[J]. J Biol Regul Homeost Agents. 2006, 20(3-4):47–52.
[23] Bureau G, LongpréF, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation[J]. J Neurosci Res. 2008, 86(2):403–410.
[24] Kumazawa Y, Kawaguchi K, Takimoto H. Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha[J]. Curr Pharm Des. 2006, 12(32):4271–4279.
[25] H?m?l?inen M, Nieminen R, Vuorela P, et al. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages[J]. Mediators Inflamm. 2007:45673.
[26] Lee KW, Kang NJ, Heo YS, et al. Raf and MEK protein kinases are direct molecular targets for the chemopreventive effect of quercetin, a major flavonol in red wine[J]. Cancer Res. 2008, 68(3):946–955.
[27] Ono K, Nakane H, Fukushima M, et al. Differential inhibitory effects of various flavonoids on the activities of reverse transcriptase and cellular DNA and RNA polymerases[J]. Eur J Biochem. 1990, 190(3):469–476.
[28] Spedding G, Ratty A, Middleton E Jr. Inhibition of reverse transcriptases byflavonoids[J]. Antiviral Res. 1989, 12(2):99–110.
[29] Nezanov N, Kondratova A, Chumakov KM, et al. Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin[J]. DNA Cell Biol. 2008, 27(4):191–198.
[30] Davis JM, Murphy EA, McClellan JL, et al. Quercetin reduces susceptibility to influenza infection following stressful exercise[J]. Am J Physiol Regul Integr Comp Physiol. 2008, 295(2):R505–R509.
[31] Gatto MT, Falcocchio S, Grippa E, et al. Antimicrobial and antilipase activity of quercetin and its C2-C16 3-O-acyl-esters[J]. Bioorg Med Chem. 2002, 10(2):269–272.
[32] Li M, Xu Z. Quercetin in a lotus leaves extract may be responsible forantibacterial activity[J]. Arch Pharm Res. 2008, 31(5):640–644.
[33] Plaper A, Golob M, Hafner I, et al. Characterization of quercetin binding site on DNA gyrase[J]. Biochem Biophys Res Commun. 2003, 306(2):530–536.
[34] González-Segovia R, Quintanar JL, Salinas E, et al. Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig[J]. J Gastroenterol. 2008, 43(6):441–447.
[35] Sheu JR, Hsiao G, Chou PH, et al. Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the flavonol quercetin, in human platelets[J]. J Agric Food Chem. 2004, 52(14):4414–4418.
[36] Hubbard GP, Stevens JM, Cicmil M, et al. Quercetin inhibits collagenstimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway[J]. J Thromb Haemost. 2003, 1(5):1079–1088.
[37] Pignatelli P, Di Santo S, Carnevale R, Violi F. The polyphenols quercetin and catechin synergize in inhibiting platelet CD40L expression[J]. Thromb Haemost. 2005, 94(4):888–889.
[38] Fan PS, Gu ZL, Liang ZQ. Effect of quercetin on adhesion of platelets to microvascular endothelial cells in vitro[J]. Acta Pharmacol Sin. 2001, 22(9):857–860.
[39] Ko WC, Wang HL, Lei CB, et al. Mechanisms of relaxant action of 3-Omethylquercetin in isolated guinea pig trachea[J]. Planta Med. 2002, 68(1):30–35.
[40] Dell’Agli M, MaschiO, Galli GV, et al. Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase[J]. Br J Nutr. 2008, 99(5):945–951.
[41] Gryglewski RJ, Korbut R, Robak J, et al. On the mechanism of antithrombotic action of flavonoids[J]. Biochem Pharmacol. 1987, 36(3):317–322.
[42] Rosenkranz S, Caglayan E, Erdmann E. Novel indications for phosphodiesterase type 5 inhibitors[J]. Med Klin (Munich). 2007, 102(8):617–630.
[43] Palmer MJ, Bell AS, Fox DN, et al. Design of second generation phosphodiesterase 5 inhibitors[J]. Curr Top Med Chem. 2007, 7(4):405–419.
[44] Lines TC, Ono M. FRS 1000, an extract of red onion peel, strongly inhibits phosphodiesterase 5A (PDE 5A) [J]. Phytomedicine. 2006, 13(4):236–239.
[45] Xin ZC, Kim EK, Lin CS, et al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities[J]. Asian J Androl. 2003, 5(1):15–18.
[46] Wang H, Liu Y, Huai Q, et al. Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development[J]. J Biol Chem. 2006, 281(30):21469–21479.
[47] Varma SD, Mikuni I, Kinoshita JH. Flavonoids as inhibitors of lens aldose reductase[J]. Science. 1975, 188(4194):1215–1216.
[48] Bron AJ, Sparrow J, Brown NA, et al. The lens in diabetes[J]. Eye. 1993, 7(Pt 2): 260–275.
[49] Schlachterman A, Valle F, Wall KM, et al. Combined resveratrol, quercetin,and catechin treatment reduces breast tumor growth in a nude mouse model[J].Transl Oncol. 2008, 1(1):19–27.
[50] Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin[J].Cancer Lett. 2008, 269(2):315-325.
