白藜芦醇改善糖尿病大鼠肾脏炎症损伤  

Amelioration of Diabetic Nephropathy in Rats by Resveratrol:Involvement of Anti-Inflammatory Effect

作　　者：郑晓英[1] 朱深银[1] 周远大[1] 曹燕妮[1] 董杰[1] 李娟[1] 

机构地区：[1]重庆医科大学附属第一医院药学部,重庆400016

出　　处：《中国药学杂志》2014年第11期919-924,共6页Chinese Pharmaceutical Journal

基　　金：重庆市医学科研计划项目(2009-2-408)

摘　　要：目的研究白藜芦醇(resveratrol,Rev)对糖尿病大鼠肾脏炎症损伤的保护作用。方法高糖高脂饲料喂养大鼠4周后,腹腔注射链脲佐菌素(40 mg·kg-1),建立糖尿病大鼠模型,继续高脂高糖饲养,同时白藜芦醇(50 mg·kg-1·d-1)灌胃给药32周后,分别检测各组大鼠体重、血糖、甘油三酯(TG)、总胆固醇(TC)、尿素氮(BUN)、肌酐(Scr)、胱抑素C(CysC)、24 h尿蛋白(24-hour urine protein,UP 24 h)等指标,酶联免疫法测定血清白介素1β(IL-1β)、白介素6(IL-6)、细胞间黏附分子-1(ICAM-1)水平,伊文思蓝(Evans blue,EB)法测定肾脏血管通透性,PAS染色观察肾脏组织的病理学改变,免疫组化染色观察肾脏细胞间黏附分子-1蛋白表达,采用RT-PCR测定肾脏组织中细胞间黏附分子-1 mRNA表达,Western blot检测肾脏组织细胞间黏附分子-1蛋白表达。结果白藜芦醇能显著控制糖尿病大鼠体重增加、降低甘油三酯和总胆固醇及血糖水平,能明显降低血清尿素氮、肌酐、胱抑素C水平,减少24 h尿蛋白和血清白介素1β、白介素6、细胞间黏附分子-1水平(P<0.05),显著降低肾脏血管通透性(P<0.05),减轻肾脏病理损伤,下调肾脏组织细胞间黏附分子-1 mRNA及蛋白表达(P<0.05)。结论白藜芦醇通过降低糖尿病大鼠血糖和血脂水平、抑制促炎细胞因子生成,从而改善糖尿病大鼠肾功能和肾脏炎症损伤。OBJECTIVE To observe the protective effect of resveratrol （Rev） on diabetic nephropathy in rats with inflammation impairment. METHODS Male rats were divided into two groups and fed with commercially available normal pellet diet （NPD） or inhouse prepared high-fat diet （HFD） , respectively. After 4 weeks of dietary feed, the rats from HFD group were injected intraperitoneally with low dose of streptozotocin （STZ） （40 mg· kg^-1 ）. Half of the rats from both groups were administered with a dose of Rev（50 mg· kg^-1 · d^-1 ）for 32 weeks. The rats were allowed to continue to be feed on their respective diets until the end of the study. After 32 weeks, the body weight, levels of FPG, TC, TG, BUN, SCr, Cys C, and urine protein and kidney vascular permeability were assayed ; the contents of IL-1 β, IL-6 and ICAM-1 in serum were detected by ELISA ; the vascular permeability of kidney was detected by Evans blue ; glomerular morphological analysis was performed in PAS stained pathological section ; the levels of ICAM-1 mRNA and the expression of ICAM-1 in kidney were detected by RT-PCR and Immunohistochemistry and Western blot. RESULTS Rev had remarkably suppressed weight gain and lowered levels of FPG, TC, TG, BUN, SCr, Cys C, IL-1β, IL-6 and ICAM-1 in serum （P 〈 0. 05） , decreased urine protein （P 〈 0. 05）, and reduced kidney vascular permeability （ P 〈 0. 05 ）. Increased indices for glomerular injury were significantly ameliorated by Rev treatment （P 〈0. 05）. The expression of ICAM-1 mRNA was markedly up-regulated in the kidneys of diabetic rats, which was effectively suppressed by Rev treatment （P 〈 0. 05 ）. Western blot and immunohistoehemistry analysis showed that the expression of ICAM-1 was reduced significantly by Rev treatment. CONCLUSION Rev can ameliorate diabetic nephropathy damage in rats, and the protection role may be attributed to its effect to lower lipid and glucose levels in serum and inhibit inflammation in kidney.

关 键 词：白藜芦醇 糖尿病肾病 大鼠 炎症 细胞间黏附分子-1 血管通透性 

分 类 号：R965[医药卫生—药理学]