白藜芦醇对2型糖尿病大鼠肾脏的保护作用及机制探讨

摘要

Objective To observe the protective effect of resveratrol ( Res) on the kidney of rats with type 2 diabetes mellitus and to explore the underlying mechanism .Methods During 40 SD rats, 16 rats were fed with normal diet (con-trol group and blank group, 8 rats in each group) and 24 rats were fed with high-fat diet for 8 weeks, and then 40 mg/kg streptozotocin (STZ) were injected into the 24 rats to make the type 2 diabetes mellitus models.After that, 16 model rats were selected and were randomly divided into the observation group and model group .Rats in the observation group and control group were treated with 10 mg/( kg · d) Res intragastrically and the model group and blank group with the same volume of 1%sodium carboxymethyl cellulose , once a day and for 8 weeks.The fasting blood glucose (FBG), blood lipid ( TG) , cholesterol ( TC) , kidney weight/body weight ( Kw/Bw) and 24 h urine protein were assayed , and the pathologic changes of renal tissues were observed .The expression of CD68 and α-SMA was detected by immunohistochemistry .The expression of transforming growth factor-β1 ( TGF-β1 ) , Smad3 and phospho-Smad3 was detected by Western blotting .Re-sults The 24 h urine protein, FBG, TC, TG and Kw/Bw of the observation group were lower than those of the model group (all P<0.01).The 24 h urine protein, FBG, TC, TG and Kw/Bw of the model group were higher than those of the blank group and the control group (all P<0.01).The pathologic changes of kidney tissues in the observation group were less than those of the model group , and the model group was more than that of the blank group .The expression of α-SMA and CD68 in the kidney tissues of the observation group was lower than that of the model group (all P<0.01), and the ex-pression of α-SMA and CD68 in the kidney tissues of the model group was lower than that of the blank group and the control group (all P<0.01).The expression of TGF-β1 and phospho-Smad3 in the observation group was lower than that of the model group (all P<0.01), and the expression of TGF-β1 and phospho-Smad3 in the model group was lower than that of the blank group and the control group (all P<0.01).Conclusion Res protects the kidney function of type 2 diabetic rats, which may be related to the inhibition of TGF-β1/Smad3 signaling pathway .%目的：观察白藜芦醇（Res）对2型糖尿病大鼠肾脏的保护作用，并探讨其作用机制。方法40只SD大鼠分别予普通饲料喂养16只（对照组、空白组各8只）和高脂高糖饲料喂养24只，喂养8周后高脂高糖喂养的大鼠一次性腹腔注射链脲佐菌素40 mg／kg制作2型糖尿病模型，取16只随机分为观察组、模型组各8只。观察组和对照组予10 mg／（kg· d） Res，模型组和空白组予等量的1％羧甲基纤维素钠，每日灌胃1次，连续8周。比较各组空腹血糖（FBG）、TG、TC、肾脏质量指数（Kw／Bw）、24 h尿蛋白定量。 PAS染色观察肾脏组织病理学变化，免疫组化法检测肾脏组织CD68和α平滑肌肌动蛋白（α-SMA），Western blot法检测转化生长因子β1（ TGF-β1）、Smad3和磷酸化Smad3蛋白。结果观察组24 h尿总蛋白、FBG、TC、TG、Kw／Bw均低于模型组，P均＜0．01；模型组24 h尿总蛋白、FBG、TC、TG、Kw／Bw均高于空白组、对照组，P均＜0．01。肾脏组织病理改变为观察组轻于模型组，模型组重于空白组、对照组。观察组肾脏组织α-SMA、CD68的表达均低于模型组，P均＜0．01；模型组肾脏组织α-SMA、CD68表达均低于空白组、对照组，P均＜0．01。观察组TGF-β1、磷酸化Smad3蛋白的相对表达量明显低于模型组、对照组，P均＜0．01；模型组TGF-β1、磷酸化Smad3蛋白的相对表达量明显低于空白组，P均＜0．01。结论 Res对2型糖尿病大鼠的肾脏功能有保护作用，可能与抑制TGF-β1／Smad3信号通路有关。