[51] Yamashita N, Kawanishi S. Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin[J]. Free Radic Res. 2000, 33(5):623–633.
[52] Aherne SA, O’Brien NM. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells[J]. Free Radic Biol Med. 2000, 29(6):507–514.
[53] Psahoulia FH, Drosopoulos KG, Doubravska L, et al. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts[J]. Mol Cancer Ther. 2007, 6(9):2591–2599.
[54] Chen W, Wang X, Zhuang J, et al. Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in nonsmall cell lung cancer cells[J]. Carcinogenesis. 2007, 28(10): 2114–2121.
[55] Kim YH, Lee YJ. TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation[J]. J Cell Biochem. 2007, 100(4):998–1009.
[56] Brusselmans K, Vrolix R, Verhoeven G, et al. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity[J]. J Biol Chem. 2005, 280(7):5636–5645.
[57] Xing N, Chen Y, Mitchell SH, et al. Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells[J]. Carcinogenesis. 2001, 22(3):409–414.
[58] Morris JD, Pramanik R, Zhang X, et al. Selenium- or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity[J]. Cancer Lett. 2006, 239(1):111–122.
[59] Katske F, Shoskes DA, Sender M, et al. Treatment of interstitial cystitis with a quercetin supplement[J]. Tech Urol. 2001, 7(1):44–46.
[60] Shoskes DA, Zeitlin SI, Shahed A, et al. Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebocontrolled trial. Urology[J]. 1999, 54(6):960–963.
[61] Kim H, Kong H, Choi B, et al. Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease[J]. Pharm Res. 2005, 22(9):1499–1509.
[62] Rao CV, Vijayakumar M. Effect of quercetin, flavonoids and alpha-tocopherol, an antioxidant vitamin on experimental reflux oesophagitis in rats[J]. Eur J Pharmacol. 2008, 589(1-3):233–238.
[63] Perez-Vizcaino F, Duarte J, Andriantsitohaina R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols[J]. Free Radic Res. 2006, 40(10):1054–1065.
[64] Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects[J]. J Nutr. 2007, 137(11):2405–2411.
[65] Chopra M, Fitzsimons PE, Strain JJ, et al. Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affecting plasma antioxidant vitamin and carotenoid concentrations[J]. Clin Chem. 2000, 46(8 Pt 1):1162–1170.
[66] Hubbard GP, Wolffram S, Lovegrove JA, et al. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagenstimulated platelet activation pathway in humans[J]. J Thromb Haemost. 2004, 2(12):2138–2145.
[67] Hubbard GP, Wolffram S, de Vos R, et al. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study[J]. Br J Nutr. 2006, 96(3):482–488.
[68] Mardla V, Kobzar G, Samel N. Potentiation of antiaggregating effect of prostaglandins by alpha-tocopherol and quercetin. Platelets[J]. 2004,15(5):319–324.
[69] Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol[J]. 2006, 4(8):1035–1038.
[70] Valensi P, Le Devehat C, Richard JL, et al. A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy[J]. A preliminary report. J Diabetes Complications. 2005, 19(5):247–253.
[71] Okamoto T. Safety of quercetin for clinical application (review) [J]. Int J Mol Med. 2005, 16(2):275–278.
[72] Utesch D, Feige K, Dasenbrock J, et al. Evaluation of the potential in vivo genotoxicity of quercetin[J]. Mutat Res. 2008, 654(1):38–44.
[73] Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties[J]. Food Chem Toxicol. 2007, 45(11):2179–2205.
[1] Belarmino JM, Kogan BA. Management of neonatal hydronephrosis[J].Early Hum Dev. 2006, 82(1):9-14.
[2] Iura T, Makinota S, Miyazaki S, et a1. Prenatal diagnosis of the hemodynamics of fetal renal disease by color Doppler ultrasound[J]. Fetal Diagn Ther. 2003, 18(3): 148-153.
[3] Coplen DE. Prenatal intervention for hydronephrosis[J]. J Urol. 1997, 157(6): 2270-2277.
[4] Brugger PC, Prayer D. Fetal abdominal magnetic resonance imaging[J]. Eur J Radiol. 2006, 57(2): 278-293.
[5] Fernbach SK, Maizels M, Co nway JJ. Ultrasound grading of hydronephrosis: Introduction to the system used by the society for fetal urology[J]. Pediatr Radiol. 1993, 23(6):478-480.
[6] Grignon A, Filion R, Filiatrault D, et a1. Urinary dilatation in utero:Classification and clinical applications[J]. Radiology. 1986, 160(3):645-647.
[7] Woodward M, Frank D.Postnatal management of antenatal hydronephrosis[J]. BJU Int,2002,89 (2):149-156.
[8] CoaeviHe JE, Gray DL, Grane JP. Congenital hydronephrosis: Correlmion of fetal Ultrasonographic findings with infant outcome[J]. Am J 0bstet Gynecol. 1991, 165(2):384-388.
[9] Lee RS, Cendron M, Kinnamon DD, et al. Antenatal hydronephrosis as a predictor of postnatal outcome: a meta-analysis[J]. Pediatrics. 2006,118(2): 586-593.
