目的 研究組分配伍四逆湯對(duì)大鼠膜性腎病的治療作用及機(jī)制。方法 將45只雄性SD大鼠，隨機(jī)分為對(duì)照組、模型組和組分配伍四逆湯組，除對(duì)照組外，其余各組尾iv兔抗大鼠Fx1A抗血清制備大鼠膜性腎病模型。造模成功后，組分配伍四逆湯組大鼠ig 9.6 g/kg組分配伍四逆湯，模型組和對(duì)照組ig等量蒸餾水，連續(xù)給藥12周。試劑盒法檢測(cè)大鼠血清中肌酐（Scr）、尿素氮（BUN）以及白蛋白（Alb）含量；取腎臟檢測(cè)腎指數(shù)，蘇木素-伊紅（HE）染色觀察腎組織的病理情況；ELISA法檢測(cè)腎組織中轉(zhuǎn)化生長(zhǎng)因子-β1（TGF-β1）、纖維連接蛋白（FN）以及IV型膠原（Col-IV）含量；采用Western blotting法檢測(cè)腎臟中ERK1/2和胞漿型磷脂酶（cPLA2）蛋白磷酸化水平。結(jié)果 與對(duì)照組比較，模型組血清中Scr、BUN水平以及腎指數(shù)明顯升高（P<0.05、0.01），血清Alb水平明顯降低（P<0.01），腎組織中TGF-β1、FN和Col-IV含量以及ERK1/2、cPLA2磷酸化蛋白表達(dá)均顯著升高（P<0.05、0.01）；與模型組比較，組分配伍四逆湯顯著降低血清中Scr、BUN水平以及腎指數(shù)（P<0.05、0.01），升高血清中Alb水平（P<0.01），降低腎組織中TGF-β1、FN、Col-IV含量，減少腎組織中ERK1/2和cPLA2磷酸化蛋白表達(dá)（P<0.05、0.01）；HE染色結(jié)果顯示，組分配伍四逆湯可以改善膜性腎病大鼠腎臟的病理變化。結(jié)論 組分配伍四逆湯對(duì)膜性腎病大鼠發(fā)揮明顯治療作用，其作用機(jī)制可能與抑制ERK/cPLA2信號(hào)通路激活相關(guān)。

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.

國(guó)家自然科學(xué)基金資助項(xiàng)目（81373546）