高尿酸血症合并高脂高糖大鼠模型中医证候特点的实验研究
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摘要
目的：
为了探讨高尿酸血症动物模型的中医病理及证候特点,采用腺嘌呤灌胃和高脂高糖饲料喂饲的方法复制高尿酸血症大鼠模型,分别以不同中医治法方药——四妙散、二陈汤、血府逐瘀汤、四君子汤、肾气丸进行反证,进而为高尿酸血症的中西医结合防治和药物开发提供基础研究。
方法：
将56只清洁级成年SD大鼠按体质量(体重200-230g)随机分为7组,即正常组、模型组、四妙散组、二陈汤组、血府逐瘀汤组、四君子汤组、肾气丸组。正常组给予正常饮食,其余各组均以高脂高糖饲料喂养5周。喂养3周后,模型组及各药物治疗组上午固定时间以腺嘌呤200mg/kg灌胃,正常组给予等量蒸馏水灌胃；各药物组下午固定时间分别按组别给予5种方药,模型组和正常组给予等量蒸馏水灌胃,连续2周。所有动物给药体积均为10ml/kg。末次给药后1h,动物称重后腹腔注射戊巴比妥钠(45mg/kg)麻醉,腹主动脉采血,检测血清尿酸(UA)、甘油三酯(TG)、高密度脂蛋白(HDL)、胰岛素(INS)、血糖(GLU)、肌酐(Cr)、尿素氮(BUN)含量；光镜下观察大鼠肾组织病理形态变化；测定肝脏XOD含量及采用逆转录—聚合酶链反应(RT-PCR)法检测XOD-mRNA变化。
结果：
(1)模型组较正常组UA、BUN、Cr、TG、GLU、HDL、肝脏XOD均有显著升高(P<0.05),模型组较正常组INS显著降低(P<0.05),①各药物组UA与模型组比较显著降低(P<0.05),四妙散组与血府逐瘀汤组、二陈汤组之间无明显差异,且这3组疗效好于肾气丸组与四君子汤组,肾气丸组与四君子汤组之间无明显差异；②四妙散组与模型组BUN比较显著降低(P<0.05)；③四妙散、二陈汤、四君子汤组、肾气丸组与模型组Cr比较均显著降低(P<0.05),四妙散组、二陈汤组、肾气丸组之间无明显差异；④各药物组TG与模型组比较均显著降低(P<0.05),各药物组之间比较无明显差异；⑤四妙散组、二陈汤组、血府逐瘀汤组、四君子汤组与模型组GLU比较均显著降低(P<0.05),这4组之间无明显差异；⑥各药物组与模型组HDL比较均无明显差异；⑦四妙散组及血府逐瘀汤组与模型组INS比较显著升高(P<0.05),这2组之间无明显差异；⑧四妙散组、二陈汤组、血府逐瘀汤组、四君子汤组与模型组肝XOD比较显著降低(P<0.05),四妙散组、二陈汤组、四君子汤组之间无明显差异。
(2)光镜观察四妙散、血府逐瘀汤、肾气丸均能不同程度改善大鼠肾组织受损情况,但是四妙散组肾脏结构比较完整,细胞排列比较规则,尿酸盐减少,说明四妙散可以减少尿酸盐的生成,对肾脏起到了较强的保护作用。
(3)肝组织XOD-mRNA表达显示模型组与正常组之间有显著性差异(P<0.05),各药物组与模型组均有显著性差异(P<0.05),四妙散组、二陈汤组、血府逐瘀汤组无明显差异,且3组XOD-mRNA表达均低于四君子汤组及肾气丸组,四君子汤组与肾气丸组无明显差异。
结论：
1.采用腺嘌呤200mg/kg灌胃同时予高脂高糖饮食可以成功制备高尿酸血症、高脂高糖复合大鼠模型。
2.①四妙散可以降低血清UA、TG、GLU、BUN、Cr含量,抑制肝脏XOD活性、抑制XOD-mRNA表达,升高INS含量；②二陈汤可以降低血清UA、TG、GLU、Cr含量,抑制肝脏XOD活性、抑制XOD-mRNA表达；③血府逐瘀汤可以降低血清UA、TG、GLU含量,抑制XOD-mRNA表达,升高INS含量；④四君子汤可以降低血清UA、TG、GLU、Cr含量,抑制肝脏XOD活性、抑制XOD-mRNA表达；⑤肾气丸可以降低血清UA、TG、Cr含量,抑制XOD-mRNA表达。
3.此种方法复制出的高尿酸血症动物模型存在不同程度的肾虚、脾虚、湿热、痰浊、瘀血等病理变化,而四妙散在8个指标中显示出突出的治疗作用,在改善肾功能、抑制肝脏XOD活性、保护肾组织等方面作用最为显著,说明“湿热”可能是该模型的主要病理特点。
Objective:
To explore the pathological features and the characteristics of TCM syndrome in rat model of hyperuricemia,the adenine was lavaged and high fat and high sugar food was fed to copy the rat model of hyperuricemia,and using different prescriptions Simiaosan,Erchentang,Xuefuzhuyu-tang,Sijunzitang,Shenqiwan in the treatment methods to reverse.To provide basic research for prevention/treatment and drug development of Chinese and Western medicine.
