4-PBA治疗单侧肾输尿管结扎小鼠肾脏纤维化的机制探讨  

Investigation on the mechanisms of 4-phenylbutyric acid in renal interstitial fibrosis in mice with unilateral ureteral obstruction

作　　者：余剑 陈曦[1] 方洁[1] 徐爱萍 邵德翠[1] YU Jian;CHEN Xi;FANG Jie;XU Aiping;SHAO Decui(Laboratory of Cell Electrophysiology,Wannan Medical College,Wuhu 241002,Anhui,China)

机构地区：[1]皖南医学院细胞电生理研究室,安徽芜湖241002

出　　处：《皖南医学院学报》2022年第2期113-116,共4页Journal of Wannan Medical College

基　　金：安徽高校自然科学研究项目(KJ2019A0408)。

摘　　要：目的:观察4-苯基丁酸(4-PBA)对肾纤维化的疗效与机制。方法:雄性C57BL/6J小鼠行单侧输尿管梗阻(UUO)手术后分成2组(UUO组与4-PBA组),4-PBA组给予4-PBA(300 mg/kg)灌胃。大鼠肾小管上皮细胞(NRK-52E)给予4-PBA和TGF-β处理。Western blot检测Fibronectin、p47phox、CollagenⅣ和GRP78蛋白的表达量。结果:天狼星红染色结果显示,4-PBA减轻UUO模型小鼠的胶原沉积,Western blot显示,相较于UUO组,4-PBA治疗组肾皮质Fibronectin、CollagenⅣ和GRP78蛋白表达降低(P<0.05)。在NRK-52E细胞,TGF-β剂量依赖性增加Fibronectin和GRP78蛋白表达量,4-PBA(2 mmol/L)减轻TGF-β(10 ng/mL)诱导的Fibronectin、p47phox、CollagenⅣ和GRP78蛋白高表达(P<0.05)。结论:4-PBA可通过减轻内质网应激和氧化应激来治疗肾纤维化。Objective:To investigate the efficacy and underlying mechanisms of 4-phenylbutyric acid(4-PBA)in management of renal fibrosis mouse models.Methods:Male C57BL/6J mice were initially undergone unilateral ureteral obstruction(UUO),and then randomly divided into 4-PBA group and UUO group.Mice in the experimental group were given 4-PBA(300 mg/kg)by gavage.Rat renal tubular epithelial NRK-52E cells were treated with 4-PBA and transforming growth factor(TGF-β).Western blot assay was used to measure the protein expression of fibronectin,collagen IV,glucose-regulated protein 78(GRP78),and p47phox.Results:Sirius red staining showed that the 4-PBA treatment reduced collagen deposition in the mouse models with unilateral ureteral obstruction(UUO),Western blot revealed that the level of fibronectin,collagen IV and GRP78 was lower in mice treated by 4-PBA than that of UUO group(P<0.05).TGF-βincreased fibronectin and GRP78 level in NRK-52E cells in a dose-dependent fashion.Treating with 4-PBA(2 mmol/L)attenuated TGF-βinduced fibronectin,p47phox,collagen IV and GRP78 protein expression in the cells(P<0.05).Conclusion:4-PBA may be a therapeutic strategy for treating renal fibrosis via selectively attenuating endoplasmic reticulum stress and oxidative stress.

关 键 词：内质网应激 4-苯基丁酸 氧化应激 肾纤维化 单侧输尿管梗阻 

分 类 号：R692[医药卫生—泌尿科学] R965[医药卫生—外科学]