亚硒酸钠对糖尿病肾病大鼠肾脏保护作用机制研究
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摘要
背景:随着人们生活水平的提高和生活模式的改变,糖尿病血管并发症发生率逐年上升,糖尿病肾病(DN)是糖尿病(DM)微血管并发症之一,近年来发病率逐年升高,已成为终末期肾病(ESRD)的首位病因,同时也是DM的严重并发症和主要死亡原因之一。一旦出现持续蛋白尿,则病情不可逆转,最终发展成终末期肾衰竭,只能靠透析和替代治疗维持生命。所以早期干预,阻止或延缓糖尿病肾病病程进展,极为必要。
硒是机体必需的微量元素之一,是谷胱甘肽过氧化物酶必需的结构成分,谷胱甘肽过氧化物酶的主要功能是清除体内过氧化物,维持膜系统的完整性。近年来研究发现硒具有降低血糖和调控胰岛素介导的代谢过程等拟胰岛素作用。对糖尿病鼠补充硒不仅可预防氧化应激,而且也可防止肾脏损伤,同时能改善葡萄糖内环境和增强外周组织对胰岛素的敏感性。但硒在防治糖尿病肾病中的作用及机制,国内外报道甚少,所以其在糖尿病肾病中的防治效果和相关分子机制值得进一步探讨。
第一部分亚硒酸钠对糖尿病肾病大鼠基本状况和肾脏病变的干预作用
目的:通过链尿佐菌素法及长期高脂饮食诱导构建糖尿病肾病模型,并长期给予亚硒酸钠口服治疗,探讨硒对糖尿病肾病大鼠基本状况的改善和肾脏病变的延缓作用,评价硒防治糖尿病肾病的效果。
方法:以链尿佐菌素55mg/kg体重剂量一次性腹腔注射及长期高脂饮食喂养构建糖尿病肾病模型,试验设空白组(N)、糖尿病对照组(DM)和亚硒酸钠干预组(DM-Se),干预组给予亚硒酸钠治疗。各组大鼠分笼喂养,实验期间自由进食、进水,自然照明,室温20℃-28℃,均不给与胰岛素和降糖药。喂养10周后,观察各组大鼠全身基本状况。用代谢笼准确收集24小时尿量,用试剂盒检测尿24小时白蛋白和尿肌酐。处死大鼠,腹主动脉取血清,测定血肌酐、血糖等指标。取双肾,去除肾包膜,用冷生理盐水灌洗,同时观察肾脏大小、颜色、质地,称双肾重量。快速切取小块肾皮质组织,4%戊二醛固定,制电镜切片扫描电镜观察超微结构。切取肾脏组织,4%多聚甲醛固定,制石蜡切片HE染色光镜下观察病理改变。所有数据用SPSS11.0软件包分析统计学意义。
结果:
1.药物干预组大鼠较模型对照组全身基本状况明显改善,血糖、肾重/体重比值无明显变化,而血肌酐、尿24小时白蛋白等指标明显改善。
2.干预组大鼠肾脏光镜下组织形态病理变化和电镜下超微结构均较模型对照组明显改善。
结论:
1.亚硒酸钠能显著改善糖尿病肾病大鼠的全身状况。
2.亚硒酸钠能延缓糖尿病肾病大鼠的肾脏病变。
第二部分亚硒酸钠对糖尿病肾病大鼠肾脏p38MAPK、nephrin、adiponectin表达的影响
目的:通过链尿佐菌素法及长期高脂饮食诱导构建糖尿病肾病模型,并长期给予亚硒酸钠口服治疗,探讨硒对糖尿病肾病大鼠肾脏p38MAPK、nephrin、adiponectin表达的影响,从而研究硒在防治糖尿病肾病中的作用机制。
方法:以链尿佐菌素55mg/kg体重剂量一次性腹腔注射及长期给予高脂饮食喂养构建糖尿病肾病模型,试验设空白组(N)、糖尿病对照组(DM)和亚硒酸钠干预组(DM-Se),干预组给予亚硒酸钠治疗。各组大鼠分笼喂养,实验期间自由进食、进水,自然照明,室温20℃-28℃,均不给与胰岛素和降糖药。喂养10周后,处死大鼠,取双肾,去除肾包膜,用冷生理盐水灌洗,同时观察肾脏大小、颜色、质地,称双肾重量。切取肾脏组织,4%多聚甲醛固定,制石蜡切片免疫组化分析p38MAPK、nephrin、adiponectin蛋白表达。切取双肾组织投入液氮冻存,组织匀浆提取总RNA和总蛋白分别用PCR法和Western blotting法分析p38MAPK、nephrin、adiponectin mRNA表达和蛋白表达。相关软件分析图片,获得数据。所有数据用SPSS11.0软件包分析统计学意义。
结果:
1、干预组p38 MAPK mRNA及蛋白表达均较模型对照组降低,但较空白组高。
2、干预组nephrin mRNA及蛋白表达均较模型对照组增加,但较空白组低。
3、干预组adiponectin mRNA及蛋白表达量均较空白组明显增加,较模型对照组增加;模型对照组adiponectin mRNA及蛋白的表达量均较空白组增加。
结论:亚硒酸钠能促进脂联素、nephrin表达,抑制P38MAPK表达,可能与其抑制氧化应激、增加外周组织对胰岛素敏感性,从而改善糖尿病肾脏病变有关。
Background: With the raising of people’s life level and the changing of people’s life style, the rate of diabetic vascular complications is ascending year by year. Diabetic nephropathy is one of the diabetic microvascular complications, and it’s incidence rate is rising in recent years, and it has become the prime cause of End Stage Renal Disease (ESRD). It is one of the serious complications and main death cause of Diabetes mellitus(DM) too. Once emerging persistent proteinuria, the disease should not be reverted, which would develop end stage renal disease eventually. The patients survive only depend on dialysis and vicariousness treatment. So it is important to interfere in earlier period of the disease for delaying the disease process.
Selenium is one of the essential trace element of organism, and it consists in glutathione peroxidase.It’s main function is cleaning organism endoperoxide and keeping up the integrity of membrane system.It is discovered that selenite can imitate insulin to decrease serum glucose and regulate metabolic process mediated by insulin. To supplement selenium for diabetic rats not only protect oxidative stress , but also prevent kindey injury. Simultaneously, it can improve glucose internal environment and the sensitivity of periphery tissue toward insulin. In diabetic nephropathy, selenium intervention effect and molecule mechanism is less reported in internal and overseas, so it is really worth studying.
