王丽华刘丽秋杨鹏鹏王福荣于俊生郑　燕李平海李淑秀

（1.青岛大学附属海慈医院，山东　青岛266003；2.青岛大学附属医院，山东　青岛266000；3.中国人民解放军91286部队门诊部，山东　青岛266000）

祛痰通络汤对糖尿病肾病大鼠肾组织内质网应激的影响*

王丽华1刘丽秋2△杨鹏鹏2王福荣1于俊生1郑燕1李平海3李淑秀1

（1.青岛大学附属海慈医院，山东青岛266003；2.青岛大学附属医院，山东青岛266000；3.中国人民解放军91286部队门诊部，山东青岛266000）

目的观察祛痰通络汤对糖尿病肾病大鼠肾组织中内质网应激相关蛋白GRP78，Caspase12的影响。方法高糖高脂饲料联合腹腔注射STZ制备糖尿病肾病模型，随机分为正常对照组、模型组、祛痰通络汤组、四苯基丁酸组，干预8周。观察各组24 h尿蛋白定量、肌酐、肾脏病理学变化；免疫组化和Western blot检测肾组织内质网应激相关蛋白GRP78，Caspase-12的表达。结果经过祛痰通络汤治疗后，大鼠体质量上升，24 h尿蛋白定量、糖化血红蛋白、肌酐下降；病理改变减轻；模型组肾组织的GRP78、Caspase12表达明显升高；祛痰通络汤组GRP78、Caspase-12表达明显降低（均P＜0.05）。结论糖尿病肾病大鼠肾脏中内质网应激反应明显增强，祛痰通络汤降低内质网应激，可能是其肾脏保护作用的重要机制。

糖尿病肾病祛痰通络汤内质网应激

【Abstract】Objective：To investigate the effects of Qutan Tongluo Decoction on the expression of endoplasmic reticulum stress-related molecules GRP78 and Caspase12 in renal of diabetic nephropathy rats.M ethods：The diabetic nephropathy ratmodelwas induced by feeding high-glucose high-fat diet in combination with intraperitoneal injection of STZ.Wistar rats were random ly divided into 4 groups：the normal control group，the model group，Qutan Tongluo Decoction group，and 4-phenyl butyric acid treatment（PBA group）.At the end of 8 weeks，24-hour urinary protein excretion，serum creatinine（Scr）and renal pathological changeswere determined；the expression of glucose-regulated protein 78（GRP78）and Caspase-12 were examined by immunohistochemistry and western blotting respectively.Results：Qutan Tongluo Decoction treatment raised bodymass of rats，reduced 24-hour urinary protein excretion，glycosylated hemoglobin，and serum creatinine，and relieved pathological changes. The expressions of GRP78 and Caspase12 proteins in themodel group was significantly higher；The expressions of GRP78 and Caspase12 proteins in Qutan Tongluo Decoction group dropped significantly（P＜0.05）.Conclusion：Endoplasmic reticulum stress is abundantly expressed in the kidneys of diabetic nephropathy rats.Qutan Tongluo Decoction decreases ER stress，whichmay be an importantmechanism in renal protective effects.

【Key words】Diabetic nephropathy；Qutan Tongluo Decoction；Endoplasmic reticulum stress

糖尿病肾病是糖尿病常见的微血管并发症，是导致终末期肾病（ESRD）的重要原因，发展为ESRD的比例高达20%～40%［1］，目前其发病机制尚未完全阐明，缺乏有效的治疗手段。多数人认为肾脏血流动力学改变、血糖、蛋白质及脂肪代谢紊乱是糖尿病肾病的病变基础。……