白藜芦醇对大鼠肾脏缺血再灌注损伤的保护作用

摘要

To explore the underlying protection and mechanism of RSV in renal ischemia reperfusion injury (IRI).The model of IRI was induced by clamping the left renal pedicles with right nephrectomy.SD rats were randomly divided into Sham group(Sham),Renal ischemia reperfusion injury group (IRI),and Resveratrol pretreatment group (RSV).The morphology of kidney was exanimed by HE;The expression of Cr and BUN were measured by ELISA;TUNEL was used to examine the cell apoptosis;The expression of SIRT1,p53,Acetylp53,Bax,BCL-2,PUMA-α and cytochrome c were evaluated by Western blot analysis.The results showed RSV pretreatment can significantly decrease the expression of TUNEL,BUN,Cr,Acetyl 53,PUMA-α and Bax by increaseing the expression of SIRT1 and BCL-2.Moreover,RSV pretreatment can also attenuate the change of morphology of kidney and the transcolation of cytochrome c,which indicated RSV pretreatment can protect kidney against ischemia reperfusion injury by suppressing apoptosis.The mechanism was associated with attenuating Acetylp53 by activating SIRT1.%探讨白藜芦醇对大鼠肾脏缺血再灌注损伤(renal ischemia reperfusion injury,IRI)的保护作用及作用机制.通过血管夹夹闭左侧肾蒂,并去除右肾的方法构建大鼠IRI模型.将大鼠随机分为假手术组(Sham)、肾脏缺血/再灌注损伤组(IRI)和白藜芦醇低中高剂量组(RSV).利用ELISA检测各组血清尿素氮(blood urea nitrogen,BUN)和血清肌酐(Creatinine,Cr);HE染色检测肾脏病理形态;TUNEL法检测肾脏细胞凋亡;免疫印迹检测沉默信息调节因子1(SIRT1)、p53、乙酰化p53(Acetyl 53)、B细胞淋巴因子2(BCL-2)、Bcl-2相关X蛋白(Bax)和p53正向细胞凋亡调控因子(PUMA-α)表达以及细胞色素C迁徙.结果显示白藜芦醇预处理可增加SIRT1和BCL-2表达,减少BUN、Cr、Acetyl 53、PUMA-α、Bax和TUNEL的表达.此外,白藜芦醇还可减少肾脏病理形态改变和细胞色素C迁徙,但对p53表达无影响.提示白藜芦醇预处理可通过抗凋亡作用减轻肾脏缺血再灌注损伤,其作用机制可能与激活SIRT1抑制p53乙酰化相关.