PART ONE THE EFFECT OF SELENITE ON BASIC CONDITIONS AND PATHOLOGICAL CHANGES OF DIABETIC NEPHROPATHY RATS
Objective: Diabetic nephropathy rat models were established by injecting streptozocin intraperitoneally and feeded high fat diet longly and were treated by oral medication selenite longly.The study would investigate the influence of sodium selenite on basic conditions and pathological changes in kidney of diabetic nephropathy rats, so as to estimate the effect of sodium selenite preventing diabetic nephropathy.
Methods: Diabetic nephropathy rat models were established by feeded high lipid diet and high consistency sucrose and injected intraperitoneally a single streptozocin (STZ) in a dose of 55 mg/kg for the rats. Three different groups of the rats were employed: control group, diabetic nephropathy group and selenite-treated group. Temperature were kept in a 20°C -28°C range. All rats were fed by separate cages, the food and water were ingested without limitation, natural illumination.All rats were not gave insulin and hypoglycemic agent in the whole process.After 10 weeks, the conditions of rats were observed. 24 hours’urine of the rats was collected by metabolic cage,which was used for detecting 24 hours’albumin and urine creatinine by kit. Rats were killed and serum was obtained from abdominal aorta, which was used to detect serum creatinine and serum glucose. Cut the kindey,cleaned the kindey amicula then douched the kindey by cool normal saline.The size、colour、texture and the weight of kindey were observed.The tablet renal cortex tissue was cut quickly and fixed with 4% glutaral to observe the fine structure by scanning electron microscope. Part of renal cortex tissue were fixed with 4% paraformaldehyde to make paraffin section which stained with HE to show kidney pathological changes by light microscope. All data were dealt with SPSS11.0 statistical software.
Results: 1. The basic conditions of selenite-treated group were significant better than diabetic nephropathy group. Kindey/body weight and Serum glucose had no difference between selenite-treated group and diabetic nephropathy group, but there were great differences for Serum creatinine and 24 hours urinary albumin. 2. The pathological changes by light microscope and fine structure changes by electron microscope in kindey of selenite-treated group were better than diabetic nephropathy group.
Conclusion: 1.Selenite can greatly improve the general body state of diabetic nephropathy rats.
2.Selenite can delay the kindey pathological changes of diabetic nephropathy rats
PART TWO THE INFLUENCE OF SELENITE ON p38MAPK、NEPHRIN、ADIPONECTIN EXPRESSION IN KIDNEY OF DIABETIC NEPHROPATHY RATS
Objective: Diabetic nephropathy rat models were established by injecting streptozocin intraperitoneally and feeded high fat diet longly and were treated by oral medication selenite longly.The study would evaluate the effect of sodium selenite on expression of p38MAPK、nephrin、adiponectin, so as to study its molecule mechanism in DN.
Methods:Diabetic nephropathy rat models were established by feeded high lipid diet and high consistency sucrose and injected intraperitoneally a single streptozocin (STZ) in a dose of 55 mg/kg for the rats. Three different groups of the rats were employed: control group, diabetic nephropathy group and selenite-treated group. Temperature were kept in a 20°C-28°C range. All rats were fed by separate cages, the food and water were ingested without limitation, natural illumination.All rats were not gave insulin and hypoglycemic agent in the whole process.After 10 weeks, the conditions of rats were observed. 24 hours’urine of the rats was collected by metabolic cage,which was used for detecting 24 hours’albumin and urine creatinine by kit. Rats were killed and serum was obtained from abdominal aorta, which was used to detect serum creatinine and serum glucose. Cut the kindey,cleaned the kindey amicula then douched the kindey by cool normal saline.The size、colour、texture and the weight of kindey were observed.The tablet renal cortex tissue was cut quickly and fixed with 4% glutaral to observe the fine structure by scanning electron microscope. Part of renal cortex tissue were fixed with 4% paraformaldehyde to make paraffin section for analyzing the protein expression of p38MAPK、nephrin and adiponectin by immunohistochemistry. Part of kindey was cut and freezed by liquid nitrogen to prepare total RNA and protein extracted by tissue bomogenate. RT-PCR and Western blotting were used to evaluate the mRNA and protein expression of p38MAPK、nephrin and adiponectin. The results were analyzed by Quantity One software.All data were dealt with SPSS11.0 statistical software.
Results: 1. The expression of p38MAPK mRNA and protein in selenite-treated group decreased in compared with diabetic nephropathy group,but enhanced in compared with control group. 2.The expression of Nephrin mRNA and protein in selenite-treated group was more than diabetic nephropathy group,but less than control group. 3.The expression of adiponectin mRNA and protein in selenite-treated group markedly enhanced in compared with control group and was more than diabetic nephropathy group, the same as diabetic nephropathy group compared with control group .
Conclusion: Selenite can increase the expression of adiponectin and nephrin, and decrease the expression of p38MAPK by suppressing oxidative stress and enhancing sensitivity to insulin, Which may be related to improve diabetic nephropathy of the rats.
