探讨复方鱼腥草提取物（牛蒡子及鱼腥草的挥发油、水提物、醇提物的混合物）对2 型糖尿病大 鼠肾脏组织中Sirt1/PGC-1α 通路的影响。方法 将SD 大鼠随机分为正常组、模型组、罗格列酮组（0.3 mg·kg-1）、 白藜芦醇组（0.12 g·kg-1）及复方鱼腥草提取物组（4.5 g·kg-1），每组10 只。采用高糖高脂饲料喂养4 周联合小剂 量腹腔注射1% 链脲佐菌素（STZ，30 mg·kg-1）复制2 型糖尿病大鼠模型。检测各组大鼠24 h 尿蛋白、24 h 尿 白蛋白、尿肌酐以及血清肌酐水平，计算肌酐清除率、肾脏指数。采用HE 染色法观察肾脏组织病理形态学变 化；免疫组化法检测肾脏组织中Sirt1 表达水平；Western Blot 法检测大鼠肾皮质中Sirt1、PGC-1α 蛋白表达水 平。结果 与正常组比较，给药4、8 周后，模型组大鼠的24 h 尿蛋白及尿白蛋白水平、肌酐清除率、肾脏指 数均明显升高（P＜0.05）；肾小球体积明显增大，可见肾间质伴有炎性细胞浸润，系膜区可见明显扩张；免疫 组化显示肾脏组织中的Sirt1 表达显著下调（P＜0.01）；肾皮质中Sirt1、PGC-1α 蛋白表达均明显下调（P＜0.05）。 与模型组比较，复方鱼腥草提取物组大鼠的24 h 尿蛋白及尿白蛋白水平、肌酐清除率、肾脏指数均明显降低 （P＜0.05）；肾小球增大、系膜增生与基质聚积均有明显改善；免疫组化显示肾脏组织中的Sirt1 表达显著上调 （P＜0.01）；肾皮质中Sirt1、PGC-1α 蛋白表达均明显上调（P＜0.05，P＜0.01）。结论 复方鱼腥草提取物对 2 型糖尿病大鼠的早期肾脏损伤具有保护作用，其机制可能与上调肾皮质中Sirt1/PGC-1α 通路有关。

To investigate the effect of compound Houttuyniae Herba extract （a mixture of volatile oil， water extract and alcohol extract of Arctii Fructus and Houttuyniae Herba） on Sirt1/PGC-1α pathway in kidney tissue of type 2 diabetic rats. Methods SD rats were randomly divided into normal group， model group， Rosiglitazone group （0.3 mg·kg-1）， Resveratrol group （0.12 g·kg-1） and compound Houttuyniae Herba extract group （4.5 g·kg-1），with 10 rats in each group. The rat model of type 2 diabetes was replicated by high-sugar and high-fat diet for 4 weeks combined with low-dose intraperitoneal injection of 1 % Streptozotocin（STZ，30 mg·kg-1）. The levels of 24-hour urinary protein， 24-hour urinary albumin， urinary creatinine and serum creatinine were detected， and the creatinine clearance rate and kidney index were calculated. The pathological changes of renal tissue were observed by HE staining. The expression level of Sirt1 in renal tissue was detected by immunohistochemistry. The protein expression levels of Sirt1 and PGC-1α in renal cortex of rats were detected by Western Blot. Results Compared with the normal group， the levels of 24-hour urine protein， urinary albumin， creatinine clearance rate and kidney index in the model group were significantly increased after 4 and 8 weeks of administration （P＜0.05） . Glomerular volume was significantly increased， with inflammatory cell infiltration in renal interstitium and obvious expansion in mesangial area. Immunohistochemistry showed that the expression of Sirt1 in renal tissue was significantly down-regulated （P＜0.01） . The protein expressions of Sirt1 and PGC-1α in renal cortex were significantly down-regulated （P＜0.05） . Compared with the model group， the levels of 24-hour urinary protein and urinary albumin，creatinine clearance rate and kidney index in the compound Houttuyniae Herba extract group were significantly decreased （P＜0.05） . Increased glomerular， mesangial proliferation and matrix accumulation were significantly improved. Immunohistochemistry showed that the expression of Sirt1 in renal tissue was significantly up-regulated （P＜0.01） . The protein expressions of Sirt1 and PGC-1α in renal cortex were significantly up-regulated （P＜0.05， P＜0.01） . Conclusion Compound Houttuyniae Herba extract has a protective effect on early renal injury in type 2 diabetic rats，and its mechanism may be related to the up-regulation of Sirt1/PGC-1α pathway in renal cortex

R285.5

上海市进一步加快中医药传承创新发展三年行动计划中医药高层次人才引领计划项目（2021年~2023年） [ZY（2021-2023） -0403]。