槐杞黄清膏抑制UUO大鼠肾间质纤维化的初步研究

目的:探讨槐杞黄清膏对肾间质纤维化的疗效及其作用机制.方法:Wistar大鼠随机分为5组,每组5只, 分别为假手术组、UUO(unilateral ureteral obstruction)组,1.5 g·kg^-1槐杞黄治疗组,2.25 g·kg^-1槐杞黄治疗组和3.0 g·kg^-1槐杞黄治疗组.于术后第3天开始,每天分别给予治疗组大鼠1.5 g·kg^-1, 2.25 g·kg^-1,3.0 g·kg^-1槐杞黄清膏水溶剂灌胃;于术后第14 d处死大鼠后获取肾脏组织.梗阻侧肾脏组织行HE、Masson染色,观测肾间质病理改变;免疫组化方法检测肾间质肌成纤维细胞堆积程度;Western-Blot方法检测梗阻侧肾组织α-SMA蛋白表达水平.结果:与假手术组相比,UUO模型组大鼠建模后14 d肾间质严重损伤并伴明显纤维化病变,大量肌成纤维细胞在肾间质广泛堆积.2.25 g·kg^-1,3.0 g·kg^-1槐杞黄清膏治疗UUO大鼠后,间质纤维沉积及间质肌成纤维细胞浸润明显减少.Western Blot检测结果显示2.25 g·kg^-1、3.0 g·kg^-1剂量槐杞黄清膏治疗UUO大鼠14 d时,α-SMA蛋白表达下调.结论:在肾间质纤维化早期使用2.25 g·kg^-1、3.0 g·kg^-1槐杞黄可减轻UUO大鼠肾间质肌成纤维细胞堆积从而减轻肾间质纤维化.

Primary study on antifibrosis mechanism of Huaiqihuang in UUO rats

OBJECTIVE To design this experiments to evaluate therapeutic effects of Chinese herbal medicine Huaiqihuang(HQH) on obstructive kidneys and explore the involved mechanism.METHODS Wistar rats were randomly assigned to five groups, 5 rats in each group. Rats in control groups received sham operation and normal saline. Rats in model groups and treatment groups were intragastrically administrated normal saline and different doses of Huaiqihuang (Low-dose 1.5 g·kg^-1, Mid-dose 2.25 g·kg^-1, High-dose 3.0 g·kg^-1) respectively from D3 after left ureter ligation. Protein expressions of ɑ-SMA in obstructive kidneys were analyzed by IHC and western blots. RESULTS After rats were sacrificed on D14, histopathological changes were observed, UUO rats on D14 showed significant tubulointerstitial lesions with severe fibrosis. Clusters of myofibroblasts appeared in renal institium. Mid-dose and High-dose rather than low-dose treated rats showed lesions and fibrosis of mild degrees. The study revealed that both Mid-dose and High-dose significantly decreased accumulation of myofibroblasts in renal institium and reduced ɑ-SMA protein expression. CONCLUSION 2.25 g·kg^-1 and 3.0 g·kg^-1 HQH at early stage of renal fibrosis can effectively attenuate renal interstitial fibrosis by inhibiting accumulation of myofibroblasts.