[10] Pates JA, Dashe JS. Prenatal diagnosis and management of hydronephrosis[J]. Early Hum Dev. 2006, 82(1):3-8.
[11] Strand WR. Initial management of complex pediatric disorders:prime-belly syndrome,posterior urethral valves[J]. Urol Clin North Am. 2004, 31(3): 399-415.
[12] Suwanrath-KC, Limprasert P, Mitarnun W. Prenatal diagtosis of deletion of chromosome 6p,presenting with hydrops fetalis[J]. Prenat Diagn. 2004, 24(11):887-889.
[13] Tihy F, Lemieux X, Lemyre E. Complex chromosome rearranmgement and recombinant balanced translocation in a mother and a daughter with the same phenotypic abnormalities[J]. Am J Med Genet A. 2005, 135(3):317-3l9.
[14] Staebler M, Donner C, Van Regemorter N, et a1. Should determination of the karyotype be systematic for all malformations detected by obstetrical ultrasound[J]? Prenat Diagn. 2005, 25(7):567-573.
[15] Danzer E, Sydorak RM, Harrison MR, et al. Minimal access fetal surgery[J]. Eur J Obstet Gynecol Reprod Biol. 2003, 108(1):3-13.
[16] Choi SH. The role of fetal surgery in life threatening anomalies[J].Yonsei Med J. 2001, 42(6):681-685.
[17] Roth JA, Diamond DA. Prenatal hydronephrosis[J]. Curr Opin Pediatr. 2001, 13(2):138-141.
[18] Sydorak RM, Hirose S, Sandberg PL. Chorioamniotic membrane separation following fetal surgery[J]. J Perinat. 2002, 22(5): 407-410.
[19] Deprest JA, VAn Ballaer PP, Evrard VA, et al. Experience with fetoscopic cord ligation[J]. Eur J Obstet Gynecol Reprod Biol. 1998, 81(2):157-164.
[2] Belarmino JM, Kogan BA. Management of neonatal hydronephrosis[J]. Early Hum Dev.2006, 82(1):9-14.
[3] Woodward M, Frank D.Postnatal management of antenatal hydronephrosis[J]. BJU Int.2002, 89(2):149–156.
[4] Nishimura N, Matsumura F, Vogel CF, et al. Critical role of cyclooxygenase-2 activation in pathogenesis of hydronephrosis caused by lactational exposure of mice to dioxin[J]. Toxicol Appl Pharmacol. 2008, 231(3):374-383.
[5] Nishimura N, Yonemoto J, Nishimura H, et al. Localization of cytochrome P450 1A1 in a specific region of hydronephrotic kidney of rat neonates lactationally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Toxicology. 2006, 227(1-2): 117-126.
[6] Kransler KM, McGarrigle BP, Olson JR. Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig[J]. Toxicology. 2007, 229(3):214-225.
[7] Hung YC, Huang GS, Sava VM, et al. Protective effects of tea melanin against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity: antioxidant activity and aryl hydrocarbon receptor suppressive effect[J]. Biol Pharm Bull. 2006, 29(11): 2284-2291.
[8] Mimura J, Fujii-Kuriyama Y. Functional role of AhR in the expression of toxic effects by TCDD[J]. Biochim Biophys Acta. 2003, 1619(3):263-268.
[9] Ciolino HP, Daschner PJ, Yeh GC. Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially[J]. Biochem J. 1999, 340( Pt 3):715-722.
[10] Vásquez-Garzón VR, Arellanes-Robledo J, García-Román R, et al. Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism[J]. Free Radic Res. 2009, 43(2):128-137.
[1] Kransler KM, McGarrigle BP, Olson JR.Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig[J]. Toxicology. 2007, 229(3):214-225.
[2] Jang JY, Park D, Shin S, et al. Antiteratogenic effect of resveratrol in mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin.Eur J Pharmacol[J]. 2008, 591(1-3):280-283.
[3] Ishida T, Oshimo T, Nishimura A, et al. Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone[J]. Biol Pharm Bull. 2004, 27(9):1397-1402.
[4] Jang JY,Shin S,Choi BI,et al.Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero[J].Reprod Toxicol.2007, 24(3-4):303-309.
[5] Guerin F, Azoulay R, Berrebi D, et al.Partial unilateral ureteral obstruction in newborn mice: magnetic resonance imaging and pathology studies[J].J Urol. 2008, 179(4):1553-1563.
[6] Horton CE Jr,Davisson MT,Jacobs JB,et al.Congenital progressive hydrone-phrosis in mice: a new recessive mutation[J]. J Urol. 1988, 140(5 Pt 2): 1310-1315.
[7] McDill BW, Li SZ, Kovach PA, et al. Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation[J]. Proc Natl Acad Sci U S A. 2006, 103(18):6952-6957.
[8] Friedman J, Hoyer JR, McCormick B, et al. Congenital unilateral hydronephrosis in the rat[J]. Kidney Int. 1979, 15(5):567-571.
[9] Tauchi K, Kanehara H. Hypertension and the renin-angiotensin system in the congenital hydronephrosis rat with non-obstructive pelviureteric junction abnormalities[J]. Exp Nephrol. 1996, 4(1):60-64.