硒是机体必需的微量元素之一,是谷胱甘肽过氧化物酶必需的结构成分,谷胱甘肽过氧化物酶的主要功能是清除体内过氧化物,维持膜系统的完整性。近年来研究发现硒具有降低血糖和调控胰岛素介导的代谢过程等拟胰岛素作用。对糖尿病鼠补充硒不仅可预防氧化应激,而且也可防止肾脏损伤,同时能改善葡萄糖内环境和增强外周组织对胰岛素的敏感性。但硒在防治糖尿病肾病中的作用及机制,国内外报道甚少,所以其在糖尿病肾病中的防治效果和相关分子机制值得进一步探讨。
第一部分亚硒酸钠对糖尿病肾病大鼠基本状况和肾脏病变的干预作用
目的:通过链尿佐菌素法及长期高脂饮食诱导构建糖尿病肾病模型,并长期给予亚硒酸钠口服治疗,探讨硒对糖尿病肾病大鼠基本状况的改善和肾脏病变的延缓作用,评价硒防治糖尿病肾病的效果。
方法:以链尿佐菌素55mg/kg体重剂量一次性腹腔注射及长期高脂饮食喂养构建糖尿病肾病模型,试验设空白组(N)、糖尿病对照组(DM)和亚硒酸钠干预组(DM-Se),干预组给予亚硒酸钠治疗。各组大鼠分笼喂养,实验期间自由进食、进水,自然照明,室温20℃-28℃,均不给与胰岛素和降糖药。喂养10周后,观察各组大鼠全身基本状况。用代谢笼准确收集24小时尿量,用试剂盒检测尿24小时白蛋白和尿肌酐。处死大鼠,腹主动脉取血清,测定血肌酐、血糖等指标。取双肾,去除肾包膜,用冷生理盐水灌洗,同时观察肾脏大小、颜色、质地,称双肾重量。快速切取小块肾皮质组织,4%戊二醛固定,制电镜切片扫描电镜观察超微结构。切取肾脏组织,4%多聚甲醛固定,制石蜡切片HE染色光镜下观察病理改变。所有数据用SPSS11.0软件包分析统计学意义。
结果:
1.药物干预组大鼠较模型对照组全身基本状况明显改善,血糖、肾重/体重比值无明显变化,而血肌酐、尿24小时白蛋白等指标明显改善。
2.干预组大鼠肾脏光镜下组织形态病理变化和电镜下超微结构均较模型对照组明显改善。
结论:
1.亚硒酸钠能显著改善糖尿病肾病大鼠的全身状况。
2.亚硒酸钠能延缓糖尿病肾病大鼠的肾脏病变。
第二部分亚硒酸钠对糖尿病肾病大鼠肾脏p38MAPK、nephrin、adiponectin表达的影响
目的:通过链尿佐菌素法及长期高脂饮食诱导构建糖尿病肾病模型,并长期给予亚硒酸钠口服治疗,探讨硒对糖尿病肾病大鼠肾脏p38MAPK、nephrin、adiponectin表达的影响,从而研究硒在防治糖尿病肾病中的作用机制。
方法:以链尿佐菌素55mg/kg体重剂量一次性腹腔注射及长期给予高脂饮食喂养构建糖尿病肾病模型,试验设空白组(N)、糖尿病对照组(DM)和亚硒酸钠干预组(DM-Se),干预组给予亚硒酸钠治疗。各组大鼠分笼喂养,实验期间自由进食、进水,自然照明,室温20℃-28℃,均不给与胰岛素和降糖药。喂养10周后,处死大鼠,取双肾,去除肾包膜,用冷生理盐水灌洗,同时观察肾脏大小、颜色、质地,称双肾重量。切取肾脏组织,4%多聚甲醛固定,制石蜡切片免疫组化分析p38MAPK、nephrin、adiponectin蛋白表达。切取双肾组织投入液氮冻存,组织匀浆提取总RNA和总蛋白分别用PCR法和Western blotting法分析p38MAPK、nephrin、adiponectin mRNA表达和蛋白表达。相关软件分析图片,获得数据。所有数据用SPSS11.0软件包分析统计学意义。
结果:
1、干预组p38 MAPK mRNA及蛋白表达均较模型对照组降低,但较空白组高。
2、干预组nephrin mRNA及蛋白表达均较模型对照组增加,但较空白组低。
3、干预组adiponectin mRNA及蛋白表达量均较空白组明显增加,较模型对照组增加;模型对照组adiponectin mRNA及蛋白的表达量均较空白组增加。
结论:亚硒酸钠能促进脂联素、nephrin表达,抑制P38MAPK表达,可能与其抑制氧化应激、增加外周组织对胰岛素敏感性,从而改善糖尿病肾脏病变有关。
Background: With the raising of people’s life level and the changing of people’s life style, the rate of diabetic vascular complications is ascending year by year. Diabetic nephropathy is one of the diabetic microvascular complications, and it’s incidence rate is rising in recent years, and it has become the prime cause of End Stage Renal Disease (ESRD). It is one of the serious complications and main death cause of Diabetes mellitus(DM) too. Once emerging persistent proteinuria, the disease should not be reverted, which would develop end stage renal disease eventually. The patients survive only depend on dialysis and vicariousness treatment. So it is important to interfere in earlier period of the disease for delaying the disease process.
Selenium is one of the essential trace element of organism, and it consists in glutathione peroxidase.It’s main function is cleaning organism endoperoxide and keeping up the integrity of membrane system.It is discovered that selenite can imitate insulin to decrease serum glucose and regulate metabolic process mediated by insulin. To supplement selenium for diabetic rats not only protect oxidative stress , but also prevent kindey injury. Simultaneously, it can improve glucose internal environment and the sensitivity of periphery tissue toward insulin. In diabetic nephropathy, selenium intervention effect and molecule mechanism is less reported in internal and overseas, so it is really worth studying.
PART ONE THE EFFECT OF SELENITE ON BASIC CONDITIONS AND PATHOLOGICAL CHANGES OF DIABETIC NEPHROPATHY RATS
Objective: Diabetic nephropathy rat models were established by injecting streptozocin intraperitoneally and feeded high fat diet longly and were treated by oral medication selenite longly.The study would investigate the influence of sodium selenite on basic conditions and pathological changes in kidney of diabetic nephropathy rats, so as to estimate the effect of sodium selenite preventing diabetic nephropathy.
Methods: Diabetic nephropathy rat models were established by feeded high lipid diet and high consistency sucrose and injected intraperitoneally a single streptozocin (STZ) in a dose of 55 mg/kg for the rats. Three different groups of the rats were employed: control group, diabetic nephropathy group and selenite-treated group. Temperature were kept in a 20°C -28°C range. All rats were fed by separate cages, the food and water were ingested without limitation, natural illumination.All rats were not gave insulin and hypoglycemic agent in the whole process.After 10 weeks, the conditions of rats were observed. 24 hours’urine of the rats was collected by metabolic cage,which was used for detecting 24 hours’albumin and urine creatinine by kit. Rats were killed and serum was obtained from abdominal aorta, which was used to detect serum creatinine and serum glucose. Cut the kindey,cleaned the kindey amicula then douched the kindey by cool normal saline.The size、colour、texture and the weight of kindey were observed.The tablet renal cortex tissue was cut quickly and fixed with 4% glutaral to observe the fine structure by scanning electron microscope. Part of renal cortex tissue were fixed with 4% paraformaldehyde to make paraffin section which stained with HE to show kidney pathological changes by light microscope. All data were dealt with SPSS11.0 statistical software.
