Luo Yan, Jiang Juan, Cheng Junxiong, Xuan Chen, Xiong Yu, Xiong Weijian, Cao Wenfu, Li Ying
Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing 400016, China.
Evid Based Complement Alternat Med. 2022 Aug 5;2022:4398265. doi: 10.1155/2022/4398265. eCollection 2022.
Rhein is the main extract of L., which has been proved to improve the renal function of chronic kidney disease, but its mechanism is not clear. Therefore, this experiment explored the potential pharmacological effect of rhein on renal interstitial fibrosis rats.
This study explores the potential pharmacological action of rhein. In this work, we investigate the potential pharmacological action of rhein in unilateral urethral obstruction (UUO) rats. Thirty Sprague Dawley rats were randomly divided into three groups: sham, UUO, and rhein (rhein-treated UUO rats) groups. The left ureters of the UUO group rats were exposed and bluntly dissected. The rhein group rats were administered an intragastric gavage of rhein (2 mg·kg·d) for 14 d. Kidney function-related indicators were monitored in these rats, while indexes of pathologic aspects were determined histologically. The expression of -SMA, TGF-1, SHH, Gli1, and Snail was quantified using real-time polymerase chain reaction and western blotting. The NRK-49F cells were incubated with and without SHH (100 ng·ml) for 48 hours. The SHH-activated NRK-49F cells were incubated with cyclopamine (CNP, 20 umol L) or rhein (1 ng·ml). The Gli1 and Snail mRNA and protein level were detected.
In the in vivo experiment, the results exhibited that UUO caused renal pathological damages. However, these changes could be significantly reversed by the administration of rhein. Compared with the untreated UUO group, the rhein group showed reduced kidney tubular atrophy and necrosis, interstitial fibrosis, hyperplasia, and abnormal deposition of extracellular matrix. Rhein reduced the RNA and protein expression of SHH, Gli1, and Snail of the UUO rats. In the in vitro experiment, CNP or rhein treatment decreased the expression of Gli1 and Snail on mRNA and protein levels in SHH-induced NRK-49F cells, suggesting that CNP or rhein suppresses SHH-induced NRK-49F activation. Taken together, these results demonstrated that rhein suppresses SHH-Gli1-Snail signal pathway activation, with potential implications for the treatment of renal fibrosis.
Treatment with rhein remarkably ameliorated renal interstitial fibrosis in UUO rats by regulating the SHH-Gli1-Snail signal pathway.
大黄酸是大黄的主要提取物，已被证明可改善慢性肾脏病的肾功能，但其机制尚不清楚。因此，本实验探讨大黄酸对肾间质纤维化大鼠的潜在药理作用。
本研究探讨大黄酸的潜在药理作用。在此工作中，我们研究大黄酸在单侧输尿管梗阻（UUO）大鼠中的潜在药理作用。30只Sprague Dawley大鼠随机分为三组：假手术组、UUO组和大黄酸组（大黄酸处理的UUO大鼠组）。暴露UUO组大鼠的左输尿管并钝性分离。大黄酸组大鼠灌胃给予大黄酸（2mg·kg·d），持续14天。监测这些大鼠的肾功能相关指标，同时通过组织学方法确定病理方面的指标。使用实时聚合酶链反应和蛋白质印迹法对α-SMA、TGF-β1、SHH、Gli1和Snail的表达进行定量。将NRK-49F细胞在有或无SHH（100ng·ml）的情况下孵育48小时。将SHH激活的NRK-49F细胞与环杷明（CNP，20μmol/L）或大黄酸（1ng·ml）一起孵育。检测Gli1和Snail的mRNA和蛋白水平。
在体内实验中，结果显示UUO导致肾脏病理损伤。然而，给予大黄酸可显著逆转这些变化。与未处理的UUO组相比，大黄酸组肾小管萎缩和坏死、间质纤维化、增生及细胞外基质异常沉积减少。大黄酸降低了UUO大鼠SHH、Gli1和Snail的RNA和蛋白表达。在体外实验中，CNP或大黄酸处理降低了SHH诱导的NRK-49F细胞中Gli1和Snail在mRNA和蛋白水平的表达，表明CNP或大黄酸抑制SHH诱导的NRK-49F激活。综上所述，这些结果表明大黄酸抑制SHH-Gli1-Snail信号通路激活，对肾纤维化治疗具有潜在意义。
大黄酸治疗通过调节SHH-Gli1-Snail信号通路显著改善了UUO大鼠的肾间质纤维化。