[10] Dawrant MJ, Giles S, Bannigan J, et al. Adriamycin produces a reproducible teratogenic model of vertebral, anal, cardiovascular, tracheal, esophageal, renal, and limb anomalies in the mouse[J]. J Pediatr Surg. 2007, 42(10):1652-1658.
[11] Haruyama N, Cho A, Kulkarni AB.Overview: engineering transgenic constructs and mice[J]. Curr Protoc Cell Biol. 2009 Mar;Chapter 19:Unit 19.10.
[12] Bryant PL,Reid LM,Schmid JE, et al. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on fetal mouse urinary tract epithelium in vitro[J]. Toxicology. 2001, 162(1):23-34.
[13] Bryant PL,Schmid JE,Fenton SE,et al.Teratogenicity of 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) in mice lacking the expression of EGF and/or TGF-alpha[J].Toxicol Sci.2001, 62(1):103-114.
[14]谢小志,蔡正林,张海燕,等.先天性肾盂输尿管连接处狭窄的临床病理分析[J].临床与实验病理学杂志. 2004, 20(3):379-380.
[1] Kawakami T, Ito T, Ohsako S,et al. Possible involvement of arylhydrocarbon receptor variants in TCDD-induced thymic atrophy and XRE-dependent transcriptional activity in Wistar Hannover GALAS rats[J]. J Toxicol Sci. 2009,34(2): 209-220.
[2] Mandal PK. Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology[J]. J Comp Physiol [B]. 2005,175(4):221-230.
[3] Westerink WM, Stevenson JC, Schoonen WG. Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition[J]. Arch Toxicol. 2008,82(12):909-921.
[4] Service RF. Proteomics. Can Celera do it again[J]? Science. 2000,287(5461): 2136-2138.
[5] Wasinger VC, Cordwell SJ, Cerpa-Poljak A, et al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis. 1995,16(7): 1090-1094.
[6] Kim SU, Hwang CN, Sun HN, et al. Peroxiredoxin I is an indicator of microglia activation and protects against hydrogen peroxide-mediated microglial death[J]. Biol Pharm Bull.2008, 31(5):820-825.
[7] Immenschuh S, Baumgart-Vogt E. Peroxiredoxins,oxidative stress, and cell proliferation[J]. Antioxid Redox Signal. 2005, 7(5-6):768-777.
[8] Lee YM, Park SH, Shin DI, et al. Oxidative modification of peroxiredoxin is associated with drug-induced apoptotic signaling in experimental models of Parkinson disease[J]. J Biol Chem. 2008, 283(15):9986-9998.
[9] Mu ZM, Yin XY, Prochownik EV. Pag, a putative tumor suppressor, interacts with the Myc Box II domain of c-Myc and selectively alters its biological function and target gene expression[J]. J Biol Chem. 2002, 277(45):43175-43184.
[10] Daly KA, Lefévre C, Nicholas K, et al. Characterization and expression of Peroxiredoxin 1 in the neonatal tammar wallaby (Macropus eugenii) [J]. Comp Biochem Physiol B Biochem Mol Biol. 2008, 149(1):108-119.
[11] Dragin N, Dalton TP, Miller ML, et al. For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential[J]. J Biol Chem. 2006, 281(27):18591-18600.
[12] Lim J, DeWitt JC, Sanders RA, et al. Suppression of endogenous antioxidant enzymes by 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in chicken liver during development[J]. Arch Environ Contam Toxicol. 2007, 52(4): 590-595.
[13] Jin MH, Hong CH, Lee HY, et al. Enhanced TGF-beta1 is involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress in C57BL/6 mouse testis[J]. Toxicol Lett. 2008, 178(3):202-209.
[14] Kubota F, Murakami T, Mogi K, et al. Cadherin-6 is required for zebrafish nephrogenesis during early development[J]. Int J Dev Biol. 2007, 51(2):123-129.
[15] Disanza A, Steffen A, Hertzog M, et al. Actin polymerization machinery: the finish line of signaling networks, the starting point of cellular movement[J]. Cell Mol Life Sci. 2005, 62(9):955-970.
[16] Ivetic A, Ridley AJ. Ezrin/radixin/moesin proteins and Rho GTPase signalling in leucocytes[J]. Immunology. 2004, 112(2):165-176.
[17] Zhu YZ, Robert WZ, Margaret EF, et a1. Primary cell culture for embryonic cardiacmyocytes of mexican axolotl and distribution of desmin and vimentin[J]. Chinese J Histochemistry and cytochemistry J.1999, 8(1):110-114.
[18] Chen CL, Huang SS, Huang JS. Cholesterol modulates cellular TGF-beta responsiveness by altering TGF-beta binding to TGF-beta receptors[J]. J Cell Physiol. 2008, 215(1):223-233.
[19] Blaney Davidson EN, van der Kraan PM, van den Berg WB. TGF-beta and osteoarthritis[J]. Osteoarthritis Cartilage. 2007, 15(6):597-604.