Results: 1. The basic conditions of selenite-treated group were significant better than diabetic nephropathy group. Kindey/body weight and Serum glucose had no difference between selenite-treated group and diabetic nephropathy group, but there were great differences for Serum creatinine and 24 hours urinary albumin. 2. The pathological changes by light microscope and fine structure changes by electron microscope in kindey of selenite-treated group were better than diabetic nephropathy group.
Conclusion: 1.Selenite can greatly improve the general body state of diabetic nephropathy rats.
2.Selenite can delay the kindey pathological changes of diabetic nephropathy rats
PART TWO THE INFLUENCE OF SELENITE ON p38MAPK、NEPHRIN、ADIPONECTIN EXPRESSION IN KIDNEY OF DIABETIC NEPHROPATHY RATS
Objective: Diabetic nephropathy rat models were established by injecting streptozocin intraperitoneally and feeded high fat diet longly and were treated by oral medication selenite longly.The study would evaluate the effect of sodium selenite on expression of p38MAPK、nephrin、adiponectin, so as to study its molecule mechanism in DN.
Methods:Diabetic nephropathy rat models were established by feeded high lipid diet and high consistency sucrose and injected intraperitoneally a single streptozocin (STZ) in a dose of 55 mg/kg for the rats. Three different groups of the rats were employed: control group, diabetic nephropathy group and selenite-treated group. Temperature were kept in a 20°C-28°C range. All rats were fed by separate cages, the food and water were ingested without limitation, natural illumination.All rats were not gave insulin and hypoglycemic agent in the whole process.After 10 weeks, the conditions of rats were observed. 24 hours’urine of the rats was collected by metabolic cage,which was used for detecting 24 hours’albumin and urine creatinine by kit. Rats were killed and serum was obtained from abdominal aorta, which was used to detect serum creatinine and serum glucose. Cut the kindey,cleaned the kindey amicula then douched the kindey by cool normal saline.The size、colour、texture and the weight of kindey were observed.The tablet renal cortex tissue was cut quickly and fixed with 4% glutaral to observe the fine structure by scanning electron microscope. Part of renal cortex tissue were fixed with 4% paraformaldehyde to make paraffin section for analyzing the protein expression of p38MAPK、nephrin and adiponectin by immunohistochemistry. Part of kindey was cut and freezed by liquid nitrogen to prepare total RNA and protein extracted by tissue bomogenate. RT-PCR and Western blotting were used to evaluate the mRNA and protein expression of p38MAPK、nephrin and adiponectin. The results were analyzed by Quantity One software.All data were dealt with SPSS11.0 statistical software.
Results: 1. The expression of p38MAPK mRNA and protein in selenite-treated group decreased in compared with diabetic nephropathy group,but enhanced in compared with control group. 2.The expression of Nephrin mRNA and protein in selenite-treated group was more than diabetic nephropathy group,but less than control group. 3.The expression of adiponectin mRNA and protein in selenite-treated group markedly enhanced in compared with control group and was more than diabetic nephropathy group, the same as diabetic nephropathy group compared with control group .
Conclusion: Selenite can increase the expression of adiponectin and nephrin, and decrease the expression of p38MAPK by suppressing oxidative stress and enhancing sensitivity to insulin, Which may be related to improve diabetic nephropathy of the rats.
引文
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[5].Bonnefont-Rousselot D,et al. The role of antioxidant micronutrients in the prevention of diabetic complications[J]. Treat Endocrinol. 2004,3(1):41-52.
[6].Erbayraktar Z,Yilmaz,et al.Effects of selenium supplementation on antioxidant defense and glucose homeostasis in experimental diabetes mellitus[J].Biol Trace Elem Res.2007,118(3):217-26.
[7]. Hwang D,Seo S,et al. Selenium acts as an insulin-like molecule for the down-regulation of diabetic symptoms via endoplasmic reticulum stress and insulin signalling proteins in diabetes-induced non-obese diabetic mice[J]. Biosci. 2007, 32(4):723-35.
[8].Alluru S Reddi,et al.Selenium-deficient diet induces renal oxidative stress and injury via TGF-1 in normal and diabetic rats[J].Kidney International. 2001,(59): 1342-353.
[9].Sakai N, Wada T, Furuichi K, et al. Involvement of extracellular signal regulated kinase and p38 in human diabetic nephropathy[J]. Kidney Dis. 2005, 45(1):54-65.
[10].Cuenda A,Rousseau S.p38 MAP-kinases pathway regulation,function and role in human diseases[J].Biochim Biophys Acta.2007,1773(8):1358-75.
[11].Park JK, Ronkina N, et al. Deletion of MK2 signalling in vivo inhibits small Hsp phosphorylation but not diabetic nephropathy [J]. Nephrol Dial Transplant. 2008 , 23(6):1844-1853.
[12].Weigert C, Brodbeck K, Klopfer K,et al. Angiotensin II induces human TGF-β1 promoter activation: similarity to hyperglycaemia[J].Diabetologia. 2002,45 (6):890-8.
[13].Lam KS, xu A.Adiponectin: protection of the endothelium[J].Curr Diab Rep.2005,5(4):254-9.
[14].Daimon M, Oizumi T, Saitoh T , et a1. Decreased serum levels of adiponectin ale a risk factor for the progression to type 2 diabetes in the Japanes epopulation: the Funagata study[J]. Diabetes Care.2003,26(7):2015-2020.
[15].Okamoto Y,Kihara S,Ouchi N,et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice[J]. Circulation. 2002,106:2767-70.
[16].Helen CL, Jonathan K, Tohru F,et al. Adiponectin concentrations are influenced by renal function and diabetes duration inp ima indians with type 2 diabetes[J]. Clin Endocrinol Metab. 2004,89(8):4010.
[17].Chudek J,Adamczak M,Karkoszka H,et al.Plasma adiponectin concentration before and after successful kidney transplantation[J]. Transplant Proc.2003,35: 2186-89.
