Renal fibrosis is a common characteristic of chronic kidney disease (CKD), and it can lead to end-stage renal disease. It has been reported that silibinin or lisinopril (MK-521) can inhibit the progression of renal fibrosis. However, the effect of combination of silibinin with MK-521 on renal fibrosis remains unclear. Therefore, this study aimed to explore the combination of silibinin with MK-521 on renal fibrosis in vitro and in vivo. The cell viability of HK-2 was detected by CCK-8. The gene and protein expression in HK-2 cells were detected by qRT-PCR and Western blot, respectively. Moreover, HFD-induced renal fibrosis mouse model was established to investigate the effect of silibinin in combination with MK-521 on renal fibrosis in vivo. The expressions of collagen I, α-SMA, Smad2 and Smad3 in TGF-β-treated HK-2 cells were notably decreased by MK-521, which was further inhibited in the presence of silibinin. In addition, we found that silibinin significantly enhanced anti-fibrotic effect of MK-521 on HFD-induced renal fibrosis mice. These findings demonstrated that silibinin could significantly increase anti-fibrotic effect of MK-521 in vitro and in vivo. Therefore, the combination of silibinin with MK-521 may serve as a potential strategy for the treatment of renal fibrosis.

中文翻译：

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水飞蓟宾通过下调 TGF-β 信号通路增强 MK-521 的抗肾纤维化作用。

肾纤维化是慢性肾病（CKD）的共同特征，可导致终末期肾病。据报道，水飞蓟宾或赖诺普利（MK-521）可以抑制肾纤维化的进展。然而，水飞蓟宾与 MK-521 联合使用对肾纤维化的影响仍不清楚。因此，本研究旨在探索水飞蓟宾与MK-521联合在体外和体内对肾纤维化的影响。CCK-8检测HK-2的细胞活力。qRT-PCR和Western blot分别检测HK-2细胞中基因和蛋白的表达。此外，建立HFD诱导的肾纤维化小鼠模型，研究水飞蓟宾联合MK-521对体内肾纤维化的影响。I型胶原蛋白、α-SMA、MK-521 显着降低了 TGF-β 处理的 HK-2 细胞中的 Smad2 和 Smad3，在水飞蓟宾存在下进一步抑制。此外，我们发现水飞蓟宾显着增强 MK-521 对 HFD 诱导的肾纤维化小鼠的抗纤维化作用。这些发现表明，水飞蓟宾可以显着增加 MK-521 在体外和体内的抗纤维化作用。因此，水飞蓟宾与 MK-521 的组合可作为治疗肾纤维化的潜在策略。