Methods:
56adult Clean-level SD rats (weight 200-230g) were randomly divided into seven groups.They were normal control group,model control group,simiaosan treatment group,Erchentang treatment group,Xuefuzhuyutang treatment group,Sijunzitang treatment group and Shenqiwan treatment group.The normal control group was given normal diet, and the other groups were fed high-fat and high-sugar diets for five weeks.After feeding three weeks,the model control group and the drug treatment groups were fed adenine 200mg/kg by a fixed time in the morning,but the normal control group was fed with equal distilled water.In the afternoon, the drug treatment groups were respectively fed with the five kinds of prescriptions,the model control group and the normal control group were fed with equal distilled water by a fixed time.All animals were administered volume 10ml/kg.After 1 hour of the last administration,animals were taken their quality and anesthetized by sodium pentobarbital(45mg/kg) by intraperitoneal.Then took the abdominal aortic blood for detecting the levels of the serum uric acid(UA),triglycerides(TG),high-density lipoprotein(HDL),insulin(INS),glucose(GLU),creatinine(Cr),blood urea nitrogen(BUN).The pathological changes of kidney tissues were observed by light microscopy.The liver homogenate was used to detect the concentration of xod,and reverse transcription-polymerase chain reaction (RT-PCR) was used to detect changes in XOD-mRNA.
Results:
(1)①The levels of HDL,TG,GLU,BUN,Cr,liver XOD were significantly different(P<0.05) between the model group than the normal group.The level of UA was significantly lower(P<0.05) in each drug group than the model group,but there was no significant difference among Simiaosan,Xuefuzhuyutang and Erchentang groups.And this three groups were better than Shenqiwan and Sijunzitang groups.The Shenqiwan group and Sijunzitang group had no significantly difference.②The level of BUN was significantly lower(P<0.05) in Simiaosan than the model group.③The level of Cr was significantly lower(P<0.05) in Simiaosan,Erchentang,Sijunzitang,Shenqiwan groups than in the model group,and there was no significant difference among Simiaosan,Erchentang and Shenqiwan groups.④The level of TG was significantly lower(P<0.05) in each drug group than the model group,and there was no significant difference in drug groups.⑤The level of GLU was significantly lower(P<0.05) in Simiaosan,Erchentang,Xuefuzhuyutang,Sijunzitang group than the model group,and there was no significant difference in this four drug groups.⑥The level of HDL in each drug group had no significant difference with the model group.⑦The level of INS was significantly higher in Simiaosan,Xuefuzhuyutang group than the model group,and there was no significant difference in this two drug groups.⑧The level of liver XOD was significantly lower(P<0.05) in Simiaosan,Erchentang,Sijunzi-tang group than the model group,and there was no significant difference in Simiaosan,Erchentang and Sijunzitang group.
(2) Optical observations indicate that Simiaosan,Xuefuzhuyutang and Shenqiwan can be improved to some extent damage of renal tissue of the rats,but the renal structure of simiaosan group was relatively complete and the arrangement of cells were rules,and the uric acid salt was reduced,so Simiaosan can reduce the formation of urate,plays a strong protective effect in kidney.