[18].Yamauchi T, Nio Y, Maki T,et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J].Nat Med. 2007 ,13(3):332-9.
[19]. Sophie Doublier,Gennaro Salvidio,Enrico Lupia,et al.Nephrin Expression Is Reduced in human diabetic nephropathy [J].diabetes, 2003,52(4):1023-1030.
[20].Chen LP,Zhou QL,Peng WS,et al.Changes of podocyte ultrastructure and expression of podocyte-associated molecules in rats with diabetic nephropathy[J]. Zhong Nan Da xue xue Bao Yi xue Ban. 2007,32(4):620-5.
[21].Benigni A, Gagliardini E,Tomasoni S,et al.Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy[J]. Kidney Int. 2004,5(6):2193-200.
[1].Joachim Bleys, Ana Navas-Acien, Eliseo Guallar.Selenium and Diabetes: More Bad News for Supplements [J]. Annals 2007 ,147(4): 271-272.
[2].Rotruck JT,Pope AL,Ganther HE,et al. Selenium: biochemical role as a component of glutathione peroxidase[J]. Science. 1973,179:588-90.
[3]. Stapleton SR.Selenium: an insulin-mimetic [J]. Cell Mol Life Sci, 2000, 57(13-14): 1874-9.
[4].Gregus Z, Perjesi P, Gyurasics A. Enhancement of selenium excretion in the bile by sulfobromophthalein: dlucidation of the mechanism[J]. Biochem Pharmalcol, 1998,56:1391-1402.
[5]Douillet C, Tabib A, Bost M,et al. A selenium supplement associated or not with vitamin E delays early renal lesion in experimental diabetes in rats[J]. Prooc Soc Exp Biol Med.1996;211:323-331.
[6]Mcneill JH. Insulinlike effects of sodium selenate in streptozocin—induced diabetic rats[J]. Diabetes, 1991,40:11675-78.
[7].Becker DJ,Reul B,Ozcelikay AT,et al.Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogeenic enzymes in diabetic rats [J]. Diabetologia, 1996, 39(1): 3-11.
[8].Zhao C, Wang H, Zhang J, et al. Correlations of trace elements, glucose and body compositions in type 2 diabetics [J]. Wei Sheng Yan Jiu. 2008,37(5):600-605.
[9].Kornhauser C, Garcia-Ramirez JR,Wrobel K.Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patient. [J] Prim Care Diabetes. 2008 ,2(2):81-5.
[10].Erbayraktar Z, Yilmaz O, Artmann AT. Effects of selenium supplementation on antioxidant defense and glucose homeostasis in experimental diabetes mellitus[J]. Biol Trace Elem Res. 2007,118(3):217-26.
[11]. Zeng J, Zhou J, Huang K.Effect of selenium on pancreatic proinflammatory cytokines in streptozotocin-induced diabetic mice[J].Nutr Biochem. 2008 Sep 10.
[12].Kiersztan A,Lukasinska I,Baranska A.Differential effects of selenium compounds on glucose synthesis in rabbit kidney-cortex tubules and hepatocytes.In vitro and in vivo studies[J].Inorg Biochem.2007,101(3):493-505.
[13].Mueller AS, Bosse AC, Most E.Regulation of the insulin antagonistic proteintyrosine phosphatase 1B by dietary Se studied in growing rats[J].Nutr Biochem. 2009 ,20(4):235-47.
[14].Mueller AS, Pallauf J.Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice[J]. Nutr Biochem.2006 ,17(8):548-60.
[1].Han J,Lee JD,Bibbs L,et al.A MAP kinase targeted by endotoxin and Hyperomolarity in mammalian cells[J].Science,1994,265:808-811.
[2].Kumar S,McDonnell PC,Rebecca J,et al.Novel homologues of CSBP/p38 MAP kinase:activation,substrate specificity and sensitivity to inhibition by pyridinyl imidazoles[J].Biochem Biophys Res Commun,1997,235:533-8.
[3].Li Z,Jiang Y,Ulevitch RJ,et al.The primary structure of p38 gamma:a new member of p38 group of MAP kinases[J]. Biochem Biophy Res Commun,1996,228:334-340.
[4].Jiang Y,Gram H,Zhao M,et al.Characterization of the structure and function of the fourth member of P38 group mitogen-activated protein kinases, P38 delta [J].Biol Chem,1997,278:30122-30128.
[5].Gruden G,Zonca S,Hayward A,et al.Mechanical stretch-induced fibronectin and transforming growth factor-betal production in human mesangial cells is p38 mitogen-activated protein kinase-dependent[J].Diabetes,2000,49:655-61.
[6].Weigert C,Brodbeck K,Klopfer K,et al.Angiotensin II induces human TGF-β1 promoter activation:similarity to hyperglycaemia[J].Diabetologia,2002,45(6):890-8.
[7].Takahashi M,Arita Y,Yamagata K,et al.Genomic structure and mutations in adipose specific gene,adiponectin[J].Int J Obse,2000,24(7):861-8.
[8].Lam KS,xu A.Adiponectin:protection of the endothelium[J].Curr Diab Rep.2005, 5(4):254-9.
[9].Miyazaki Y,Cersosimo E,Triplitt C, et al.Rosiglitazone decreases albuminuria in type 2 diabetic patients[J].Kidney international,2007,72(11):1367-73.
[10].Daimon M,Oizumi T,Saitoh T,et al.Decreased serum levels of adiponectin ale a risk factor for the progression to type 2 diabetes in the Japanese population:the Funagata study[J].Diabetes Care,2003,26(7):2015-2020.
[11].Okamoto Y,Kihara S,Ouchi N,et al.Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice[J].Circulation,2002,106:2767-2770.
[12].Helen CL,Jonathan K,Tohru F,et al. Adiponectin concentrations are influenced by renal function and diabetes duration inp ima indians with type 2 diabetes[J].Clin Endocrinol Metab.2004,89(8):4010.
[13].Fujita H, Morii T,Koshimura J,et al. Possible relationship between adiponectinand renal tubular injury in diabetic nephropathy[J].Endocrine journal, 2006, 53(6): 745-52.
[14].Kato K, Osawa H, Ochi M,et al. Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy[J].Clin Endocrinol.2008,68(3):442-9.
[15].Sharma K,Ramachandrarao S,Qiu G,et al.Adiponectin regulates albuminuria and podocyte function in mice[J].Clin Invest.2008,118(5):1645-56.