[20] Niculescu-Duvaz I, Phanish MK, Colville-Nash P, et al. The TGFbeta1-induced fibronectin in human renal proximal tubular epithelial cells is p38 MAP kinase dependent and Smad independent[J]. Nephron Exp Nephrol. 2007, 105(4):e108-116.
[21] Diamond JR. Macrophages and progressive renal disease in experimental hydronephrosis[J]. Am J Kidney Dis. 1995, 26(1):133-140.
[22] Kleeff J, Korc M. Up-regulation of transforming growth factor (TGF)-beta receptors by TGF-beta1 in COLO-357 cells[J]. J Biol Chem. 1998, 273(13): 7495-7500.
[23] Montero-Hadjadje M, Vaingankar S, Elias S, et al. Chromogranins A and B and secretogranin II: evolutionary and functional aspects[J]. Acta Physiol (Oxf). 2008, 192(2):309-324.
[24] Hu SS, Fontaine F, Kelly B, et al. Nutritional depletion in staged spinal reconstructive surgery. The effect of total parenteral nutrition[J]. Spine. 1998, 23(12): 1401-1405.
[25] Abbott BD, Morgan KS, Birnbaum LS, et al. TCDD alters the extracellular matrix and basal lamina of the fetal mouse kidney[J]. Teratology. 1987, 35(3):335-344.
[26] Kralova A, Svetlikova M, Madar J, et al. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study[J]. Reprod Biol Endocrinol. 2008 Jul 2;6:27.
[27] Chu R, Lim H, Brumfield L, et al. Protein profiling of mouse livers with peroxisome proliferator-activated receptor alpha activation[J]. Mol Cell Biol. 2004, 24(14): 6288-6297.
[28] Kim EK, Jang WH, Ko JH, et al. Lipase and its modulator from Pseudomonas sp. strain KFCC 10818: proline-to-glutamine substitution at position 112 induces formation of enzymatically active lipase in the absence of the modulator[J]. J Bacteriol. 2001, 183(20):5937-5941.
[1] Ciolino HP, Daschner PJ, Yeh GC.Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially[J]. Biochem J. 1999, 340 ( Pt 3):715-722.
[2] Vásquez-Garzón VR, Arellanes-Robledo J, García-Román R, et al. Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism[J]. Free Radic Res. 2009, 43(2):128-137.
[3] Chaudhary A, Pechan T, Willett KL.Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines[J].Toxicol Appl Pharmacol. 2007, 220(2):197-210.
[4] Jang JY, Shin S, Choi BI, et al. Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero[J]. Reprod Toxicol. 2007, 24(3-4):303-309.
[5] Lee YK, Park SY, Kim YM, et al.AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin[J]. Exp Mol Med. 2009, 41(3):201-207.
[6] Rivera L, Morón R, Sánchez M, et al.Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats[J].Obesity (Silver Spring). 2008, 16(9):2081-2087.
[7] Wang L, Tu YC, Lian TW, et al.Distinctive antioxidant and antiinflammatory effects of flavonols[J]. J Agric Food Chem. 2006, 54(26):9798-9804.
[8] Hubbard GP, Wolffram S, de Vos R, et al.Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study[J]. Br J Nutr. 2006, 96(3):482-488.
[9] Zhang S, Qin C, Safe SH. Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context[J]. Environ Health Perspect. 2003, 111(16):1877-1882.
[10] Mandal PK. Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology[J]. J Comp Physiol [B]. 2005, 175(4):221-230.
[11] Gouédard C, Barouki R, Morel Y.Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism[J]. Mol Cell Biol. 2004, 24(12):5209-5222.
[12] Amakura Y, Tsutsumi T, Sasaki K, et al. Influence of food polyphenols on aryl hydrocarbon receptor-signaling pathway estimated by in vitro bioassay[J]. Phytochemistry. 2008, 69(18):3117-3130.
[13] Jang JY, Park D, Shin S, et al. Antiteratogenic effect of resveratrol in miceexposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Eur J Pharmacol. 2008, 591(1-3):280-283.
[14] de Forni M, Chabot GG, Armand JP, et al. Phase I and pharmacology study of flavone acetic acid administered two or three times weekly without alkalinization[J]. Cancer Chemother Pharmacol. 1995, 35(3):219-224.
[15] Leung HW, Kerger BD, Paustenbach DJ, et al. Concentration and age-dependent elimination kinetics of polychlorinated dibenzofurans in Yucheng and Yusho patients[J]. Toxicol Ind Health. 2007, 23(8):493-501.
[16] Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties[J]. Food Chem Toxicol. 2007, 45(11):2179–2205.
[1]肖东,顾振纶,朱寿彭.槲皮索的抗肿瘤作用与相关基因的调控[J].中国野生植物资源. 1996, (4):5-8.
[2] Graefe EU, Derendorf H, Veit M. Pharmacokinetics and bioavailability of the flavonol quercetin in humans[J]. Int J Clin Pharmacol Ther. 1999, 37(5):219–233.
[3] Wu TH, Yen FL, Lin LT, et al. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticle[J]s. Int J Pharm. 2008,346(1-2):160–168.
