文章摘要
印媛君,郭燚,唐比强,等.SIRT1/SIRT3轴在糖尿病肾病肾小管-间质损伤中的作用研究[J].浙江中医药大学学报,2021,(5):460-466, 474.
SIRT1/SIRT3轴在糖尿病肾病肾小管-间质损伤中的作用研究
Role of SIRT1/SIRT3 Axis in Tubulointerstitial Injury of Diabetic Nephropathy
投稿时间:2020-08-17  
DOI:10.16466/j.issn1005-5509.2021.05.005
中文关键词: 糖尿病肾脏疾病  ZDF大鼠  肾小管-间质损伤  线粒体自噬  SIRT1  SIRT3
英文关键词: diabetic kidney disease  ZDF rat  tubulointerstitial injury  mitophagy  SIRT1  SIRT3
基金项目:国家自然科学基金项目(81774177);浙江省中医药科技计划项目(2020ZB063)
作者单位E-mail
印媛君 浙江中医药大学 杭州 310053  
郭燚 浙江中医药大学 杭州 310053  
唐比强 浙江中医药大学 杭州 310053  
毛稳 浙江中医药大学 杭州 310053  
赵娜 浙江中医药大学 杭州 310053  
杜月光 浙江中医药大学 杭州 310053 duyueguang@163.com 
摘要点击次数: 56
全文下载次数: 33
中文摘要:
      [目的]探讨沉默信息调节因子1(silent information regulator 1,SIRT1)/SIRT3轴在Zucker糖尿病肥胖(Zucker diabetic fatty,ZDF)大鼠肾小管-间质损伤中的作用。[方法]将16只清洁级雄性ZDF大鼠随机分为模型组和SIRT1过表达组,另将ZL大鼠8只设为正常组。建模成功后,分别检测尿蛋白(urinary protein,UP)、尿微量蛋白(urinary albumin,U-ALB)、空腹血糖(fasting blood glucose,FBG)和血肌酐(serum creatinine,Scr)水平。苏木素-伊红(hematoxylin-eosin,HE)染色和Masson染色后,镜下观察肾组织病理改变。以实时定量聚合酶链式反应(Real-time polymerase chain reaction,Real-time PCR)检测SIRT1和SIRT3 mRNA表达;Western blot测定肾组织SIRT1、SIRT3、微管相关蛋白轻链3(microtubule-associated protein light chain 3,LC3)、p62和Parkin蛋白表达;免疫组化检测α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)表达。[结果]与正常组比较,模型组FBG、UP、U-ALB和Scr水平均明显升高(P<0.01);SIRT1和SIRT3 mRNA表达下降(P<0.05),SIRT1、LC3Ⅱ/Ⅰ和Parkin等蛋白表达明显降低(P<0.01),p62蛋白表达明显升高(P<0.05);肾间质α-SMA阳性细胞数增加(P<0.01);肾小球呈局灶性纤维化,局灶性肾小管上皮细胞空泡变、坏死及萎缩,出现管型,肾间质纤维增生。与模型组比较,SIRT1过表达组FBG、Scr和U-ALB水平均降低(P<0.01,P<0.05);SIRT1和SIRT3 mRNA表达增加(P<0.05,P<0.01);SIRT1、SIRT3、LC3Ⅱ/Ⅰ和Parkin等蛋白表达明显升高(P<0.05,P<0.01),p62蛋白表达明显降低(P<0.01);肾间质α-SMA阳性细胞数减少(P<0.01);肾脏病理改变减轻。[结论]SIRT1/SIRT3信号轴可能通过改善线粒体自噬,减轻肾小管-间质损伤,对肾脏起到保护作用。
英文摘要:
      [Objective]To investigate the role of silent information regulator 1(SIRT1)/SIRT3 axis in tubulointerstitial injury in Zucker diabetic fatty(ZDF) rats.[Methods] Sixteen male ZDF rats of cleaning grade were randomly divided into model group and SIRT1 over-expression group;and eight ZL rats were used as normal group.After successful modeling, the levels of urinary protein(UP), urinary albumin(U-ALB), fasting blood glucose(FBG) and serum creatinine(Scr) were detected. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes of renal tissue.The protein levels of SIRT1,SIRT3, microtubule-associated protein light chain3(LC3), p62 and Parkin in the renal tissues were determined by Western blot. The mRNA expression of SIRT1 and SIRT3 was analyzed by Real-time polymerase chain reaction(Real-time PCR). The protein levels of α-smooth muscle actin(α-SMA) was detected by immunohistochemistry.[Results] Compared with normal group, FBG, UP, U-ALB and Scr were obviously increased in model group(P<0.01); the mRNA expression of SIRT1and SIRT3 was decreased(P<0.05); the protein levels of SIRT1,LC3Ⅱ/Ⅰ and Parkin were decreased(P<0.01), while the protein level of p62 was increased(P<0.05). The number of α-SMA positive cells in renal interstitial were obviously increased(P<0.01). Glomerular and renal interstitial focal fibrosis,focal renal tubular epithelial cell vacuolation,necrosis,shedding and atrophy,and renal interstitial fibrosis were observed in model group.Compared with model group,FBG was obviously decreased(P<0.01), Scr and U-ALB were also decreased in SIRT1 over-expression group(P<0.05); the mRNA expression of SIRT1 and SIR3 was increased(P<0.05, P<0.01); the protein levels of SIRT1,SIRT3,LC3Ⅱ/Ⅰand Parkin were increased(P<0.05,P<0.01), while the protein level of p62 was decreased in SIRT1 over-expression group(P<0.01); and the number of α-SMA positive cells in renal interstitial were obviously decreased(P<0.01).The renal damage was attenuated.[Conclusion]SIRT1/SIRT3 signal axis may protect renal function by improving mitophagy and then alleviating tubulointerstitial injury.
查看全文   查看/发表评论  下载PDF阅读器
关闭