[16].Chudek J,Adamczak M,Karkoszka H,et al.Plasma adiponectin concentration before and after successful kidney transplantation[J].TransplantProc, 2003,35: 2186 -2189.
[17].Yamauchi T, Nio Y, Maki T,et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J].Nat Med. 2007, 13(3):332-9.
[18].Gerth VE, Zhou x, Vize PD.Nephrin expression and three-dimensional morphogenesis of the xenopus pronephric glomus[J].Dev Dyn.2005,233(3):1131-9.
[19].Kim JJ, Li JJ, Jung DS. Differential expression of nephrin according to glomerular size in early diabetic kidney disease[J].Am Soc Nephrol. 2007, 18(8):2303-10.
[20].Chen LP, Zhou QL, Peng WS. Changes of podocyte ultrastructure and expression of podocyte-associated molecules in rats with diabetic nephropathy[J]. Zhong Nan Da xue xue Bao Yi xue Ban. 2007,32(4):620-5.
[21]. Benigni A, Gagliardini E, Tomasoni S. Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy[J].Kidney Int.2004 , 65(6): 2193-200.
[22].Catanuto P,Doublier S,Lupia E.17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes [J].Kidney Int.2009 Mar 11.
[23]. Zhang Z, Zhang Y, Ning G. Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: blockade of compensatory renin increase[J]. Proc Natl Acad Sci USA. 2008 ,105(41):15896-901.
[24].Turk T, Leeuwis JW, Gray J. BMP Signaling and Podocyte Markers Are Decreased in Human Diabetic Nephropathy in Association With CTGF Overexpression [J]. Histochem Cytochem. 2009 Mar 2.
[25].Wu Y, Dong J, Yuan. Nephrin and podocin loss is prevented by mycophenolate mofetil in early experimental diabetic nephropathy [J]. Cytokine. 2008, 44(1):85-91.
[26].Menne J, Meier M, Park JK.Nephrin loss in experimental diabetic nephropathy is prevented by deletion of protein kinase C alpha signaling in-vivo [J]. Kidney Int. 2006,70(8):1456-62.
[27].Cohen MP, Chen S, Ziyadeh FN. Evidence linking glycated albumin to altered glomerular nephrin and VEGF expression, proteinuria, and diabetic nephropathy[J].Kidney Int. 2005 ,68(4):1554-61.
[28].Gopee NV, Johnson VJ, Sharma RP. Sodium selenite-induced apoptosis in murine B-lymphoma cells is associated with inhibition of protein kinase C-delta, nuclear factor kappaB, and inhibitor of apoptosis protein[J]. Toxicol Sci. 2004 ,78(2):204-14.
[1]. Takahashi M,Arita Y, Yamagata K,et al .Genomic structure and mutations in adipose specific gene,adiponectin[J].Int J Obse ,2000,24(7):861-868.
[2].Helen C,Jonathan K,Tohru F,et al.Adiponectin concentrations are influenced by renal function and diabetes duration inp ima indians with type 2 diabetes[J].Clin Endocrinol Metab. 2004, 89(8) : 4010.
[3] .Jun Koshimura, Hiroki Fujita, Takuma Narita, et al. Urinary adiponectin excretion is increased in patients with overt diabetic nephropa2thy[J]. Biochem and Biophys Res Commun. 2004, 316: 165.
[4].Matsumoto S,Takebayashi K, Aso Y.The effect of spironolactone on circulating adipocytokines in patients with type 2 diabetes mellitus complicated by diabetic nephropathy[J].Metabolism: clinical and experimental, 2006,55(12):1645-52.
[5].Kato K, Osawa H, Ochi M, et al. Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy andnephropathy[J].Clin Endocrinology, 2008 68(3):442-9.
[6].Williams KJ,Qiu G,Usui HK,et al.Decorin deficiency enhances progressive nephro- pathy in diabetic mice[J].The American journal of pathology, 2007,171(5):1441-50.
[7].Kollerits B, Fliser D, Heid IM, et al. Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the Mild to Moderate Kidney Disease Study[J]. Kidney international, 2007,71(12):1279-86.
[8].Shimotomai T, Kakei M, Narita T, et al. Enhanced urinary adiponectin excretion in IgA-nephropathy patients with proteinuria[J]. Renal failure, 2005,27(3):323-8.
[9].Komaba H, Igaki N, Goto S, et al. Increased serum high-molecular-weight complex of adiponectin in type 2 diabetic patients with impaired renal function[J].American journal of nephrology, 2006,26(5):476-82.
[10] .Fujita H, Morii T, Koshimura J, et al. Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy[J].Endocrine journal, 2006,53(6):745-52.
[11] Freedman BI, Bostrom M, Daeihagh P,et al. Genetic factors in diabetic nephropathy [J].Clinical journal of the American Society of Nephrology. 2007,2(6):1306-16.
[12].Vionnet N, Tregouet D, Kazeem G, et al. Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene[J]. Diabetes, 2006,55(11):3166-74.
[13].Rudofsky G Jr, Schlimme M, Schlotterer A, et al. No association of the 94T/G polymorphism in the adiponectin gene with diabetic complications[J]. Diabetes, obesity & metabolism, 2005,7(4):455-9.
[14].Yoshioka K, Yoshida T, Umekawa T, et al. Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients[J]. Metabolism: clinical and experimental, 2004,53(9):1223-6.
[15].Menzaghi C,Trischitta V,et al. Genetic influences of adiponectin on insulin resistance,type 2 diabetes, and cardiovascular disease[J].Diabetes 2007 565 1198-209.
[16] .Miyazaki Y, Cersosimo E, Triplitt C, et al. Rosiglitazone decreases albuminuria in type 2 diabetic patients[J]. Kidney international, 2007,72(11):1367-73.
[17].Matsuda M, Kawasaki F, Yamada K, et al. Impact of adiposity and plasma adipocytokines on diabetic angiopathies in Japanese Type 2 diabetic subjects[J]. Diabetic medicine.2004,21(8):881-8.
[18].Yilmaz MI, Saglam M, Qureshi AR, et al. Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin[J]. Nephrol Dial Transplant, 2008.
