扶正化瘀方抗大鼠肾间质纤维化的作用

Effects of Fuzheng Huayu Recipe in Antagonizing Rat's Renal Interstitial Fibrosis

目的观察扶正化瘀方抗氯化汞(HgCl_2)诱导的大鼠肾间质纤维化病变的作用,并初步探讨其作用机制。方法将大鼠随机分为正常组、模型组、扶正化瘀方(FZHY)组及维生素E(VitE)组,模型组用HgCl_2 8 mg/kg灌胃9周,FZHY组(4.6 g/kg)和VitE组(100 mg/kg)分别给予相应的药物干预。检测肾功能情况(Cr和BUN),盐酸水解法检测肾组织羟脯氨酸(Hyp)含量,HE染色、Masson染色和六胺银(PASM)染色观察肾组织病理形态,Western blot观察Ⅰ型胶原(ColⅠ)、纤维连接蛋白(FN)、α-平滑肌肌动蛋白(α-SMA)的表达。结果与模型组比较,FZHY组及VitE组大鼠肾体比(双肾质量/体重)明显下降(P<0.05)、肾组织Hyp含量明显下降(P<0.05),血清Cr和BUN含量明显下降(P<0.01),肾脏纤维化程度明显减轻。其中FZHY组比VitE组轻。FZHY组和VitE组肾组织ColⅠ和FN表达均较模型组减弱(ColⅠ,P<0.05;FN,P<0.01)。FZHY组α-SMA表达较模型组减弱(P<0.01),VitE组则无明显变化(P>0.05)。结论FZHY可改善HgCl_2诱导模型大鼠的肾功能损伤,减少细胞外基质沉积,减轻肾间质纤维化病变,其作用机制与抑制肌成纤维细胞活化有关。

Objective To observe the effects of Fuzheng Huayu Recipe （FHR） on rat＇s renal interstitial fibrosis induced by mercuric chloride （ HgCl2 ）, and to explore preliminarily its mechanism of action. Methods Rats were randomly divided into four groups： the normal group, the model group, the FHR group and the vitamine E group, the latter two were treated respectively by FHR 4.6 g/kg and vitamine E 100 mg/kg. Rats model was established by oral administration of 8 mg/kg HgCl2 for 9 weeks. Serum creatinine （Cr） and urea nitrogen （BUN） content were tested with corresponding test kits; hydroxyproline （Hyp） content in kidney was assayed with hydrochloric acid hydrolysis; renal histologic change was observed with HE, Masson and methenamine silver （PASM） staining; and collagen type Ⅰ （Col Ⅰ）, as well as protein expressions of fibronectin （FN） and asmooth muscle actin （α-SMA） was determined with Western blot. Results Compared with the model group, the kidney/body weight ratio, serum levels of Cr and BUN, kidney Hyp content, and severity of renal interstitial fibrosis in the two treated groups were significantly lower （ P 〈0.05 or P 〈0.01 ）, and the improvements were more significant in the FHR group than those in the vitamine E group; Coll and FN protein expression was also weaker in the two treated group （Col, P〈0.05; FN, P〈0.01 ） ; while the expression of a-SMA was lower in the FHR group （P〈0.01）, but it wasn＇t in the vitamine E group （P〉0.05）. Conclusion FHR could improve the HgCl2- induced renal function injury in rats, decrease extracellular matrix dEposition and restrain renal interstitial fibrosis, the mechanism of action might be related with its inhibitory effect on myofibroblast activation.