(3) The XOD-mRNA expression in liver tissue of model group and normal group showed a significant difference(P<0.05),each drug group and model group were significantly different (P<0.05),Four Simiaosan group,Erchen group and Xuefuzhuyutang group was no significant difference,and the XOD-mRNA expression in the three groups were lower than the Sijunzitang group and Shenqiwan group,Sijunzitang group and Shenqiwan group was no significant difference.
Conclusion:
(1) Using adenine 200mg/kg lavage and high-fat and high-sugar diets can be successful preparation high uric acid,fatty high sugar compound model of rats.
(2)①Simiaosan can reduce the content of serum of UA,TG,GLU,Cr,BUN inhibit the activity of liver XOD and XOD-mRNA expression,elevated the content of serum of INS.②Erchentang can reduce the content of serum of UA,TG,GLU,Cr inhibit the activity of liver XOD and XOD-mRNA expression,elevated the content of serum of INS.③Xuefuzhuyutang can reduce the content of serum of UA,TG,GLU and inhibited the XOD-mRNA expression,elevated the content of serum of INS.④Sijunzitang can reduce the content of serum of UA,TG,GLU,Cr inhibit the activity of liver XOD and XOD-mRNA expression,elevated the content of serum of INS.⑤Shenqiwan can reduce the content of serum of UA,TG,Cr and inhibited the XOD-mRNA expression,elevated the content of serum of INS.
(3) This method to replicate animal model of hyperuricemia varying degrees of kidney,spleen, damp heat,phlegm,blood stasis and other pathological changes.Simiaosan scattered eight indicators of treatment showed prominent role in the improvement of renal function,inhibit the activity of liver XOD.Protect the kidney is the most significant aspects.So the "heat" may be the main pathological features of the model.
为了探讨高尿酸血症动物模型的中医病理及证候特点,采用腺嘌呤灌胃和高脂高糖饲料喂饲的方法复制高尿酸血症大鼠模型,分别以不同中医治法方药——四妙散、二陈汤、血府逐瘀汤、四君子汤、肾气丸进行反证,进而为高尿酸血症的中西医结合防治和药物开发提供基础研究。
方法：
将56只清洁级成年SD大鼠按体质量(体重200-230g)随机分为7组,即正常组、模型组、四妙散组、二陈汤组、血府逐瘀汤组、四君子汤组、肾气丸组。正常组给予正常饮食,其余各组均以高脂高糖饲料喂养5周。喂养3周后,模型组及各药物治疗组上午固定时间以腺嘌呤200mg/kg灌胃,正常组给予等量蒸馏水灌胃；各药物组下午固定时间分别按组别给予5种方药,模型组和正常组给予等量蒸馏水灌胃,连续2周。所有动物给药体积均为10ml/kg。末次给药后1h,动物称重后腹腔注射戊巴比妥钠(45mg/kg)麻醉,腹主动脉采血,检测血清尿酸(UA)、甘油三酯(TG)、高密度脂蛋白(HDL)、胰岛素(INS)、血糖(GLU)、肌酐(Cr)、尿素氮(BUN)含量；光镜下观察大鼠肾组织病理形态变化；测定肝脏XOD含量及采用逆转录—聚合酶链反应(RT-PCR)法检测XOD-mRNA变化。
结果：
(1)模型组较正常组UA、BUN、Cr、TG、GLU、HDL、肝脏XOD均有显著升高(P<0.05),模型组较正常组INS显著降低(P<0.05),①各药物组UA与模型组比较显著降低(P<0.05),四妙散组与血府逐瘀汤组、二陈汤组之间无明显差异,且这3组疗效好于肾气丸组与四君子汤组,肾气丸组与四君子汤组之间无明显差异；②四妙散组与模型组BUN比较显著降低(P<0.05)；③四妙散、二陈汤、四君子汤组、肾气丸组与模型组Cr比较均显著降低(P<0.05),四妙散组、二陈汤组、肾气丸组之间无明显差异；④各药物组TG与模型组比较均显著降低(P<0.05),各药物组之间比较无明显差异；⑤四妙散组、二陈汤组、血府逐瘀汤组、四君子汤组与模型组GLU比较均显著降低(P<0.05),这4组之间无明显差异；⑥各药物组与模型组HDL比较均无明显差异；⑦四妙散组及血府逐瘀汤组与模型组INS比较显著升高(P<0.05),这2组之间无明显差异；⑧四妙散组、二陈汤组、血府逐瘀汤组、四君子汤组与模型组肝XOD比较显著降低(P<0.05),四妙散组、二陈汤组、四君子汤组之间无明显差异。