[19].Kobayashi S, Satoh M, Namikoshi T, et al. Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy[J]. Clin Exp Nephrol, 2008.
[20] .Malyszko J, Malyszko JS, Brzosko S, et al. Adiponectin is related to CD146, a novel marker of endothelial cell activation/injury in chronic renal failure and peritoneally dialyzed patients[J]. The Journal of clinical endocrinology and metabolism, 2004,89(9):4620-7.
[21].Lam KS;xu A,et,al. Adiponectin: protection of the endothelium[J]. Current diabetes reports .2005,5(4):254-9
[22] .Cha DR, Zhang x, Zhang Y, et al.Peroxisome proliferator activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice[J]. Diabetes, 2007,56(8):2036-45.
[23] .Yamauchi T, Kamom J , Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects[J]. Nature, 2003, 423: 762～769.
[24].Yamauchi T et.al Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J]. Nat Med. 2007 ,13(3):332-9.
[25] .Misra P. AMP activated protein kinase: a next generation target for total metabolic control[J]. Expert Opin Ther Targets. 2008 ,12(1):91-100.
[2].Bai Y,Wang L,Li Y,et al.High ambient glucose levels modulates the production of MMP-9 and alpha5(IV) collagen by cultured podocytes [J]. Cell Physiol Biochem. 2006,17(1-2):57-68.
[3].Forbes JM,Fukami K,Cooper ME.Diabetic nephropathy:where hemodynamics meets metabolism [J]. Exp Clin Endocrinol Diabetes.2007,115(2): 69-84.
[4].Beckett GJ, Arthur JR., et al.Selenium and endocrine systems[J]. Endocrinol. 2005 ,184(3):455-65.
[5].Bonnefont-Rousselot D,et al. The role of antioxidant micronutrients in the prevention of diabetic complications[J]. Treat Endocrinol. 2004,3(1):41-52.
[6].Erbayraktar Z,Yilmaz,et al.Effects of selenium supplementation on antioxidant defense and glucose homeostasis in experimental diabetes mellitus[J].Biol Trace Elem Res.2007,118(3):217-26.
[7]. Hwang D,Seo S,et al. Selenium acts as an insulin-like molecule for the down-regulation of diabetic symptoms via endoplasmic reticulum stress and insulin signalling proteins in diabetes-induced non-obese diabetic mice[J]. Biosci. 2007, 32(4):723-35.
[8].Alluru S Reddi,et al.Selenium-deficient diet induces renal oxidative stress and injury via TGF-1 in normal and diabetic rats[J].Kidney International. 2001,(59): 1342-353.
[9].Sakai N, Wada T, Furuichi K, et al. Involvement of extracellular signal regulated kinase and p38 in human diabetic nephropathy[J]. Kidney Dis. 2005, 45(1):54-65.
[10].Cuenda A,Rousseau S.p38 MAP-kinases pathway regulation,function and role in human diseases[J].Biochim Biophys Acta.2007,1773(8):1358-75.
[11].Park JK, Ronkina N, et al. Deletion of MK2 signalling in vivo inhibits small Hsp phosphorylation but not diabetic nephropathy [J]. Nephrol Dial Transplant. 2008 , 23(6):1844-1853.
[12].Weigert C, Brodbeck K, Klopfer K,et al. Angiotensin II induces human TGF-β1 promoter activation: similarity to hyperglycaemia[J].Diabetologia. 2002,45 (6):890-8.
[13].Lam KS, xu A.Adiponectin: protection of the endothelium[J].Curr Diab Rep.2005,5(4):254-9.
[14].Daimon M, Oizumi T, Saitoh T , et a1. Decreased serum levels of adiponectin ale a risk factor for the progression to type 2 diabetes in the Japanes epopulation: the Funagata study[J]. Diabetes Care.2003,26(7):2015-2020.
[15].Okamoto Y,Kihara S,Ouchi N,et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice[J]. Circulation. 2002,106:2767-70.
[16].Helen CL, Jonathan K, Tohru F,et al. Adiponectin concentrations are influenced by renal function and diabetes duration inp ima indians with type 2 diabetes[J]. Clin Endocrinol Metab. 2004,89(8):4010.
[17].Chudek J,Adamczak M,Karkoszka H,et al.Plasma adiponectin concentration before and after successful kidney transplantation[J]. Transplant Proc.2003,35: 2186-89.
[18].Yamauchi T, Nio Y, Maki T,et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J].Nat Med. 2007 ,13(3):332-9.
[19]. Sophie Doublier,Gennaro Salvidio,Enrico Lupia,et al.Nephrin Expression Is Reduced in human diabetic nephropathy [J].diabetes, 2003,52(4):1023-1030.
[20].Chen LP,Zhou QL,Peng WS,et al.Changes of podocyte ultrastructure and expression of podocyte-associated molecules in rats with diabetic nephropathy[J]. Zhong Nan Da xue xue Bao Yi xue Ban. 2007,32(4):620-5.
[21].Benigni A, Gagliardini E,Tomasoni S,et al.Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy[J]. Kidney Int. 2004,5(6):2193-200.
[1].Joachim Bleys, Ana Navas-Acien, Eliseo Guallar.Selenium and Diabetes: More Bad News for Supplements [J]. Annals 2007 ,147(4): 271-272.
[2].Rotruck JT,Pope AL,Ganther HE,et al. Selenium: biochemical role as a component of glutathione peroxidase[J]. Science. 1973,179:588-90.
[3]. Stapleton SR.Selenium: an insulin-mimetic [J]. Cell Mol Life Sci, 2000, 57(13-14): 1874-9.
[4].Gregus Z, Perjesi P, Gyurasics A. Enhancement of selenium excretion in the bile by sulfobromophthalein: dlucidation of the mechanism[J]. Biochem Pharmalcol, 1998,56:1391-1402.
[5]Douillet C, Tabib A, Bost M,et al. A selenium supplement associated or not with vitamin E delays early renal lesion in experimental diabetes in rats[J]. Prooc Soc Exp Biol Med.1996;211:323-331.
[6]Mcneill JH. Insulinlike effects of sodium selenate in streptozocin—induced diabetic rats[J]. Diabetes, 1991,40:11675-78.
[7].Becker DJ,Reul B,Ozcelikay AT,et al.Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogeenic enzymes in diabetic rats [J]. Diabetologia, 1996, 39(1): 3-11.
