【摘要】 为探究济生肾气丸对小鼠肾间质纤维化的影响及作用机制，本试验将小鼠随机分为对照组、纤维化模型（UUO）组、阳性药物厄贝沙坦组[10 mg/（kg·bw·d）]、济生肾气丸组[1.17 g/（kg·bw·d）]。造模成功后，各组小鼠灌胃给予相应药物14 d后，检测小鼠血清尿素氮（BUN）和血清肌酐（Scr）水平的变化，通过苏木精-伊红（H. E.）染色、Masson三色染色观察小鼠肾脏病理形态学变化和肾间质纤维化程度，Western blot检测肾脏纤维化和Hippo信号通路相关蛋白表达水平。结果显示，给药14 d后，与UUO组相比，济生肾气丸组小鼠BUN水平无显著变化（P> 0.05）,Scr水平显著降低（P <0.05）。与UUO组比较，济生肾气丸组和厄贝沙坦组小鼠肾小球面积明显减小、系膜增生明显减少，肾小球和肾间质纤维化明显减轻，α-平滑肌肌动蛋白（α-SMA）、哺乳动物ste20样激酶1/2 (MST1/2)、Yes关联蛋白及具有PDZ结合基序的转录共激活因子蛋白表达水平均极显著降低（P <0.01）。结果表明，济生肾气丸可以抑制小鼠肾间质纤维化进展，维持小鼠肾功能，其作用机制可能与抑制Hippo信号通路有关。本试验揭示了济生肾气丸通过调控Hippo信号通路改善肾间质纤维化的分子机制，为中药复方靶向干预器官纤维化提供了理论依据。更多还原

【Abstract】 To investigate the effect and underlying mechanism of Jisheng Shenqi Pill on renal interstitial fibrosis in mice, the animals were randomly divided into four groups: Control group, Fibrosis model(UUO) group, Irbesartan group [positive control, 10 mg/（kg·bw·d）, and Jisheng Shenqi Pill group [1. 17 g/（kg·bw·d）]. After successful establishment of the model, mice were administrated the corresponding drugs by gavage for 14 days. Serum blood urea nitrogen(BUN) and creatinine(Scr) levels were measured. Renal pathological changes and degree of interstitial fibrosis were observed using hematoxylin and eosin(H. E.) staining and Masson′s trichrome staining. The expression levels of fibrosis-related proteins and Hippo signaling pathway proteins were evaluated by Western blot. The results showed that after 14 days of treatment, compared with the UUO group, BUN levels in the Jisheng Shenqi Pill group showed no significant difference(P > 0. 05), while Scr levels were significantly decreased(P < 0. 05).Compared with the UUO group, both the Jisheng Shenqi Pill and Irbesartan groups exhibited significantly reduced glomerular area and mesangial proliferation, with marked alleviation of glomerular and interstitial fibrosis. Expression levels of α-smooth muscle actin(α-SMA), mammalian ste20-like kinase 1/2(MST1/2), and Yes-associated protein/transcriptional co-activator with PDZbinding motif(YAP/TAZ) proteins were extremely significant downregulated(P < 0. 01). These findings indicate that Jisheng Shenqi Pill can inhibit the progression of renal interstitial fibrosis in mice and maintain renal function, possibly by inhibiting the Hippo signaling pathway. This study elucidates the molecular mechanism by which Jisheng Shenqi Pill ameliorates renal fibrosis via Hippo pathway regulation, providing a theoretical basis for traditional Chinese medicine compound-based anti-fibrotic therapy.更多还原