(2)光镜观察四妙散、血府逐瘀汤、肾气丸均能不同程度改善大鼠肾组织受损情况,但是四妙散组肾脏结构比较完整,细胞排列比较规则,尿酸盐减少,说明四妙散可以减少尿酸盐的生成,对肾脏起到了较强的保护作用。
(3)肝组织XOD-mRNA表达显示模型组与正常组之间有显著性差异(P<0.05),各药物组与模型组均有显著性差异(P<0.05),四妙散组、二陈汤组、血府逐瘀汤组无明显差异,且3组XOD-mRNA表达均低于四君子汤组及肾气丸组,四君子汤组与肾气丸组无明显差异。
结论：
1.采用腺嘌呤200mg/kg灌胃同时予高脂高糖饮食可以成功制备高尿酸血症、高脂高糖复合大鼠模型。
2.①四妙散可以降低血清UA、TG、GLU、BUN、Cr含量,抑制肝脏XOD活性、抑制XOD-mRNA表达,升高INS含量；②二陈汤可以降低血清UA、TG、GLU、Cr含量,抑制肝脏XOD活性、抑制XOD-mRNA表达；③血府逐瘀汤可以降低血清UA、TG、GLU含量,抑制XOD-mRNA表达,升高INS含量；④四君子汤可以降低血清UA、TG、GLU、Cr含量,抑制肝脏XOD活性、抑制XOD-mRNA表达；⑤肾气丸可以降低血清UA、TG、Cr含量,抑制XOD-mRNA表达。
3.此种方法复制出的高尿酸血症动物模型存在不同程度的肾虚、脾虚、湿热、痰浊、瘀血等病理变化,而四妙散在8个指标中显示出突出的治疗作用,在改善肾功能、抑制肝脏XOD活性、保护肾组织等方面作用最为显著,说明“湿热”可能是该模型的主要病理特点。
Objective:
To explore the pathological features and the characteristics of TCM syndrome in rat model of hyperuricemia,the adenine was lavaged and high fat and high sugar food was fed to copy the rat model of hyperuricemia,and using different prescriptions Simiaosan,Erchentang,Xuefuzhuyu-tang,Sijunzitang,Shenqiwan in the treatment methods to reverse.To provide basic research for prevention/treatment and drug development of Chinese and Western medicine.
Methods:
56adult Clean-level SD rats (weight 200-230g) were randomly divided into seven groups.They were normal control group,model control group,simiaosan treatment group,Erchentang treatment group,Xuefuzhuyutang treatment group,Sijunzitang treatment group and Shenqiwan treatment group.The normal control group was given normal diet, and the other groups were fed high-fat and high-sugar diets for five weeks.After feeding three weeks,the model control group and the drug treatment groups were fed adenine 200mg/kg by a fixed time in the morning,but the normal control group was fed with equal distilled water.In the afternoon, the drug treatment groups were respectively fed with the five kinds of prescriptions,the model control group and the normal control group were fed with equal distilled water by a fixed time.All animals were administered volume 10ml/kg.After 1 hour of the last administration,animals were taken their quality and anesthetized by sodium pentobarbital(45mg/kg) by intraperitoneal.Then took the abdominal aortic blood for detecting the levels of the serum uric acid(UA),triglycerides(TG),high-density lipoprotein(HDL),insulin(INS),glucose(GLU),creatinine(Cr),blood urea nitrogen(BUN).The pathological changes of kidney tissues were observed by light microscopy.The liver homogenate was used to detect the concentration of xod,and reverse transcription-polymerase chain reaction (RT-PCR) was used to detect changes in XOD-mRNA.