[8].Zhao C, Wang H, Zhang J, et al. Correlations of trace elements, glucose and body compositions in type 2 diabetics [J]. Wei Sheng Yan Jiu. 2008,37(5):600-605.
[9].Kornhauser C, Garcia-Ramirez JR,Wrobel K.Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patient. [J] Prim Care Diabetes. 2008 ,2(2):81-5.
[10].Erbayraktar Z, Yilmaz O, Artmann AT. Effects of selenium supplementation on antioxidant defense and glucose homeostasis in experimental diabetes mellitus[J]. Biol Trace Elem Res. 2007,118(3):217-26.
[11]. Zeng J, Zhou J, Huang K.Effect of selenium on pancreatic proinflammatory cytokines in streptozotocin-induced diabetic mice[J].Nutr Biochem. 2008 Sep 10.
[12].Kiersztan A,Lukasinska I,Baranska A.Differential effects of selenium compounds on glucose synthesis in rabbit kidney-cortex tubules and hepatocytes.In vitro and in vivo studies[J].Inorg Biochem.2007,101(3):493-505.
[13].Mueller AS, Bosse AC, Most E.Regulation of the insulin antagonistic proteintyrosine phosphatase 1B by dietary Se studied in growing rats[J].Nutr Biochem. 2009 ,20(4):235-47.
[14].Mueller AS, Pallauf J.Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice[J]. Nutr Biochem.2006 ,17(8):548-60.
[1].Han J,Lee JD,Bibbs L,et al.A MAP kinase targeted by endotoxin and Hyperomolarity in mammalian cells[J].Science,1994,265:808-811.
[2].Kumar S,McDonnell PC,Rebecca J,et al.Novel homologues of CSBP/p38 MAP kinase:activation,substrate specificity and sensitivity to inhibition by pyridinyl imidazoles[J].Biochem Biophys Res Commun,1997,235:533-8.
[3].Li Z,Jiang Y,Ulevitch RJ,et al.The primary structure of p38 gamma:a new member of p38 group of MAP kinases[J]. Biochem Biophy Res Commun,1996,228:334-340.
[4].Jiang Y,Gram H,Zhao M,et al.Characterization of the structure and function of the fourth member of P38 group mitogen-activated protein kinases, P38 delta [J].Biol Chem,1997,278:30122-30128.
[5].Gruden G,Zonca S,Hayward A,et al.Mechanical stretch-induced fibronectin and transforming growth factor-betal production in human mesangial cells is p38 mitogen-activated protein kinase-dependent[J].Diabetes,2000,49:655-61.
[6].Weigert C,Brodbeck K,Klopfer K,et al.Angiotensin II induces human TGF-β1 promoter activation:similarity to hyperglycaemia[J].Diabetologia,2002,45(6):890-8.
[7].Takahashi M,Arita Y,Yamagata K,et al.Genomic structure and mutations in adipose specific gene,adiponectin[J].Int J Obse,2000,24(7):861-8.
[8].Lam KS,xu A.Adiponectin:protection of the endothelium[J].Curr Diab Rep.2005, 5(4):254-9.
[9].Miyazaki Y,Cersosimo E,Triplitt C, et al.Rosiglitazone decreases albuminuria in type 2 diabetic patients[J].Kidney international,2007,72(11):1367-73.
[10].Daimon M,Oizumi T,Saitoh T,et al.Decreased serum levels of adiponectin ale a risk factor for the progression to type 2 diabetes in the Japanese population:the Funagata study[J].Diabetes Care,2003,26(7):2015-2020.
[11].Okamoto Y,Kihara S,Ouchi N,et al.Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice[J].Circulation,2002,106:2767-2770.
[12].Helen CL,Jonathan K,Tohru F,et al. Adiponectin concentrations are influenced by renal function and diabetes duration inp ima indians with type 2 diabetes[J].Clin Endocrinol Metab.2004,89(8):4010.
[13].Fujita H, Morii T,Koshimura J,et al. Possible relationship between adiponectinand renal tubular injury in diabetic nephropathy[J].Endocrine journal, 2006, 53(6): 745-52.
[14].Kato K, Osawa H, Ochi M,et al. Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy[J].Clin Endocrinol.2008,68(3):442-9.
[15].Sharma K,Ramachandrarao S,Qiu G,et al.Adiponectin regulates albuminuria and podocyte function in mice[J].Clin Invest.2008,118(5):1645-56.
[16].Chudek J,Adamczak M,Karkoszka H,et al.Plasma adiponectin concentration before and after successful kidney transplantation[J].TransplantProc, 2003,35: 2186 -2189.
[17].Yamauchi T, Nio Y, Maki T,et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J].Nat Med. 2007, 13(3):332-9.
[18].Gerth VE, Zhou x, Vize PD.Nephrin expression and three-dimensional morphogenesis of the xenopus pronephric glomus[J].Dev Dyn.2005,233(3):1131-9.
[19].Kim JJ, Li JJ, Jung DS. Differential expression of nephrin according to glomerular size in early diabetic kidney disease[J].Am Soc Nephrol. 2007, 18(8):2303-10.
[20].Chen LP, Zhou QL, Peng WS. Changes of podocyte ultrastructure and expression of podocyte-associated molecules in rats with diabetic nephropathy[J]. Zhong Nan Da xue xue Bao Yi xue Ban. 2007,32(4):620-5.
[21]. Benigni A, Gagliardini E, Tomasoni S. Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy[J].Kidney Int.2004 , 65(6): 2193-200.
[22].Catanuto P,Doublier S,Lupia E.17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes [J].Kidney Int.2009 Mar 11.
[23]. Zhang Z, Zhang Y, Ning G. Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: blockade of compensatory renin increase[J]. Proc Natl Acad Sci USA. 2008 ,105(41):15896-901.
[24].Turk T, Leeuwis JW, Gray J. BMP Signaling and Podocyte Markers Are Decreased in Human Diabetic Nephropathy in Association With CTGF Overexpression [J]. Histochem Cytochem. 2009 Mar 2.
[25].Wu Y, Dong J, Yuan. Nephrin and podocin loss is prevented by mycophenolate mofetil in early experimental diabetic nephropathy [J]. Cytokine. 2008, 44(1):85-91.
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