[4] Walle T, Otake Y, Walle UK, et al. Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption[J]. J Nutr. 2000, 130(11):2658–2661.
[5] Walle T, Walle UK, Halushka PV. Carbon dioxide is the major metabolite of quercetin in humans[J]. J Nutr. 2001, 131(10):2648–2652.
[6] Conquer JA, Maiani G, Azzini E, et al. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects[J]. J Nutr. 1998, 128(3):593–597.
[7] Hollman PC, vd Gaag M, Mengelers MJ, et al. Absorption and disposition kinetics of the dietary antioxidant quercetin in man[J]. Free Radic Biol Med. 1996, 21(5):703–707.
[8] Spencer JP, Kuhnle GG, Williams RJ, et al. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites[J]. Biochem J. 2003, 372(Pt 1):173–181.
[9] O’Leary KA, Day AJ, Needs PW, et al. Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human beta-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multiresistant protein 2 (MRP2) in flavonoid metabolism[J]. Biochem Pharmacol. 2003, 65(3):479–491.
[10] Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical[J]. Eur J Pharmacol. 2008, 585(2-3):325–337.
[11] Loke WM, Proudfoot JM, McKinley AJ, et al. Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation[J]. J Agric Food Chem. 2008, 56(10):3609–3615.
[12] Shutenko Z, Henry Y, Pinard E, et al. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion[J]. Biochem Pharmacol. 1999, 57(2):199–208.
[13] Huk I, Brovkovych V, Nanobash Vili J, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study[J]. Br J Surg. 1998, 85(8):1080–1085.
[14] Bindoli A, Valente M, Cavallini L. Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity[J]. Pharmacol Res Commun. 1985, 17(9):831–839.
[15] Zhu JX, Wang Y, Kong LD, et al. Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver[J]. J Ethnopharmacol. 2004, 93(1):133–140.
[16] Soundararajan R, Wishart AD, Rupasinghe HP, et al. Quercetin 3-glucoside protects neuroblastoma (SH-SY5Y) cells in vitro against oxidative damage by inducing sterol regulatory element-binding protein-2-mediated cholesterol biosynthesis[J]. J Biol Chem. 2008, 283(4):2231–2245.
[17] Romero M, Jiménez R, Sánchez M, et al. Quercetin inhibits vascular superoxide production induced by endothelin-1: role of NADPH oxidase, uncoupled eNOS and PKC[J]. Atherosclerosis. 2009, 202(1):58-67.
[18] Fanning MJ, Macander P, Drzewiecki G, et al. Quercetin inhibits anaphylactic contraction of guinea pig ileum smooth muscle[J]. Int Arch AllergyAppl Immunol. 1983, 71(4):371–373.
[19] Pearce FL, Befus AD, Bienenstock J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells[J]. J Allergy Clin Immunol. 1984, 73(6):819–823.
[20] Kimata M, Shichijo M, Miura T, et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells[J]. Clin Exp Allergy. 2000, 30(4):501–508.
[21] Kempuraj D, Castellani ML, Petrarca C, et al. Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line[J]. Clin Exp Med. 2006, 6(4):150–156.
[22] Shaik YB, Castellani ML, Perrella A, et al. Role of quercetin (a natural herbal compound) in allergy and inflammation[J]. J Biol Regul Homeost Agents. 2006, 20(3-4):47–52.
[23] Bureau G, LongpréF, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation[J]. J Neurosci Res. 2008, 86(2):403–410.
[24] Kumazawa Y, Kawaguchi K, Takimoto H. Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha[J]. Curr Pharm Des. 2006, 12(32):4271–4279.
[25] H?m?l?inen M, Nieminen R, Vuorela P, et al. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages[J]. Mediators Inflamm. 2007:45673.
[26] Lee KW, Kang NJ, Heo YS, et al. Raf and MEK protein kinases are direct molecular targets for the chemopreventive effect of quercetin, a major flavonol in red wine[J]. Cancer Res. 2008, 68(3):946–955.
[27] Ono K, Nakane H, Fukushima M, et al. Differential inhibitory effects of various flavonoids on the activities of reverse transcriptase and cellular DNA and RNA polymerases[J]. Eur J Biochem. 1990, 190(3):469–476.
[28] Spedding G, Ratty A, Middleton E Jr. Inhibition of reverse transcriptases byflavonoids[J]. Antiviral Res. 1989, 12(2):99–110.
[29] Nezanov N, Kondratova A, Chumakov KM, et al. Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin[J]. DNA Cell Biol. 2008, 27(4):191–198.
[30] Davis JM, Murphy EA, McClellan JL, et al. Quercetin reduces susceptibility to influenza infection following stressful exercise[J]. Am J Physiol Regul Integr Comp Physiol. 2008, 295(2):R505–R509.
[31] Gatto MT, Falcocchio S, Grippa E, et al. Antimicrobial and antilipase activity of quercetin and its C2-C16 3-O-acyl-esters[J]. Bioorg Med Chem. 2002, 10(2):269–272.
[32] Li M, Xu Z. Quercetin in a lotus leaves extract may be responsible forantibacterial activity[J]. Arch Pharm Res. 2008, 31(5):640–644.
