Yang Fan, Deng Lu, Li JinPeng, Chen MuHu, Liu Ying, Hu YingChun, Zhong Wu
Department of Emergency Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China.
Department of Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China.
Drug Des Devel Ther. 2020 Sep 3;14:3567-3575. doi: 10.2147/DDDT.S245847. eCollection 2020.
Renal fibrosis is a frequently occurring type of chronic kidney disease that can cause end-stage renal disease. It has been verified that emodin or HGF can inhibit the development of renal fibrosis. However, the antifibrotic effect of emodin in combination with HGF remains unclear.
Cell viability was detected with CCK8. Gene and protein expression in HK2 cells was detected by qRT-PCR and Western blot, respectively. Moreover, a unilateral ureteral obstruction-induced mouse model of renal fibrosis was established for investigating the antifibrotic effect of emodin in combination with HGF in vivo.
HGF notably increased the expression of collagen II in TGFβ-treated HK2 cells. In addition, HGF-induced increase in collagen II expression was further enhanced by emodin. In contrast, fibronectin, αSMA and Smad2 expression in TGFβ-stimulated HK2 cells was significantly inhibited by HGF and further decreased by combination treatment (emodin plus HGF). Moreover, we found that combination treatment exhibited better antifibrotic effects compared with emodin or HGF in vivo.
These data demonstrated that emodin plus HGF exhibited better antifibrotic effects compared with emodin or HGF. As such, emodin in combination with HGF may serve as a new possibilty for treatment of renal fibrosis.
肾纤维化是一种常见的慢性肾病类型，可导致终末期肾病。已证实大黄素或肝细胞生长因子（HGF）可抑制肾纤维化的发展。然而，大黄素与HGF联合使用的抗纤维化作用仍不清楚。
用CCK-8检测细胞活力。分别通过qRT-PCR和蛋白质印迹法检测HK2细胞中的基因和蛋白表达。此外，建立单侧输尿管梗阻诱导的肾纤维化小鼠模型，以研究大黄素与HGF联合使用在体内的抗纤维化作用。
HGF显著增加了经转化生长因子β（TGFβ）处理的HK2细胞中Ⅱ型胶原蛋白的表达。此外，大黄素进一步增强了HGF诱导的Ⅱ型胶原蛋白表达增加。相反，HGF显著抑制了TGFβ刺激的HK2细胞中纤连蛋白、α平滑肌肌动蛋白（αSMA）和Smad2的表达，联合治疗（大黄素加HGF）使其进一步降低。此外，我们发现联合治疗在体内表现出比大黄素或HGF更好的抗纤维化作用。
这些数据表明，与大黄素或HGF相比，大黄素加HGF表现出更好的抗纤维化作用。因此，大黄素与HGF联合使用可能为肾纤维化的治疗提供一种新的可能性。
