| 摘要: |
| 目的 观察通络方剂对糖尿病大鼠肾小球足细胞的保护作用，探讨糖尿病肾病足细胞损伤的可能机制。 方法 通过腹腔注射链脲佐菌素(60 mg/kg)制作糖尿病大鼠模型，将成模大鼠随机分为糖尿病组(DM组，12只)、糖尿病TLR干预组(DM+TLR组，12只)，另设正常对照组(CON组，8只)。DM+TLR组大鼠予以TLR[0.4 g/(kg·d)]灌胃，DM组和CON组每日均在同一时间予同体积蒸馏水一次性灌胃。干预12周后测定各组大鼠24 h尿蛋白定量；取大鼠肾皮质，采用电子显微镜观察肾小球足细胞超微结构；采用体视学方法 计数足细胞、计算足细胞相对密度；采用蛋白质印迹分析法检测足细胞nephrin蛋白的表达；测定血浆和肾皮质中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和脂质过氧化产物丙二醛(MDA)含量。结果 与CON组比较，DM组和DM+TLR组大鼠肾质量/体质量比值、血糖和24 h尿蛋白升高(P均＜0.01);12周时DM组大鼠肾小球基底膜增厚、足细胞足突融合、微绒毛化，足细胞计数减少(P＜0.01)、足细胞相对密度降低(P＜0.01)且nephrin表达减少(P＜0.01)。DM+TLR组足突形态接近正常，基底膜增厚,但较DM组减轻，足细胞计数、足细胞相对密度和nephrin表达量均高于DM组(P均＜0.01)。与CON组比较，DM组和DM+TLR组大鼠在观察终点血浆和肾皮质SOD、GSH-Px活性均降低(P＜0.01，P＜0.05)，MDA含量则升高(P＜0.01，P＜0.05)；与DM组相比较，DM+TLR组血浆和肾皮质SOD、GSH-Px活性增加(P均＜0.01)，MDA含量降低(P＜0.01，P＜0.05)。结论TLR可以改善糖尿病大鼠肾小球的足细胞损伤，可能与其抗氧化应激作用有关。 |
| 关键词: 糖尿病肾病 通络方剂 足细胞 氧化应激 nephrin |
| DOI：10.3724/SP.J.1008.2011.0955 |
| 投稿时间：2011-07-17修订日期：2011-08-30 |
| 基金项目:国家重点基础研究发展计划(“973”计划，2005CB523304). |
|
| Effects of Tongluo recipe on injury of glomerular visceral epithelial cells in streptozotocin-induced diabetic rats |
| SUN Liang-liang1,LI Wen-tong2,WANG Hua3,ZOU Jun-jie1,SHI Yong-quan1,LIU Zhi-min1* |
(1. Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
2. The First Sanatorium for Retired Cadre, Garrison Command of Shanghai, Shanghai 200040, China
3. Department of Cardiology, Wuhan General Hospital, PLA Guangzhou Military Area Command, Wuhan 430070, Hubei, China
*Corresponding author.) |
| Abstract: |
| ObjectiveTo investigate the therapeutic effects and the possible mechanisms of Tongluo recipe(TLR)on podocyte injury in streptozotocin-induced diabetic rats. MethodsDiabetes was induced by a single intraperitoneal injection of streptozotocin(60 mg/kg) dissolved in citrate buffer. The diabetic model rats were randomly divided into two groups(n=12): diabetic mellitus(DM) group and DM+TLR group. Rats in the DM+TLR group received 0.4 g/(kg·d) TLR throughout the experiment. Rats in the DM group and CON group (n=8) were given celiac perfusion of distilled water once at the same time and dose. After 12-week treatment, 24 h urinary protein of rats was determined; the cellular ultrastructures of podocytes were observed by transmission electronic microscope; the number and the density of podocytes in glomerulis were measured by stereological dissector/fractionator methods; the expression of nephrin in renal cortical tissue was detected by Western blotting analysis; the activity of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) and the content of malondialdehyde(MDA) were measured in the plasma and renal cortical tissue. ResultsCompared with CON group, DM group and DM+TLR group had significantly increased ratio of kidney mass to body mass, blood glucose, and 24-h proteinuria(all P＜0.01); at the 12th week, the glomerular basement membrane in DM group became conspicuously thick, foot process fusion and microvilli of podocytes were observed, and nephrin expression, podocyte number and podocyte density in the glomerulis were all significantly decreased（P＜0.01）. The morphology of the foot process was almost normal in DM+TLR group, with the basement membrane thickened, but was slighter than that in the DM group; and nephrin expression, podocyte number and podocyte density in DM+TLR group were significantly higher than those in the DM group（P＜0.01）. Compared with CON group, DM group and DM+TLR group had significantly increased MDA content, and significantly decreased SOD and GSH-Px activities in the plasma and renal cortical tissue（P＜0.01, P＜0.05）. Compared with DM group, DM+TLR group had significantly increased SOD and GSH-Px activities and significantly decreased MDA content in plasma and renal cortical tissue（P＜0.01, P＜0.05）. ConclusionTLR can ameliorate podocyte injury probably through depleting free radical production and increasing activities of antioxidatant. |
| Key words: diabetic nephropathies Tongluo recipe podocyte oxidative stress nephrin |
