依那普利对大鼠糖尿病模型肾内炎症的干预作用及可能机制  

Effects of enalapril on inflammation in kidney of diabetic rats and its possible mechanism

作　　者：钱浩[1] 吴永贵[1] 林辉[1] 赵珉[1] 周典[1] 卢文[1] 张伯科[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,安徽合肥230022

出　　处：《中国病理生理杂志》2005年第5期945-948,共4页Chinese Journal of Pathophysiology

基　　金：安徽省自然科学基金资助项目(No.01043703);安徽省卫生厅科学研究基金项目(No.2002A004)

摘　　要：目的探讨依那普利对大鼠糖尿病模型肾内炎症的干预作用及可能机制。方法建立STZ诱导的单侧肾切除大鼠糖尿病模型,随机分对照组、糖尿病组与依那普利给药组,每组10只。8周末检测24h尿白蛋白排泄率(AER)、肾组织与尿丙二醛(MDA)含量及肾组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)与谷胱甘肽过氧化物酶(GSH-PX)活性。应用PAS染色观察肾小球病理组织学指标;免疫组织化学方法检测肾组织ED-1(巨噬细胞表面标志)及单核细胞趋化蛋白-1(MCP-1)与细胞间粘附分子-1(ICAM-1)表达。结果依那普利给药组大鼠肾重、肾重/体重、AER与肾小球面积、肾小球容积及系膜区面积明显低于模型组(P<0.05,P<0.01);模型组肾组织和尿MDA含量明显高于对照组(P<0.01),肾组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)与谷胱甘肽过氧化物酶(GSH-PX)活性明显低于对照组(P<0.05,P<0.01),依那普利可明显缓解这些变化(P<0.05);模型组肾小球ED-1阳性细胞数及MCP-1、ICAM-1表达明显高于对照组(P<0.01),依那普利给药组肾小球巨噬细胞浸润及MCP-1表达明显低于模型组(P<0.05),ICAM-1表达无明显差异。结论依那普利对糖尿病大鼠肾脏保护作用机制部分可能与抑制肾内炎症有关。AIM: To investigate the effects and mechanism of enalapril on nephritis of diabetic mice. METHODS: Diabetes was induced by injection of streptozotocin after uninephrectomy. Rats were randomly divided into three groups: control, diabetes, diabetes treated with enalapril (10 mg·kg^-1 ·d^-1 by gavage). 8 weeks after STZ injection, urine albumin excretion rate (AER) were measured, and glomerular morphology were observed by light microscopy. The levels of malonyldialdehyde (MDA) in renal tissue and urine as well as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) in renal tissue were determined. Immunohistochemistry for ED-1 (macrophage marker), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) were performed by streptavidin-biotin complex (SABC) technique. RESULTS: Increased kidney weight, ratio of kidney weight to body weight, AER and expansion of mesangial as well as tuft areas on histological examination of the kidney were significantly attenuated by the treatment of enalapril (P<0.05, P<0.01). Elevated MDA levels in renal tissue and urine as well as decreased SOD, CAT, GSH-PX activities in renal tissue were also remitted by enalapril (P<0.05). Increased glomerular macrophage recruitment and expression of MCP-1 was significantly inhibited by enalapril (P<0.05). However, elevated ICAM-1 expression was not reduced by enalapril in glomerulus in diabetic rats. CONCLUSION: Possible mechanism of renal protection of enalapril may be at least partly related with suppression of inflammation in kidney of diabetic rats.

关 键 词：糖尿病肾病 炎症 依那普利 

分 类 号：R363[医药卫生—病理学]