[33] Plaper A, Golob M, Hafner I, et al. Characterization of quercetin binding site on DNA gyrase[J]. Biochem Biophys Res Commun. 2003, 306(2):530–536.
[34] González-Segovia R, Quintanar JL, Salinas E, et al. Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig[J]. J Gastroenterol. 2008, 43(6):441–447.
[35] Sheu JR, Hsiao G, Chou PH, et al. Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the flavonol quercetin, in human platelets[J]. J Agric Food Chem. 2004, 52(14):4414–4418.
[36] Hubbard GP, Stevens JM, Cicmil M, et al. Quercetin inhibits collagenstimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway[J]. J Thromb Haemost. 2003, 1(5):1079–1088.
[37] Pignatelli P, Di Santo S, Carnevale R, Violi F. The polyphenols quercetin and catechin synergize in inhibiting platelet CD40L expression[J]. Thromb Haemost. 2005, 94(4):888–889.
[38] Fan PS, Gu ZL, Liang ZQ. Effect of quercetin on adhesion of platelets to microvascular endothelial cells in vitro[J]. Acta Pharmacol Sin. 2001, 22(9):857–860.
[39] Ko WC, Wang HL, Lei CB, et al. Mechanisms of relaxant action of 3-Omethylquercetin in isolated guinea pig trachea[J]. Planta Med. 2002, 68(1):30–35.
[40] Dell’Agli M, MaschiO, Galli GV, et al. Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase[J]. Br J Nutr. 2008, 99(5):945–951.
[41] Gryglewski RJ, Korbut R, Robak J, et al. On the mechanism of antithrombotic action of flavonoids[J]. Biochem Pharmacol. 1987, 36(3):317–322.
[42] Rosenkranz S, Caglayan E, Erdmann E. Novel indications for phosphodiesterase type 5 inhibitors[J]. Med Klin (Munich). 2007, 102(8):617–630.
[43] Palmer MJ, Bell AS, Fox DN, et al. Design of second generation phosphodiesterase 5 inhibitors[J]. Curr Top Med Chem. 2007, 7(4):405–419.
[44] Lines TC, Ono M. FRS 1000, an extract of red onion peel, strongly inhibits phosphodiesterase 5A (PDE 5A) [J]. Phytomedicine. 2006, 13(4):236–239.
[45] Xin ZC, Kim EK, Lin CS, et al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities[J]. Asian J Androl. 2003, 5(1):15–18.
[46] Wang H, Liu Y, Huai Q, et al. Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development[J]. J Biol Chem. 2006, 281(30):21469–21479.
[47] Varma SD, Mikuni I, Kinoshita JH. Flavonoids as inhibitors of lens aldose reductase[J]. Science. 1975, 188(4194):1215–1216.
[48] Bron AJ, Sparrow J, Brown NA, et al. The lens in diabetes[J]. Eye. 1993, 7(Pt 2): 260–275.
[49] Schlachterman A, Valle F, Wall KM, et al. Combined resveratrol, quercetin,and catechin treatment reduces breast tumor growth in a nude mouse model[J].Transl Oncol. 2008, 1(1):19–27.
[50] Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin[J].Cancer Lett. 2008, 269(2):315-325.
[51] Yamashita N, Kawanishi S. Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin[J]. Free Radic Res. 2000, 33(5):623–633.
[52] Aherne SA, O’Brien NM. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells[J]. Free Radic Biol Med. 2000, 29(6):507–514.
[53] Psahoulia FH, Drosopoulos KG, Doubravska L, et al. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts[J]. Mol Cancer Ther. 2007, 6(9):2591–2599.
[54] Chen W, Wang X, Zhuang J, et al. Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in nonsmall cell lung cancer cells[J]. Carcinogenesis. 2007, 28(10): 2114–2121.
[55] Kim YH, Lee YJ. TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation[J]. J Cell Biochem. 2007, 100(4):998–1009.
[56] Brusselmans K, Vrolix R, Verhoeven G, et al. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity[J]. J Biol Chem. 2005, 280(7):5636–5645.
[57] Xing N, Chen Y, Mitchell SH, et al. Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells[J]. Carcinogenesis. 2001, 22(3):409–414.
[58] Morris JD, Pramanik R, Zhang X, et al. Selenium- or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity[J]. Cancer Lett. 2006, 239(1):111–122.
[59] Katske F, Shoskes DA, Sender M, et al. Treatment of interstitial cystitis with a quercetin supplement[J]. Tech Urol. 2001, 7(1):44–46.
[60] Shoskes DA, Zeitlin SI, Shahed A, et al. Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebocontrolled trial. Urology[J]. 1999, 54(6):960–963.
[61] Kim H, Kong H, Choi B, et al. Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease[J]. Pharm Res. 2005, 22(9):1499–1509.
[62] Rao CV, Vijayakumar M. Effect of quercetin, flavonoids and alpha-tocopherol, an antioxidant vitamin on experimental reflux oesophagitis in rats[J]. Eur J Pharmacol. 2008, 589(1-3):233–238.
