桑黄与雷公藤序贯联合治疗对局灶节段肾小球硬化大鼠肾损伤的影响及机制

目的 研究桑黄联合雷公藤多苷对局灶节段肾小球硬化（focal segmental glomerulosclerosis，FSGS）大鼠早期肾功能和肾脏病理损伤的干预作用及机制。方法 采用单侧肾切除联合2次阿霉素尾静脉注射法建立FSGS大鼠模型，用桑黄水煎剂、雷公藤多苷及联合进行干预治疗。检测血肌酐、尿素氮、血脂等水平，Masson染色观察肾组织病理损伤及纤维化程度，RT-PCR技术检测肾皮质Collage IV、Fibronection、MMP9及TIMP-1的表达水平。结果 与正常对照组比较，模型组大鼠肾功能显著降低（P<0.05），24 h尿蛋白、血脂、心肌酶水平等显著增高（P<0.05）。与模型组比较，桑黄、雷公藤多苷以及联合干预均可降低尿蛋白，改善肾功能和血脂代谢，降低心肌酶水平，改善心脏损伤，联合组整体优于单独干预；联合干预或雷公藤多苷干预均可显著降低细胞外基质积聚，并可增高MMP9 mRNA表达，显著降低TIMP-1 mRNA表达水平。结论 桑黄联合雷公藤多苷可有效改善FSGS大鼠肾功能及肾脏病理损伤，有望为FSGS的防治提供新的治疗措施。

Effect and Mechanism of Sequential Combination of Tripterygium Glycosides and Phellinus Linteus on Renal Injury in Focal Segmental Glomerulosclerosis Rats

OBJECTIVE To observe the intervention effect and mechanism of tripterygium glycosides and Phellinus linteus on early renal function and pathological damage in focal segmental glomerulosclerosis(FSGS) rats model. METHODS The FSGS rat model was established through single nephrectomy and repeated injection of doxorubicin. Different interventions were conducted with Phellinus linteus decoction, tripterygium glycosides, and the combination of them. Serum creatine(Scr), urea nitrogen(BUN), and blood fat were analyzed. Masson staining was used to detect the pathological damage and fibrosis degree of kidney tissue. RT-PCR was used to determine the expression of renal cortex Collage IV, Fibronection, MMP9 and TIMP-1. RESULTS Compared with normal control group, the kidney function of the model group was significantly lower(P<0.05), whereas the levels of 24-hour urinary protein, blood fat, and myocardial enzyme were significantly higher(P<0.05). Compared with model group, different interventions could reduce proteinuria, improve renal function and lipid metabolism, reduce the level of myocardial enzymes and improve cardiac injury. Generally, the combined group was superior to the single intervention. Besides, the combined intervention or the tripterygium glycosides group both could significantly reduce the accumulation of extracellular matrix, increase the expression of MMP9 mRNA whereas reduce the expression of TIMP-1 mRNA. CONCLUSION The combination of Phellinus linteus and tripterygium glycosides can effectively improve the renal function and pathological damage of FSGS rats, which is expected to provide new treatment measures for the prevention and treatment of FSGS.