西南医科大学学报2024，Vol.47Issue(6)：512-521,10.DOI:10.3969/j.issn.2096-3351.2024.06.010
丁酸钠通过调控TGF-β1/SGK1信号通路改善UUO大鼠肾间质纤维化
Sodium butyrate ameliorates renal interstitial fibrosis in UUO rats by regulating the TGF-β1/SGK1 signaling pathway
摘要
Abstract
Objective To investigate the effect of sodium butyrate on renal interstitial fibrosis induced by unilateral ureteral ob-struction(UUO)and its mechanism.Methods The rats were randomly divided into four groups:the sham operation group,the UUO group,the UUO+sodium butyrate low-dose group(1 g·kg-1·d-1),and the UUO+sodium butyrate high-dose group(2 g·kg-1·d-1),with 10 rats in each group.On the 7th and 14th postoperative days,5 rats in each group were randomly selected for execution,and the renal tissue morphology was observed by HE staining,and the interstitial fibrosis was observed by Masson staining.The level of expression of alpha-smooth muscle actin(α-SMA),collagen I(Col-I),tumour necrosis factor alpha(TNF-α),interleukin 6(IL-6),transforming growth factor-β1(TGF-β1),serum/glucocorticoid regulated kinase 1(SGK1),p65,and connective tissue growth factor(CTGF)were detected by immunohistochemistry and RT-PCR.Results Compared with the sham group,HE staining showed pathological changes such as dilated renal tubules and inflammatory cell infiltration in the UUO group.Masson staining showed a significant increase in blue collagen deposition and aggravation of renal lesions with time in the UUO group.But intervention with sodium butyrate reduced renal damage,pathological changes and the degree of interstitial fibrosis.The improvement was significant in the UUO+sodium butyrate high-dose group compared to the UUO+sodium butyrate low-dose group.In addition,the expression levels of proteins and mRNAs of α-SMA,Col-I,TNF-α,and IL-6 in the renal tissues of rats in the UUO group were significantly higher than those in the sham group(P＜0.05),whereas sodium butyrate intervention reduced the protein and mRNA expression of α-SMA,Col-I,TNF-α,and IL-6 in the UUO model,and the UUO+sodium butyrate high-dose group decreased significantly compared with the UUO+sodium butyrate low-dose group.Meanwhile,compared to the sham-operated group,the expression levels of proteins and mRNAs of TGF-β1,SGK1,and their downstream targets p65 and CTGF were significantly up-regulated in UUO rats(P＜0.05),while the changes of TGF-β1/SGK1 signaling pathway in UUO model could be improved after sodium butyrate intervention,and the improvement was more obvious in the UUO+sodium butyrate high-dose group.Conclusion Sodium butyrate may significantly ameliorate renal interstitial fibrosis in UUO rats by reducing inflammation and modulating the TGF-β1/SGK1 signaling pathway.关键词
丁酸钠/单侧输尿管梗阻/肾间质纤维化/炎症/TGF-β1/SGK1信号通路Key words
Sodium butyrate/Unilateral ureteral obstruction model/Renal interstitial fibrosis/Inflammation/TGF-β1/SGK1 sig-naling pathway分类
医药卫生引用本文复制引用
黄越熙,丁文飞,刘江,陈镜伊,吴蔚桦,康婷,欧三桃..丁酸钠通过调控TGF-β1/SGK1信号通路改善UUO大鼠肾间质纤维化[J].西南医科大学学报,2024,47(6):512-521,10.基金项目
四川省自然科学基金(2023NSFSC1530) （2023NSFSC1530）