Results:
(1)①The levels of HDL,TG,GLU,BUN,Cr,liver XOD were significantly different(P<0.05) between the model group than the normal group.The level of UA was significantly lower(P<0.05) in each drug group than the model group,but there was no significant difference among Simiaosan,Xuefuzhuyutang and Erchentang groups.And this three groups were better than Shenqiwan and Sijunzitang groups.The Shenqiwan group and Sijunzitang group had no significantly difference.②The level of BUN was significantly lower(P<0.05) in Simiaosan than the model group.③The level of Cr was significantly lower(P<0.05) in Simiaosan,Erchentang,Sijunzitang,Shenqiwan groups than in the model group,and there was no significant difference among Simiaosan,Erchentang and Shenqiwan groups.④The level of TG was significantly lower(P<0.05) in each drug group than the model group,and there was no significant difference in drug groups.⑤The level of GLU was significantly lower(P<0.05) in Simiaosan,Erchentang,Xuefuzhuyutang,Sijunzitang group than the model group,and there was no significant difference in this four drug groups.⑥The level of HDL in each drug group had no significant difference with the model group.⑦The level of INS was significantly higher in Simiaosan,Xuefuzhuyutang group than the model group,and there was no significant difference in this two drug groups.⑧The level of liver XOD was significantly lower(P<0.05) in Simiaosan,Erchentang,Sijunzi-tang group than the model group,and there was no significant difference in Simiaosan,Erchentang and Sijunzitang group.
(2) Optical observations indicate that Simiaosan,Xuefuzhuyutang and Shenqiwan can be improved to some extent damage of renal tissue of the rats,but the renal structure of simiaosan group was relatively complete and the arrangement of cells were rules,and the uric acid salt was reduced,so Simiaosan can reduce the formation of urate,plays a strong protective effect in kidney.
(3) The XOD-mRNA expression in liver tissue of model group and normal group showed a significant difference(P<0.05),each drug group and model group were significantly different (P<0.05),Four Simiaosan group,Erchen group and Xuefuzhuyutang group was no significant difference,and the XOD-mRNA expression in the three groups were lower than the Sijunzitang group and Shenqiwan group,Sijunzitang group and Shenqiwan group was no significant difference.
Conclusion:
(1) Using adenine 200mg/kg lavage and high-fat and high-sugar diets can be successful preparation high uric acid,fatty high sugar compound model of rats.
(2)①Simiaosan can reduce the content of serum of UA,TG,GLU,Cr,BUN inhibit the activity of liver XOD and XOD-mRNA expression,elevated the content of serum of INS.②Erchentang can reduce the content of serum of UA,TG,GLU,Cr inhibit the activity of liver XOD and XOD-mRNA expression,elevated the content of serum of INS.③Xuefuzhuyutang can reduce the content of serum of UA,TG,GLU and inhibited the XOD-mRNA expression,elevated the content of serum of INS.④Sijunzitang can reduce the content of serum of UA,TG,GLU,Cr inhibit the activity of liver XOD and XOD-mRNA expression,elevated the content of serum of INS.⑤Shenqiwan can reduce the content of serum of UA,TG,Cr and inhibited the XOD-mRNA expression,elevated the content of serum of INS.
(3) This method to replicate animal model of hyperuricemia varying degrees of kidney,spleen, damp heat,phlegm,blood stasis and other pathological changes.Simiaosan scattered eight indicators of treatment showed prominent role in the improvement of renal function,inhibit the activity of liver XOD.Protect the kidney is the most significant aspects.So the "heat" may be the main pathological features of the model.
引文
[1]黄胜光,谭宁,周汝云.除湿化瘀方防治大鼠高尿酸血症的研究[J].中国中医药信息杂志,2004,11(8)：692-694.
[2]郑平东等.用腺嘌呤制作慢性肾功能衰竭动物模型.中华肾脏病杂志,1989,5(6)：342.
[3]王小京,李龙宫.比色法测定腺嘌呤氧化酶.生物化学与生物物理进展,1996,3(5)：65-70.
[4]迟秀梅等.海洛因对C6细胞嘌呤核苷酸分解代谢基因表达的影响.中国实验诊断学,2008,12(5)：589.
[5]阚幕洁等.吗啡对肠道嘌呤核苷酸分解代谢的影响.吉林大学学报,2004,30(2)：2009.
[6]苗志敏.痛风病学.2006,11.
[7]李宁,孙惠新,汪履秋治疗痛风经验撷萃.安徽中医临床杂志,1998,1(1)：32.
