黄芪甲苷对糖尿病模型大鼠造影剂肾损伤的保护作用

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目的 研究黄芪甲苷对糖尿病模型大鼠造影剂肾损伤的保护作用,并从炎性因子、抗氧化应激等方面探讨黄芪甲苷对造影剂肾损伤的保护机制.方法 Wistar大鼠70只,取10只设为正常对照组、其余大鼠以链脲佐菌素制备糖尿病大鼠模型.造模次日将大鼠随机分为模型对照组、阳性对照组[厄贝沙坦50 mg·(d·kg)-1]、造影剂损伤组和黄芪甲苷低、中、高[2.5、5、10 mg·(d·kg)-1]3个剂量组],均一次性给予60%泛影葡胺10 ml ·kg-1尾静脉注射.给药组每天灌胃给药1次,正常对照组、模型对照组、造影剂损伤对照组均灌胃给予等体积生理氯化钠溶液,每天1次,连续21d.比较各组大鼠血糖、肾脏肥大指数、尿素氮(BUN)、血肌酐(Cr)、尿微量白蛋白(UmAlb)、尿α1-微球蛋白(Uα1 MG)水平、24 h尿蛋白(UP24)等肾功能相关指标,比较各组血清白细胞介素-6(IL-6)水平,血清超氧化物歧化酶(SOD)活性、脂质过氧化代谢产物丙二醛(MDA)含量的改变,观察肾脏病理显微结构.结果 模型组大鼠血糖维持在较高水平、肾脏肥大指数、BUN、Cr、UP24、Um-Alb、Uα1-MG水平、血清IL-6较正常组明显升高(P<0.01),血清SOD活性低下,MDA含量增加(P<0.01).造影剂损伤组较模型组组各项指标均进一步恶化.黄芪甲苷干预组与造影剂损伤组相比,肾脏肥大指数、BUN、Cr、UP24、UmAlb、Uα1-MG、IL-6水平明显改善(P<0.01),血清SOD活性增强,MDA含量减少(P<0.01).结论 对糖尿病造影剂肾损伤大鼠,黄芪甲苷在改善肾功能基本指标的同时,可能通过降低炎性因子血清IL-6水平、提高机体抗氧化能力发挥其肾功能的保护作用.“,”Objective To investigate the effect of astragaloside Ⅳ(AsⅣ) on IL-6 and anti-oxidative stress in rats with diabetic radiocontrast media-induced nephropathy(RCIN).Methods Seventy Wistar rats were randomly divided into seven groups(n =10)..the normal control group,modlel control group,positive control group,radiocontrast media-induced injury group and low,middle and high dose of As Ⅳ groups.As Ⅳ 10,5,2.5 mg ·(d ·kg)-1 was given to the rats in As Ⅳ groups for 21 days,while the other groups were given the same volume of physiological saline.The fasting blood glucose (FBG),kidney weight/body weight,blood urea nitrogen,serum creatinine,and urine protein 24 h were measured by an automatic biochemical analyzer and urine microalbumin,Urinary α1-microglobulin,IL-6,SOD,and MDA were detected by different methods,while the physiological microstructure of the kidney was observed.Results FtBG,kidney weight/body weight,BUN,Cr,UP24,UmAlb and Uα1 MG ID6 were significantly increased in the model group compared with the normal group(P <0.01).Serum SOD activity was significantly decreased and MDA content was increased in the model group rats compared with the normal group(P <0.01).Each index further deteriorated in the radiocontrast media-induced injury group compared with the model control group.Kidney weight/body weight,BUN,Cr,UP24,UmAlb and Uα1-MG IL-6were significantly ameliorated in As Ⅳ groups compared with the radiocontrast media-induced injury group(P <0.01).Serum SOD activity significantly increased and MDA content decreased in the As Ⅳ group rats compared with the model group(P <0.01).Renal histological analysis indicated granulovacuolar deneneration,brush border thinning and exfoliation in tubular cells in radiocontrast media-induced injury group rats.Conclusion As Ⅳ could improve renal function in rats with diabetic RCIN by reducing IL-6 and enhancing anti-oxidative capacity.
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