糖尿病肾组织TGF-β-Smads信号通路活化及α-SMA上调表达.docVIP

糖尿病肾组织TGF-β/Smads信号通路活化及α-SMA上调表达[摘要] 目的：探讨TGF-β/Smads信号通路在糖尿病小鼠肾组织中的活化及作用，从信号转导角度探讨糖尿病肾病肾纤维化的发病机制。方法：取雄性C57BL/6小鼠36只，随机分为模型组（30只）和对照组（6只）。模型组采用链脲佐菌素[STZ，50 mg/(kgd)]连续5 d腹腔注射诱导糖尿病模型，对照组用枸橼酸缓冲液腹腔注射。血糖超过16.7 mmol/L为糖尿病诊断标准，观察16周，分别在造模后0、4、8、12、16周处死小鼠。用免疫组化方法检测肾组织TGF-β、磷酸化Smad2/3和α-SMA的表达。结果：对照组小鼠肾组织有基础的TGF-β和磷酸化Smad2/3的表达。糖尿病形成后4周，TGF-β和磷酸化Smad2/3表达明显增加，第12周达高峰，第16周表达减少，但仍高于对照组。对照组小鼠肾组织仅血管平滑肌有α-SMA表达，糖尿病形成后4周肾小球系膜区、肾小管-间质α-SMA的表达显著增加，并持续增加到12周，第16周表达下调，但仍高于对照组。糖尿病肾组织TGF-β、磷酸化Smad2/3及α-SMA的表达时相一致且呈明显正相关。结论：糖尿病小鼠肾组织TGF-β/Smads信号通路被高度活化，可能通过诱导α-SMA的上调表达参与糖尿病肾病肾纤维化的过程。 [关键词] 糖尿病肾病；Smad2/3；肾纤维化；TGF-β [中图分类号] R587.1[文献标识码]A [文章编号]1673-7210（2009）05（a）-016-04 Activation of TGF-β/Smads signal pathway and upregulated expression of α-SMA in diabetic kidney tissue in mice ZHU Shenglang, CHEN Jiehui, JIANG Ying, CHEN Lu, LI Jiuhong, CHANG Juping (Department of Nephrology, Nanshan Affiliated Hospital of Guangdong Medical College, the Sixth Hospital of Shenzhen City, Shenzhen 518052, China) [Abstract] Objective: To investigate the activation and effect of TGF-β/Smads signal pathway in diabetic kidney tissue in mice, and explore the pathogenesy of renal fibrosis of diabetic nephropathy in the aspect of signal transduction. Methods: 36 male homozygous C57BL/6 mice were selected and randomly divided into model group (30 mice) and control group (6 mice).Model group received 5 consecutive daily intraperitoneal (ip) injection of Streptozotocin [STZ, 50 mg/(kg?d)], and control group was intraperitoneally injected with citrate buffer. All mice were followed up for 16 weeks. Diabetes mellitus was confirmed by serum glucose level exceeding 16.7 mmol/L. Mice were killed at 0th, 4th, 8th, 12th and 16th week respectively after establishing models. The kidney tissue was used for histological and morphometric studies, and the expression of TGF-β, phosphorylated Smad2/3 and α-SMA were determined by immunohistochemical staining. Results: Fundamental expression of TGF-β and phosph