依那普利联合霉酚酸酯对大鼠糖尿病肾脏结缔组织生长因子表达的影响

Effect of the combination of enalapril and mycophenolate mofetil on the expression of connective tissue growth factor in kidney in diabetic rats

目的探讨依那普利联合霉酚酸酯(MMF)对大鼠糖尿病肾脏结缔组织生长因子(CTGF)表达的影响。方法建立单侧肾切除链脲佐菌素(STZ)诱导的糖尿病模型。8周后观察24h尿白蛋白排泄率(AER)的变化,并行PAS染色肾小球与肾小管-间质病理观察;应用免疫组化方法检测肾组织CTGF蛋白表达。结果各给药组均可抑制糖尿病大鼠AER增加及肾小球病理结构损害(P<0.05,0.01),联合组尚可明显减轻糖尿病肾小管-间质损伤指数(P<0.05);糖尿病大鼠肾小球与肾小管-间质CTGF蛋白表达明显高于对照组,各给药组肾组织CTGF蛋白表达均明显低于模型组(P<0.05),其中以联合组最明显(P<0.01)。结论依那普利联合MMF对糖尿病肾脏有明显保护作用,其机制部分与抑制糖尿病肾组织CTGF过高表达有关。

Objective To study the effect of combined enalapril and mycophenolate mofetil （MMF） on the expression of connective tissue growth factor（CTGF） in the kidney in diabetic rats. Methods Diabetes was induced by injecting streptozotocin after uninephrectomy. 24 h urinary albumin excretion rate （AER） and renal tissue morphology were observed by light microscopy after 8 weeks. Expression CTGF protein was performed by immunohistochemistry method in the kidney. Results Diabetes was associated with a considerable increase in AER. Both enalapril and MMF retarded the increase in albuminuria, which was nearly completely abrogated by combination therapy. Glomerular volume in diabetic rats was attenuated by treatment with enalapril or MMF and further reduced by the combination of the two. Increased tubulointerstitial injury index was not decreased by enalpril or MMF treatment and reduced by the combination therapy in both cases. Overexpression of CTGF protein observed in glomeruli and tubulointerstitium of diabetic rats was attenuated by enalapril or MMF to a similar lever and further reduced by the combination of the two. Conclusion The combination of enalapril and MMF confers superiority over monotherapies on renoprotection, which mechanism may be at least partly correlated with synergetic suppression on overexpression of CTGF.