[8]张冰,刘小青等.鹌鹑高尿酸血症中医证候学研究.北京中医药大学报,2006,29(10)：676-678.
[9]孙景波,华荣等.用以药测证原理研究慢性肾衰大鼠模型的中医证候属性.现代中医药,2004,(2).
[10]高碧珍,李延平,李灿东等.不同中医治法方药对高尿酸血症大鼠体重及生化指标的影响.中国中医药科技,2008,15(3)：180-181.
[11]高碧珍,李延平,李灿东等.不同方药对高尿酸血症大鼠模型黄嘌呤氧化酶及肾功能的影响.中华中医药杂志,2008,23(2)：97-99.
[12]熊湘明,曲竹秋.大鼠高尿酸血症模型的建立[J].天津中医学院学报,2001,20(4)：28-29.
[13]宋文冲,王雅芹,陈超.虎参痛风胶囊对高尿酸血症及尿酸性肾病大鼠的影响[J].中国药理学通报,2004,20(3)：342-346.
[14]林穗芳.健脾固肾利湿法治疗高尿酸血症23例疗效观察[J].新中医,2004,36(10)：22-23.
[15]胡美兰.健脾化痰通络渗湿法治疗高尿酸血症40例疗效观察[J].云南中医中药杂志,2006,27(3)：15-16.
[16]熊湘明,曲竹秋,贾锡链.清热利湿益气活血法降血尿酸及对肾损害的保护作用[J].中国中西医结合急救杂志,2005,12(1)：27-30.
[17]华鸿宝.高尿酸血症的药物治疗[J].医师进修杂志,1998,21(6)：6.
[18]LehmannJM, LenhardJM, OliverBB, etal. Peroxisome Proliferal or aetivated receptors alpha and gamma are aetivated by indomethacin and other non—steroidal anti—inflammatory drugs. JBiolChem.1997,272:3406-3410.
[19]田财军,刘莹,陈宪海.痰毒与痛风.山东中医杂志,2001,20(3)：135.
[20]袁曙光,张秋才.急性痛风从痈论治.河北中医,2000,22(11)：837.
[21]王秀莲.痛风病本虚标实论治探讨.山东中医杂志,2001,20(4)：199.
[22]黄萌高.调脾益肾化湿泄浊法治疗痛风38例.实用中医药杂志,2001,17(5)：9.
[23]李平庸.痛风汤治疗急性痛风性关节炎64例.湖南中医杂志,2004,20(1)：42-43.
[24]王必中.浅述中医对痛风的认识及治疗.安徽中医学院学报,1992,(3)：12.
[25]高东祥,李荣秀,尹亚君教授辨治痛风病的经验.云南中医学院学报,2004,27(2)：44-45.
[26]赵恒侠.高尿酸血症与痰湿瘀浊综合征辨析.河南中医学院学报,2003,18(5)：41-42.
[27]张永生.姜良铎教授治疗痛风经验.北京中医药大学学报,2002,(2)：61-62.
[28]Corella D, Silla J, Ordovas JM, et al. Association of blood uric acid with other cardiovascular risk factors in the male working population in Valencia. Rev Clin Esp,1999,199:806-812.
[1]赵慧辉,王伟.病证结合证候模型研究基本思路.中华中医药杂志,2006,21(12)：762-764.
[2]刘涛,王伟.证候动物模型研究的思索.中华中医药杂志,2006,21(9)：550-51.
[3]富琦,陈信义.建立病证结合动物模型的新思路.中国中医药信息杂志,2003,10(9)：79-80.
[4]孙广仁,王洪武,高博等.COPD寒饮蕴肺证大鼠病证结合模型的建立.山东中医药大学学报,2007,31(3)：242-244.
[5]李敬林,王太一,王禄增等.2型糖尿病证病结合动物模型的研究.中国比较医学杂志,2007,17(8)：473-475.
[6]陈小野,邹世洁,张晓娟等.2种小鼠乳腺癌模型的证候属性研究.现代中西医结合杂志,2005,14(17)：2244-2245,2280.
[7]丰平,王学江.病证结合血瘀证动物模型研究.北京中医,2000,第6期：52-53.
