依那普利联合灯盏花素对糖尿病大鼠肾脏保护作用及机制  

Renoprotective effects of the combination of enalapril and breviscapine and their mechanism in diabetic rats′ kidney

作　　者：齐向明[1] 吴永贵[1] 吴国仲[1] 汪学龙[2] 沈际佳[2] 张伯科[1] 郝丽[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,合肥市230022 [2]安徽医科大学病原微生物教研室

出　　处：《中华老年医学杂志》2006年第1期53-57,共5页Chinese Journal of Geriatrics

基　　金：安徽省自然科学基金资助项目(01043703)

摘　　要：目的探讨依那普利联合灯盏花素对大鼠糖尿病肾脏保护作用及机制。方法大鼠随机分5组:对照组、糖尿病组、依那普利给药组、灯盏花素给药组及依那普利与灯盏花素联合给药组。8周后观察肾组织病理形态学变化,检测尿白蛋白排泄率(AER)、肾组织尿丙二醛(MDA)含量及肾组织蛋白激酶(PKC)活性;应用Western杂交检测肾组织PKC蛋白表达,免疫组化方法检测肾组织转化生长因子(TGF)β1蛋白表达。结果各给药组均可抑制糖尿病大鼠AER增加及肾组织病理结构损害,联合组优于单独给药组;对肾组织及尿MDA含量增加的抑制作用联合组也优于单给药组;各给药组均可抑制肾组织PKC活性与表达,以联合组最明显;糖尿病大鼠肾小球与肾小管-间质TGFβ1蛋白表达明显高于对照组,各给药组肾组织TGFβ1蛋白表达明显低于模型组,其中以联合组最明显。结论依那普利与灯盏花素联合给药对糖尿病肾脏保护作用优于任一单给药组,其机制部分与其对肾组织氧化应激增加、PKC激活及TGFβ1表达有协同抑制作用有关。Objective To assess renoprotective effects of the combination of enalapril and breviscapine and their mechanism in STZ-induced diabetic rats＇ kidney. Methods Rats were randomly separated into five groups： control, diabetes, diabetes treated with enalapril, diabetes treated with breviscapine, and diabetes treated with combined enalapril and breviscapine. Urinary albumin excretion rate（UAER）and the levels of MDA in renal tissue and urine as well as activities and expression of protein kinase C（PKC）in renal tissue were determined, and renal tissue morphology were observed by light microscopy after 8 weeks treatment. Expression of TGF β1 protein was performed by immunohistochemistry method. Results Increased UAER and kidney pathologic injury were attenuated by treatment with either enalapril or breviscapine and further reduced by the combination of the two. Elevated MDA levels in renal tissue and urine were reduced by enalapril or breviscapine and, more effectively, by combined enalapril and breviscapine. PKC activities and expression were higher in renal tissue of diabetic rats than those of the control group, which were reduced by both monotherapies, and further abrogated by combination therapy in both cases. Overexpression of TGF β1 protein observed in glomeruli and tubulointerstitium of diabetic rats were attenuated by enalapril or breviscapine to a similar level and further reduced by the combination of the two. Condusions The combination of enalapril and breviscapine confers superiority over monotherapies on renoprotection, which mechanism may be at least partly correlated with synergestic suppressions of the increased oxidative stress and PKC activities as well as overexpression of TGF β1 in renal tissue.

关 键 词：糖尿病肾病 蛋白激酶C 灯盏细辛 依那普利 转化生长因子β1 

分 类 号：R587.2[医药卫生—内分泌]