吕树泉 路菲菲 苏秀海 王元松

摘要 目的：比較三黄益肾胶囊与雷米普利胶囊对糖尿病肾病（DN）的干预作用，探析肾脏保护深层机制，为临床防治DN提供实验依据。方法：选用雄性SD大鼠，按随机数字表法分为空白对照组、模型对照组、雷米普利组、三黄益肾胶囊低剂量（0.4 g/kg）组、三黄益肾胶囊中剂量（0.8 g/kg）组、三黄益肾胶囊高剂量（1.6 g/kg）组6组，每组10只。给药治疗8周后，检测各组大鼠肌酐（SCr）、尿素氮（BUN）、三酰甘油（TG）、总胆固醇（TC）及24 h尿微量白蛋白等指标。光镜下观察肾脏形态学变化。免疫组化观察肾病蛋白（nephrin）、单核细胞超化蛋白-1（MCP-1）、胰岛素样生长因子（IGF-1）蛋白表达，RT-PCR观察nephrin mRNA、MCP-1mRNA及IGF-1mRNA表达水平。结果：造模后大鼠TG、TC、SCr、BUN、24 h尿微量白蛋白、MCP-1及IGF-1mRNA水平均明显升高（P<0.05），nephrinmRNA表达明显降低（P<0.05）;与模型对照组比较，三黄益肾胶囊组TG、TC、SCr、BUN、24 h尿微量白蛋白、MCP-1及IGF-1 mRNA水平均明显下降（P<0.05），nephrinmRNA水平明显上升（P<0.05），并能改善大鼠肾组织病变。结论：三黄益肾胶囊可能通过下调IGF-1、MCP-1mRNA表达，上调nephrinmRNA表达，改善肾组织病变并起保护作用。

关键词 三黄益肾胶囊;糖尿病肾病;基因;蛋白;肾脏保护

Experimental Study on the Prevention and Treatment of Diabetic Nephropathy of Rats with Sanhuang Yishen Capsules

LYU Shuquan1，LU Feifei2，SU Xiuhai1，WANG Yuansong1

（1 Department of Endocrinology，Cangzhou Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Hebei University of Traditional Chinese Medicine，Cangzhou 061001，China; 2 Graduate School of Hebei University of Traditional Chinese Medicine，Shijiazhuang 050200，China）

Abstract Objective：To compare the intervention effects of Sanhuang Yishen Capsules and Ramipril Capsule on rats with diabetic nephropathy，and to analyze the deep mechanism of renal protection，and to provide reliable experimental basis for clinical prevention and treatment of diabetic nephropathy.Methods：Male SD rats were selected and used and they were divided into 6 groups according to the random number table，namely a blank control group，a model control group，a ramipril group and the a Sanhuang Yishen Capsules low，medium and high doses（0.4，0.8，1.6）g/kg groups，with 10 rats in each group.After 8 weeks of drug administration，the indexes of creatinine，urea，triglyceride，total cholesterol and 24 h urinary protein were measured in each group.The morphological changes of the kidneys were observed under light microscope.The expression of nephrin，MCP-1 and IGF-1 protein expression were observed by immunohistochemistry.The expression of nephrin mRNA，MCP-1 mRNA and IGF-1 mRNA were observed by RT-PCR.Results：After modeling，the levels of triglyceride，total cholesterol，creatinineQ，urea，24-hour urinary microalbumin，MCP-1 and IGF-1 mRNA were significantly increased（P<0.05），and the expression of nephrin mRNA was significantly decreased（P<0.05）.Compared with the model control group，the levels of triglyceride，total cholesterol，creatinine，urea，24 h urinary microalbumin，MCP-1，and IGF-1 mRNA were significantly decreased in Sanhuang Yishen Capsules group（P<0.05），nephrin mRNA levels weresignificantly increased（P<0.05），and can improve renal tissue lesions in rats.Conclusion：Sanhuang Yishen Capsules may down-regulate the expression of IGF-1 and MCP-1 mRNA，up-regulate the expression of nephrin mRNA，improve the pathological changes of renal tissue and play a protective role.

Keywords Sanhuang Yishen Capsules; Diabetic nephropathy; Gene; Protein; Kidney protection

中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.03.014

糖尿病肾病（Diabetic Nephropathy，DN）是一种以持续性蛋白尿为特征的临床综合征，表现为肾小球滤过率进行性下降，血压升高，心血管发病率和死亡率增加，为糖尿病患微血管严重并发症之一[1]。据统计，20%～40%的1型糖尿病与2型糖尿病会发展为DN[2]，更以42.8%的高比例成为终末期肾病（ESRD）首要病因[3]。DN发病机制虽然研究较多但仍阐释不明，涉及遗传因素、糖脂代谢紊乱、炎性递质、细胞因子、生长因子等诸多方面，是综合作用的结果。单核细胞超化蛋白-1（MCP-1）、胰岛素样生长因子（IGF）等在DN发生、发展中的作用尚不明确。现代医学推崇以对症治疗为主，饮食调摄等为辅，严格限制蛋白摄入，控制血糖、血压，纠正脂代谢紊乱，进而改善肾脏微循环，但多治标不治本，同时ACEI类药物易引起干咳、升高血钾等，疗效不稳且不良反应大。……