[8]陈小野,邹世洁.大鼠CAG证病结合模型的造模方法和思路.实验动物科学与管理,2002,19(3)：35-37.
[9]倪量,王硕仁,吴爱明.部分缩窄大鼠腹主动脉致心室重构动物模型的病证结合研究.北京中医药大学学报,2007,30(4)：256-259.
[10]杨宇飞,马麟麟,许勇刚等.继发性红细胞增多症血瘀证病证结合动物模型的建立及清血颗粒的活血化瘀作用.中国中医基础医学杂志,2005,11(6)：446-448.
[11]张冰,刘小青等.鹌鹑高尿酸血症中医证候学研究.北京中医药大学报,2006,29卷(10)：676-678.
[12]孙景波,华荣等.用以药测证原理研究慢性肾衰大鼠模型的中医证候属性.现代中医药,2004,第2期.
[13]高碧珍,李延平,李灿东等.不同中医治法方药对高尿酸血症大鼠体重及生化指标的影响.中国中医药科技,2008,15(3)：180-181.
[14]高碧珍,李延平,李灿东等.不同方药对高尿酸血症大鼠模型黄嘌呤氧化酶及肾功能的影响.中华中医药杂志,2008,23(2)：97-99.
[15]屈会化,赵琰,曲荣波等.自发性高血压大鼠早期中医证候的研究.中医杂志,2008,49(5)：446-448.
[16]郭书文,孟庆刚.病证结合模型的研究思路.中医药学报,2001,29(1)：2～4.
[17]屈会化,赵琰,王庆国.自发性疾病动物模型的中医证候特征辨析思路与方法.中华中医药学刊,2007,25(12)：2506-2508.
[18]陈小野.证候动物模型诊断依据的设想与评价.中国医药学报,1987,2(1)：50-53.
[2]郑平东等.用腺嘌呤制作慢性肾功能衰竭动物模型.中华肾脏病杂志,1989,5(6)：342.
[3]王小京,李龙宫.比色法测定腺嘌呤氧化酶.生物化学与生物物理进展,1996,3(5)：65-70.
[4]迟秀梅等.海洛因对C6细胞嘌呤核苷酸分解代谢基因表达的影响.中国实验诊断学,2008,12(5)：589.
[5]阚幕洁等.吗啡对肠道嘌呤核苷酸分解代谢的影响.吉林大学学报,2004,30(2)：2009.
[6]苗志敏.痛风病学.2006,11.
[7]李宁,孙惠新,汪履秋治疗痛风经验撷萃.安徽中医临床杂志,1998,1(1)：32.
[8]张冰,刘小青等.鹌鹑高尿酸血症中医证候学研究.北京中医药大学报,2006,29(10)：676-678.
[9]孙景波,华荣等.用以药测证原理研究慢性肾衰大鼠模型的中医证候属性.现代中医药,2004,(2).
[10]高碧珍,李延平,李灿东等.不同中医治法方药对高尿酸血症大鼠体重及生化指标的影响.中国中医药科技,2008,15(3)：180-181.
[11]高碧珍,李延平,李灿东等.不同方药对高尿酸血症大鼠模型黄嘌呤氧化酶及肾功能的影响.中华中医药杂志,2008,23(2)：97-99.
[12]熊湘明,曲竹秋.大鼠高尿酸血症模型的建立[J].天津中医学院学报,2001,20(4)：28-29.
[13]宋文冲,王雅芹,陈超.虎参痛风胶囊对高尿酸血症及尿酸性肾病大鼠的影响[J].中国药理学通报,2004,20(3)：342-346.
[14]林穗芳.健脾固肾利湿法治疗高尿酸血症23例疗效观察[J].新中医,2004,36(10)：22-23.
[15]胡美兰.健脾化痰通络渗湿法治疗高尿酸血症40例疗效观察[J].云南中医中药杂志,2006,27(3)：15-16.
[16]熊湘明,曲竹秋,贾锡链.清热利湿益气活血法降血尿酸及对肾损害的保护作用[J].中国中西医结合急救杂志,2005,12(1)：27-30.
[17]华鸿宝.高尿酸血症的药物治疗[J].医师进修杂志,1998,21(6)：6.
