霉酚酸酯对局灶节段性肾小球硬化(FSGS)治疗作用的研究

目的:用霉酚酸酯(MMF)对以阿霉素肾病大鼠建立的局灶节段性肾小球硬化(FSGS)模型,进行干预,检测结缔组织生长因子(CTGF)的表达,研究霉酚酸酯对FSGS的治疗作用,并探讨作用机理。方法:SD大鼠18只,分为对照组、阿霉素肾病组、MMF治疗组(每组大鼠6只)。肾病组、治疗组大鼠尾静脉一次性注入阿霉素7.5mg/kg,对照组大鼠尾静脉注入等量生理盐水。治疗组于第6周起MMF 20mg.kg-1.d-1混悬于1mL蒸馏水灌胃,其他组等量蒸馏水灌胃。第10周处死所有大鼠,观察肾组织病理变化,并以免疫组织化学、Western blot方法检测肾组织CTGF蛋白水平。结果:阿霉素肾病组大鼠较对照组大鼠肾小球系膜及基质明显增生,免疫组织化学染色及western blot显示肾小球和肾小管区CTGF蛋白表达明显上升(P<0.05),霉酚酸酯治疗组肾小球系膜和基质增生较肾病组明显减轻,肾小球和肾小管区CTGF蛋白表达明显低于肾病组(P<0.05)。结论:霉酚酸酯可以减轻肾脏间质纤维化病变,机理与抑制CTGF的表达有关。

Effects of Mycophenolate Mofetil on Focal Segmental Glomerulosclerosis

Objective:To detect the changes of connective tissue growth factor(CTGF) in adriamycin nephropathy rats,study the effects of mycophenolate mofetil on Focal segmental glomerulosclerosis,and investigate its possible mechanisms.Methods: 18 SD rats were randomly divided into three groups: control group(CG,n=6),FSGS model group(FG,n=6),MMF treated group(TG,n=6).Rats in MG and TG were given adriamycin 7.5mg/kg through vena caudalis.At the same time,an equal volume of normal saline was given to the rats in CG by the same method.The rats in TG received MMF 20mg·kg~(-1)·d~(-1) by daily gastric gavage from the 6th week.Renal pathological changes were evaluated at the 10th week.The expression of connective tissue growth factor(CTGF) were analyzed by immunohistochemistry and western blot.Results: The proliferation of the mesangial cells and the accumulation of the extracellular matrix in FG were more remarkable than that in CG.The expression of CTGF protein increased significantly(P<0.05).The proliferation of the TG rats were ameliorated,the expression of CTGF decreased markedly in TG rats(P<0.05).Conclusions: MMF can ameliorate kidney interstitial fibrosis,and the effect is related to decrease of CTGF expression.