| 张泓,许明旺,熊亮,文秀英,刘丽芳,刘浩,黄文凡,陈爱萍.贞清方与地龙对2型糖尿病大鼠肾组织TGF-β1及PAI-1表达的影响[J].中国中西医结合杂志,2011,31(7):967-972 |
| 贞清方与地龙对2型糖尿病大鼠肾组织TGF-β1及PAI-1表达的影响 |
| Effects of Zhenqing Recipe and Earthworm on the Expressions of Transforming Growth Factor-β1 and Plasminogen Activator Inhibitor 1 in Renal Tissues of Type 2 Diabetic Rats |
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| DOI： |
| 中文关键词: 贞清方 地龙 糖尿病肾病 转化生长因子β1 纤溶酶原激活物抑制剂-1 |
| 英文关键词:Zhenqing Recipe earthworm diabetic nephropathy transforming growth factor-β1 plasminogen activator inhibitor-1 |
| 基金项目:国家自然科学基金资助项目(No.30672730) |
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| 中文摘要: |
| 目的研究中药复方贞清方和方中的地龙对糖尿病大鼠肾组织转化生长因子β1(TGF-β1)和纤溶酶原激活物抑制剂-1(PAI-1)表达的影响。方法通过高糖高脂饮食加腹腔注射小剂量链脲佐菌素建立2型糖尿病大鼠模型,随机分为:模型组、贞清方组和地龙组,并设立正常对照组,每组10只。贞清方组给予贞清方提取液24g/(kg·d)灌胃,地龙组给予地龙提取液2·6g/(kg·d)灌胃,正常对照组及模型组给予等体积蒸馏水灌胃,均每天1次,连续治疗8周。观察大鼠空腹血糖(FBG)、血清PAI-1、24h尿微量白蛋白(UAE)和内生肌酐清除率(CCr);过碘酸雪夫(PAS)染色后光镜下观察肾组织结构变化,并通过免疫组化法分析TGF-β1、PAI-1的表达;利用RT-PCR和Westernblot分别检测肾皮质TGF-β1、PAI-1 mRNA和蛋白表达水平。结果与正常对照组比较,模型组大鼠FBG、血清PAI-1、UAE、TGF-β1和PAI-1 mRNA及蛋白表达均明显升高,CCr明显降低,差异有统计学意义(P<0·01)。与模型组比较,贞清方组FBG、血清PAI-1、UAE均明显下降(P<0·01),CCr明显升高(P<0·05);地龙组FBG无明显降低,血清PAI-1、UAE均下降(P<0·05,P<0·01),CCr升高(P<0·05);贞清方组优于地龙组。贞清方组和地龙组肾组织病理学变化程度减轻。贞清方组和地龙组TGF-β1和PAI-1 mRNA及蛋白表达较模型组降低(P<0·05,P<0·01),以贞清方组更显著。结论贞清方和地龙在2型糖尿病大鼠肾病早期应用可保护肾脏,其机制可能与抑制TGF-β1表达,导致PAI-1表达下调有关。贞清方的作用强于单味药地龙。 |
| 英文摘要: |
| Objective To study the effects of Zhenqing Recipe(ZQR) and earthworm on the expressions of transforming growth factor-β1(TGF-β1) and plasminogen activator inhibitor-1(PAI-1) in renal tissues of type 2 diabetes mellitus(T2DM) rats.Methods The T2DM model rats induced by high sucrose/fat feeding and low dose streptozotocin injecting were randomly divided into the model group,the ZQR group,and the earthworm group.A normal control group was also set up.ZQR extract was given at the daily dose of 24 g/kg body weight by gastrogavage to rats in the ZQR group.The earthworm extract was given at the daily dose of 2.6 g/kg body weight by gastrogavage to rats in the earthworm group.Equal volume of distilled water was given to rats in the normal control group and the model group by gastrogavage.The medication was once daily for 8 successive weeks.The fasting blood glucose(FBG),serum PAI-1,24-h urinary albumin excretion(UAE),and endogenous creatinine clearance rate(CCr) were detected.The structural changes of renal tissues stained with Periodic Acid-Schiff were observed by light microscope.The expressions of TGF-β1 and PAI-1 were analyzed by immunohistochemistry.And the mRNA and protein expressions of TGF-β1 and PAI-1 in the renal cortex were detected by Real-time PCR and Western blot respectively.Results Compared with the normal control group,the FBG,serum PAI-1,UAE,the mRNA and protein expressions of TGF-β1 and PAI-1 significantly increased in the model group,and CCr obviously decreased(P<0.01).Compared with the model group,FBG,serum PAI-1,UAE obviously decreased(P<0.01) and CCr obviously increased(P<0.05) in the ZQR group.FBG was not obviously lowered in the earthworm group.The serum PAI-1 and UAE both decreased obviously(P<0.05,P<0.01) and CCr increased(P<0.05) in the earthworm group.The effects of ZQR were superior to the earthworm.The renal pathological changes got improved in the ZQR group and the earthworm group.The mRNA and protein expressions of TGF-β1 and PAI-1 significantly decreased in the ZQR group and the earthworm group,especially in the ZQR group.Conclusions Early application of ZQR and earthworm in treatment of T2DM rats with nephropathy was effective in protecting the kidney.Its mechanism may possibly be correlated with inhibition of TGF-β1 expression,resulting in down-regulation of PAI-1 expression.ZQR showed better effects than earthworm. |
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