济肾胶囊调节细胞因子治疗ADR肾病大鼠作用机制的研究

Mechanism of Jishen Capsule in Reatment of ADR Nephropathy by Regulating Cytokines in Rats

目的:观察济肾胶囊通过调节细胞因子对ADR肾病模型大鼠的治疗作用,并探讨其作用机制。方法:采用阿霉素2次尾静脉注射法建立ADR肾病大鼠模型并随机分为模型组,阳性药黄葵胶囊组(1.88 g·kg-1),济肾胶囊高、中、低剂量组(2.25,1.13,0.56 g·kg-1),正常组,每组10大鼠。7 d后开始给药,并于7,14,28 d,检测各组大鼠24 h尿蛋白定量;检测血液生化指标总蛋白(TP),甘油三酯(TG),总胆固醇(TC),白蛋白(Alb),尿素氮(BUN),血肌酐(SCr);采用ELISA法检测血清中细胞因子肿瘤坏死因子α(TNF-α),白细胞介素-8(IL-8),核因子-κB(NF-κB),转化生长因子-β1(TGF-β1);测定血清超氧化物岐化酶(SOD),丙二醛(MDA)及HE染色观察肾组织病理变化。结果:与正常组比较,模型组24 h蛋白尿,血清中TG,TC,SCr,BUN的含量及细胞因子TNF-α,IL-8,NF-κB,TGF-β1,MDA的水平明显升高(P<0.01),TP,Alb的含量及血清SOD活性明显降低(P<0.01);济肾胶囊高剂量组能显著降低模型大鼠24 h蛋白尿;可明显降低血清中TG,TC,SCr,BUN的含量(P<0.05,P<0.01),显著提高TP,Alb的含量(P<0.05,P<0.01);可明显的降低细胞因子TNF-α,IL-8,NF-κB,TGF-β1的水平(P<0.05,P<0.01),能提高血清SOD活性,降低血清MDA含量(P<0.05),减轻肾脏组织的病变程度,改善肾功能。结论:济肾胶囊通过调节细胞因子TNF-α,IL-8,NF-κB,TGF-β1治疗ADR肾病模型大鼠,并对肾组织具有的保护作用。

Objective： To observe the therapeutic effect of Jishen capsule in models of ADR nephropathy rats by regulating cytokines,and explore the mechanism of action. Method： The models of ADR rats were established by twice intravenous injection of adriamycin and randomized into model group,positive ambrette capsule group（ 1. 88 g·kg- 1）,Jishen capsule high,medium and low dose groups（ 2. 25,1. 13,0. 56 g·kg- 1）,and a normal group. 10 rats was included in each group. Seven days later,drug administration was started. 24 hour urine protein quantity was examined in each group on day 7,14,and 28. Blood biochemical indicators of total protein（ TP）,triglyceride（ TG）,total cholesterol（ TC）,albumin（ Alb）,serum creatinine（ SCr）,and urea nitrogen（ BUN） were detected. Serum tumor necrosis factor-α（ TNF-α）,interleukin-8（ IL-8）,nuclear factor-κB（ NF-κB）,transforming growth factor-β1（ TGF-β1） were measured by ELISA. Activity of superoxide dismutase（ SOD）,malonaldehyde（ MDA） were detected in the serum and renal pathological changes were observed by HE staining. Result： Compared with the normal group,24 h proteinuria,TG,TC,SCr,BUN contents in serum and levels of TNF-α,IL-8,NF-κB,TGF-β1,MDA were significantly increased,while TP,Alb contents and serum SOD activity were significantly reduced in model group（ P〈0. 01）. Jishen capsule high-dose group could significantly reduce 24 h proteinuria of the ADR nephropathy rats,decrease the contents of TG,TC,SCr,BUN（ P〈0. 05,P〈0. 01） and significantly increase the level of TP,Alb in serum（ P〈0. 05,P〈0. 01）,significantly reduce the cytokines level of TNF-α,IL-8,NF-κB,TGF-β1in serum（ P〈0. 05,P〈0. 01）,increase the activity of serum SOD and decrease serum MDA level（ P〈0. 05）,relieve the pathological changes of renal tissues and improve renal function. Conclusion： Jishen capsules can treat the rats with ADR nephropathy by regulating cytokines levels of TNF-α,IL-8,NF-κB,and TGF-β1in serum,with protective effects on renal tissues.