| 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,2021,45(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 |
| 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) |
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| 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. |
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