左归丸对肾病综合征模型大鼠NF-κB和TNF-α表达的影响

Effects of Zuogui pill on the expression of NF-κB and TNF-α in rats with nephrotic syndrome

目的研究左归丸对阿霉素大鼠肾病综合征模型的治疗作用。方法将85只SPF级雄性Wistar大鼠随机分为空白对照组、模型对照组、左归丸低剂量组(1.62 g/kg)、左归丸中剂量组(3.24 g/kg)、左归丸高剂量组(6.48 g/kg)、醋酸泼尼松组(0.9 mg/kg)。除空白对照组外,其余各组分别尾静脉注射阿霉素6.5 mg/kg。连续灌胃给药治疗12周。实验结束时收集24 h尿液,检测尿蛋白。末次给药1 h后,乙醚麻醉大鼠,腹主动脉取血,检测各组大鼠血清总三酰甘油(TG)、总胆固醇(TC)、尿素氮(BUN)、血肌酐(Scr)。采血后取肾脏,置于4%多聚甲酸溶液中固定24 h。采用HE染色检查肾脏病理变化,采用免疫组化技术检测各组大鼠肾脏NF-κB p65及肿瘤坏死因子TNF-α的表达水平。结果与模型对照组相比,左归丸低剂量组、中剂量组、高剂量组和醋酸泼尼松组24 h尿蛋白显著降低(P<0.01)。与模型对照组相比,醋酸泼尼松组血清尿素氮显著降低(P<0.05)。与模型对照组相比,左归丸中剂量组、高剂量组和醋酸泼尼松组血肌酐显著降低(P<0.05或P<0.01)。与模型组相比,左归丸各治疗剂量组和醋酸泼尼松组的肾组织病变明显减轻,HE染色均匀,肾间炎性细胞浸润减轻,基膜和系膜增生较模型对照组缓解。与模型对照组相比,左归丸高剂量组和醋酸泼尼松组NF-κB P65表达显著降低(P<0.05)。与模型对照组相比,左归丸低剂量组、中剂量组、高剂量组和醋酸泼尼松组TNF-α表达显著降低。结论左归丸对阿霉素引起的大鼠肾病综合征模型具有治疗作用,该作用可能与其对NF-κB信号通路的调节有关。

Objective To study the therapeutic effect of Zuogui pill on adriamycin-induced nephrotic syndrome in rats.Methods Totally 85 SPF male Wistar rats were randomly divided into blank control group,model control group,Zuogui pill low-dose group(1.62 g/kg),Zuogui pill medium-dose group(3.24 g/kg),Zuogui pill high-dose group(6.48 g/kg)and prednisone acetate group(0.9 mg/kg).Except for the blank control group,the other groups were injected with adriamycin 6.5 mg/kg in the tail vein.Treatment was given by continuous intragastric administration for 12 weeks.Urine for 24 hours was collected at the end of the experiment and urine protein was measured.The rats were anesthetized with ether,and blood was taken from the abdominal aorta at 1 h after the last administration.The serum total triglyceride(TG),total cholesterol(TC),urea nitrogen(BUN),and serum creatinine(Scr)in each group were detected.The kidneys were taken and fixed in a 4%paraformic acid solution for 24 h.The pathological changes of the kidneys were examined by HE staining,and the expression levels of NF-κB p65 and tumor necrosis factor TNF-αin the kidneys of each group were detected by immunohistochemical techniques.Results Compared with model control group,the 24 h urinary protein in Zuogui pill groups and prednisone acetate group was significantly decreased(P<0.01);the serum urea nitrogen in prednisone acetate group was significantly decreased(P<0.05);the blood creatinine of Zuogui pill medium-and high-dose group and prednisone acetate group were significantly decreased(P<0.05 or P<0.01).Compared with model group,the renal tissue lesions of Zuogui Pill treatment groups and prednisone acetate group were improved,HE staining was uniform,and the inter-renal inflammatory cell infiltration was reduced.The basement membrane and mesangial proliferation were alleviated compared with model control group.The expression of NF-κB P65 in Zuogui pill high-dose group and prednisone acetate group was lower than that that in model control group(P<0.05);the expression of TNF-αin Zuogui pill groups and prednisone acetate group was lower than that in model control group(P<0.05).Conclusion Zuogui pill has a therapeutic effect on adriamycin-induced nephrotic syndrome in rat models,which may be related to its regulation of NF-κB signaling pathway.