[18]LehmannJM, LenhardJM, OliverBB, etal. Peroxisome Proliferal or aetivated receptors alpha and gamma are aetivated by indomethacin and other non—steroidal anti—inflammatory drugs. JBiolChem.1997,272:3406-3410.
[19]田财军,刘莹,陈宪海.痰毒与痛风.山东中医杂志,2001,20(3)：135.
[20]袁曙光,张秋才.急性痛风从痈论治.河北中医,2000,22(11)：837.
[21]王秀莲.痛风病本虚标实论治探讨.山东中医杂志,2001,20(4)：199.
[22]黄萌高.调脾益肾化湿泄浊法治疗痛风38例.实用中医药杂志,2001,17(5)：9.
[23]李平庸.痛风汤治疗急性痛风性关节炎64例.湖南中医杂志,2004,20(1)：42-43.
[24]王必中.浅述中医对痛风的认识及治疗.安徽中医学院学报,1992,(3)：12.
[25]高东祥,李荣秀,尹亚君教授辨治痛风病的经验.云南中医学院学报,2004,27(2)：44-45.
[26]赵恒侠.高尿酸血症与痰湿瘀浊综合征辨析.河南中医学院学报,2003,18(5)：41-42.
[27]张永生.姜良铎教授治疗痛风经验.北京中医药大学学报,2002,(2)：61-62.
[28]Corella D, Silla J, Ordovas JM, et al. Association of blood uric acid with other cardiovascular risk factors in the male working population in Valencia. Rev Clin Esp,1999,199:806-812.
[1]赵慧辉,王伟.病证结合证候模型研究基本思路.中华中医药杂志,2006,21(12)：762-764.
[2]刘涛,王伟.证候动物模型研究的思索.中华中医药杂志,2006,21(9)：550-51.
[3]富琦,陈信义.建立病证结合动物模型的新思路.中国中医药信息杂志,2003,10(9)：79-80.
[4]孙广仁,王洪武,高博等.COPD寒饮蕴肺证大鼠病证结合模型的建立.山东中医药大学学报,2007,31(3)：242-244.
[5]李敬林,王太一,王禄增等.2型糖尿病证病结合动物模型的研究.中国比较医学杂志,2007,17(8)：473-475.
[6]陈小野,邹世洁,张晓娟等.2种小鼠乳腺癌模型的证候属性研究.现代中西医结合杂志,2005,14(17)：2244-2245,2280.
[7]丰平,王学江.病证结合血瘀证动物模型研究.北京中医,2000,第6期：52-53.
[8]陈小野,邹世洁.大鼠CAG证病结合模型的造模方法和思路.实验动物科学与管理,2002,19(3)：35-37.
[9]倪量,王硕仁,吴爱明.部分缩窄大鼠腹主动脉致心室重构动物模型的病证结合研究.北京中医药大学学报,2007,30(4)：256-259.
[10]杨宇飞,马麟麟,许勇刚等.继发性红细胞增多症血瘀证病证结合动物模型的建立及清血颗粒的活血化瘀作用.中国中医基础医学杂志,2005,11(6)：446-448.
[11]张冰,刘小青等.鹌鹑高尿酸血症中医证候学研究.北京中医药大学报,2006,29卷(10)：676-678.
[12]孙景波,华荣等.用以药测证原理研究慢性肾衰大鼠模型的中医证候属性.现代中医药,2004,第2期.
[13]高碧珍,李延平,李灿东等.不同中医治法方药对高尿酸血症大鼠体重及生化指标的影响.中国中医药科技,2008,15(3)：180-181.
[14]高碧珍,李延平,李灿东等.不同方药对高尿酸血症大鼠模型黄嘌呤氧化酶及肾功能的影响.中华中医药杂志,2008,23(2)：97-99.
[15]屈会化,赵琰,曲荣波等.自发性高血压大鼠早期中医证候的研究.中医杂志,2008,49(5)：446-448.
[16]郭书文,孟庆刚.病证结合模型的研究思路.中医药学报,2001,29(1)：2～4.
[17]屈会化,赵琰,王庆国.自发性疾病动物模型的中医证候特征辨析思路与方法.中华中医药学刊,2007,25(12)：2506-2508.
[18]陈小野.证候动物模型诊断依据的设想与评价.中国医药学报,1987,2(1)：50-53.