[63] Perez-Vizcaino F, Duarte J, Andriantsitohaina R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols[J]. Free Radic Res. 2006, 40(10):1054–1065.
[64] Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects[J]. J Nutr. 2007, 137(11):2405–2411.
[65] Chopra M, Fitzsimons PE, Strain JJ, et al. Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affecting plasma antioxidant vitamin and carotenoid concentrations[J]. Clin Chem. 2000, 46(8 Pt 1):1162–1170.
[66] Hubbard GP, Wolffram S, Lovegrove JA, et al. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagenstimulated platelet activation pathway in humans[J]. J Thromb Haemost. 2004, 2(12):2138–2145.
[67] Hubbard GP, Wolffram S, de Vos R, et al. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study[J]. Br J Nutr. 2006, 96(3):482–488.
[68] Mardla V, Kobzar G, Samel N. Potentiation of antiaggregating effect of prostaglandins by alpha-tocopherol and quercetin. Platelets[J]. 2004,15(5):319–324.
[69] Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol[J]. 2006, 4(8):1035–1038.
[70] Valensi P, Le Devehat C, Richard JL, et al. A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy[J]. A preliminary report. J Diabetes Complications. 2005, 19(5):247–253.
[71] Okamoto T. Safety of quercetin for clinical application (review) [J]. Int J Mol Med. 2005, 16(2):275–278.
[72] Utesch D, Feige K, Dasenbrock J, et al. Evaluation of the potential in vivo genotoxicity of quercetin[J]. Mutat Res. 2008, 654(1):38–44.
[73] Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties[J]. Food Chem Toxicol. 2007, 45(11):2179–2205.
[1] Belarmino JM, Kogan BA. Management of neonatal hydronephrosis[J].Early Hum Dev. 2006, 82(1):9-14.
[2] Iura T, Makinota S, Miyazaki S, et a1. Prenatal diagnosis of the hemodynamics of fetal renal disease by color Doppler ultrasound[J]. Fetal Diagn Ther. 2003, 18(3): 148-153.
[3] Coplen DE. Prenatal intervention for hydronephrosis[J]. J Urol. 1997, 157(6): 2270-2277.
[4] Brugger PC, Prayer D. Fetal abdominal magnetic resonance imaging[J]. Eur J Radiol. 2006, 57(2): 278-293.
[5] Fernbach SK, Maizels M, Co nway JJ. Ultrasound grading of hydronephrosis: Introduction to the system used by the society for fetal urology[J]. Pediatr Radiol. 1993, 23(6):478-480.
[6] Grignon A, Filion R, Filiatrault D, et a1. Urinary dilatation in utero:Classification and clinical applications[J]. Radiology. 1986, 160(3):645-647.
[7] Woodward M, Frank D.Postnatal management of antenatal hydronephrosis[J]. BJU Int,2002,89 (2):149-156.
[8] CoaeviHe JE, Gray DL, Grane JP. Congenital hydronephrosis: Correlmion of fetal Ultrasonographic findings with infant outcome[J]. Am J 0bstet Gynecol. 1991, 165(2):384-388.
[9] Lee RS, Cendron M, Kinnamon DD, et al. Antenatal hydronephrosis as a predictor of postnatal outcome: a meta-analysis[J]. Pediatrics. 2006,118(2): 586-593.
[10] Pates JA, Dashe JS. Prenatal diagnosis and management of hydronephrosis[J]. Early Hum Dev. 2006, 82(1):3-8.
[11] Strand WR. Initial management of complex pediatric disorders:prime-belly syndrome,posterior urethral valves[J]. Urol Clin North Am. 2004, 31(3): 399-415.
[12] Suwanrath-KC, Limprasert P, Mitarnun W. Prenatal diagtosis of deletion of chromosome 6p,presenting with hydrops fetalis[J]. Prenat Diagn. 2004, 24(11):887-889.
[13] Tihy F, Lemieux X, Lemyre E. Complex chromosome rearranmgement and recombinant balanced translocation in a mother and a daughter with the same phenotypic abnormalities[J]. Am J Med Genet A. 2005, 135(3):317-3l9.
[14] Staebler M, Donner C, Van Regemorter N, et a1. Should determination of the karyotype be systematic for all malformations detected by obstetrical ultrasound[J]? Prenat Diagn. 2005, 25(7):567-573.
[15] Danzer E, Sydorak RM, Harrison MR, et al. Minimal access fetal surgery[J]. Eur J Obstet Gynecol Reprod Biol. 2003, 108(1):3-13.
[16] Choi SH. The role of fetal surgery in life threatening anomalies[J].Yonsei Med J. 2001, 42(6):681-685.
[17] Roth JA, Diamond DA. Prenatal hydronephrosis[J]. Curr Opin Pediatr. 2001, 13(2):138-141.
[18] Sydorak RM, Hirose S, Sandberg PL. Chorioamniotic membrane separation following fetal surgery[J]. J Perinat. 2002, 22(5): 407-410.
[19] Deprest JA, VAn Ballaer PP, Evrard VA, et al. Experience with fetoscopic cord ligation[J]. Eur J Obstet Gynecol Reprod Biol. 1998, 81(2):157-164.
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