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[摘要]
目的 研究组分配伍四逆汤对大鼠膜性肾病的治疗作用及机制。方法 将45只雄性SD大鼠,随机分为对照组、模型组和组分配伍四逆汤组,除对照组外,其余各组尾iv兔抗大鼠Fx1A抗血清制备大鼠膜性肾病模型。造模成功后,组分配伍四逆汤组大鼠ig 9.6 g/kg组分配伍四逆汤,模型组和对照组ig等量蒸馏水,连续给药12周。试剂盒法检测大鼠血清中肌酐(Scr)、尿素氮(BUN)以及白蛋白(Alb)含量;取肾脏检测肾指数,苏木素-伊红(HE)染色观察肾组织的病理情况;ELISA法检测肾组织中转化生长因子-β1(TGF-β1)、纤维连接蛋白(FN)以及IV型胶原(Col-IV)含量;采用Western blotting法检测肾脏中ERK1/2和胞浆型磷脂酶(cPLA2)蛋白磷酸化水平。结果 与对照组比较,模型组血清中Scr、BUN水平以及肾指数明显升高(P<0.05、0.01),血清Alb水平明显降低(P<0.01),肾组织中TGF-β1、FN和Col-IV含量以及ERK1/2、cPLA2磷酸化蛋白表达均显著升高(P<0.05、0.01);与模型组比较,组分配伍四逆汤显著降低血清中Scr、BUN水平以及肾指数(P<0.05、0.01),升高血清中Alb水平(P<0.01),降低肾组织中TGF-β1、FN、Col-IV含量,减少肾组织中ERK1/2和cPLA2磷酸化蛋白表达(P<0.05、0.01);HE染色结果显示,组分配伍四逆汤可以改善膜性肾病大鼠肾脏的病理变化。结论 组分配伍四逆汤对膜性肾病大鼠发挥明显治疗作用,其作用机制可能与抑制ERK/cPLA2信号通路激活相关。
[Key word]
[Abstract]
Objective To observe therapeutic effect of Component Compatibility Sini Decoction (CCSD) on membranous nephropathy in rats and its mechanisms. Method Totally 45 SD male rats were randomly divided into control group, model group and CCSD group, rat models were given into antigen Fx1A antiserum by tail iv injection except control group. After the success of model, the rats in CCSD group were ig administered 9.6 g/kg drugs, meanwhile the rats in control and model group were ig administration with the same dose of distilled water for 12 weeks; At the time points of 12 week, the levels of serum creatine (Scr), blood urea nitrogen (BUN) and serum albumin (Alb) were detected by kits. At the end of 12th week, kidney weight index was detected and renal pathological changes was observed by HE staining; The content of transforming growth factor-β1 (TGF-β1), fibronectin(FN), and collagen IV (Col-IV) in renal tissue was detected by ELISA; Western blotting was used to test the protein expression of ERK1/2 and cPLA2 in the kidney. Results Compared with control group, the levels of serum Scr, BUN and kidney weight index were increased significantly (P<0.05 or 0.01), serum Alb was decreased obviously (P<0.05 or 0.01), the content of TGF-β1, FN, Col-IV, and the protein expression of p-ERK1/2 and p-cPLA2 were significantly increased in renal tissue (P<0.05 or 0.01). Compared with model group, CCSD could degrade significantly the levels of serum Scr, BUN, and index of kidney weight decreased (P<0.05 or 0.01), increase the level of serum Alb (P<0.01), and reduce the content of TGF-β1, FN, Col-IV and the protein expression of p-ERK1/2 and p-cPLA2 in renal tissue (P<0.05 or 0.01); HE staining results showed that CCSD could improve renal pathological changes. Conclusion CCSD has certain therapeutic effect for rats with membranous nephropathy, its mechanism may be related to the inhibition of activation of ERK/cPLA2 signaling pathway.
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[基金项目]
国家自然科学基金资助项目(81373546)