胰岛素降糖治疗对糖尿病肾病大鼠自噬的影响  

Effects of autophagy in the process of diabetic nephropathy

作　　者：刘楠[1] 钟良宝[1] 张瑞城[1] 梁海琴[1] 丁莉莉[1] 

机构地区：[1]海南医学院附属医院肾内科

出　　处：《临床肾脏病杂志》2015年第8期502-505,共4页Journal Of Clinical Nephrology

基　　金：海南省自然科学基金(NO.813235)

摘　　要：目的了解自噬在糖尿病肾病大鼠肾小球的表达情况，观察胰岛素降糖治疗对糖尿病肾病大鼠足细胞自噬的影响，探讨自噬在糖尿病肾病进程中的作用。方法选择50只雄性wistar大鼠，适应性喂养1周后随机选10只作为空白对照组（A组），另外40只大鼠进行链脲佐菌素（streptozotocin，STZ）诱导，腹腔注射STZ制备糖尿病动物模型。造模成功后将40只糖尿病大鼠随机分为2组（B组和C组），每组各20只；B组给予等量柠檬酸缓冲液皮下注射，C组每天根据血糖水平给予胰岛素1．5U／kg皮下注射，连续注射4周。4周后收集24h血、尿标本查尿素氮、肌酐、血糖，肾脏组织送病理PAS染色观察肾组织病理改变，透射电镜观察肾小球足细胞足突改变，Western blot检测自噬标志物LC3Ⅰ／Ⅱ表达。结果与A组相比，B、C组大鼠24h尿白蛋白、血糖均升高明显（P〈0．01），PAS染色发现肾小球基膜增厚，系膜区增宽，基质增多，电镜下足细胞足突增宽、融合，自噬活化标志物LC3-Ⅱ／LC3-Ⅰ值明显下降（P〈0．01）。与B组比，C组大鼠肾小球病理变化有所改善，足细胞和自噬体数量增多，细胞器损伤减轻，LC3-Ⅱ／LC3-Ⅰ值上调（P〈0．01）。结论糖尿病肾病大鼠肾小球自噬水平降低，胰岛素处理糖尿病肾病大鼠可上调自噬水平，并可减轻肾小球病理改变和足细胞损伤，提示自噬水平增强可能有益于延缓糖尿病肾病进展。Objective To investigate the expression of autophagy in glomerular cells of rats with diabetic nephropathy, observe the effects of insulin on the autophagy of podocytes in rats with diabetic nephropathy, and clarify the role of autophagy in the pathogenesis of diabetic nephropathy. Methods Fifty healthy male Wistar rats were adaptively fed for 1 week and randomly divided into two groups. There were 10 rats in the control group A. In the remaining 40 rats, diabetes mellitus models were established by intraperitoneal injection of streptozotocin. After induction of DM, the 40 rats were divided into group B （n = 20） given citrate buffer solution, and group C （n = 20） given subcutaneous ＂injection of insulin by 1.5 U/kg 24 h for 4 weeks. After 4 weeks, we collected the urine and blood samples for determination of urea nitrogen, creatinine, and blood glucose. We observed the pathological changes by PAS stain of the kidney tissues, the changes of podocyte processes by transmission electron＇mi croscope （TEM）, and the LC3Ⅰ/Ⅱ expression was analyzed by Western blotting. Results As compared with group A, the urinary albumin and blood glucose in groups B and C were increased significantly （P〈0. 01）, the glomerular basement membrane （GBM） thickened, mesangial region widened, the matrix increased, the podocyte processes widened and fused, and LC3-Ⅱ/LC3-Ⅰ reduced significantly （P〈0. 01）. As compared with group B, pathological changes in group C were alleviated, and the LC3-Ⅱ/LC3-Ⅰ expression was up-regulated （P〈0. 0Ⅱ）. Conclusions Autophagy is hampered within the kidney of diabetic rats. Insulin can alleviate the pathological changes of glomerulus cells and the damage to podocytes, which might be contributed to the autophagy of podocytes. To maintain a balanced podocyte autophagy could be an effective measure in slowing the progression of diabetic nephropathy.

关 键 词：自噬 足细胞 糖尿病肾病 胰岛素 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]