基础医学与临床2025，Vol.45Issue(5)：637-643,7.DOI:10.16352/j.issn.1001-6325.2025.05.0637
人源PCSK9D374Y加重蛋氨酸胆碱缺乏饮食诱导的小鼠非酒精性脂肪性肝炎
Human PCSK9D374Y exacerbates methionine choline deficiency diet-induced nonalcoholic steatohepatitis in mice
摘要
Abstract
Objective To investigate the effect of mutation human proprotein convertase subtilism/kexin type 9(hPCSK9D374Y)in PCSK9 gene on methionine choline deficiency diet(MCD)-induced nonalcoholic steato-hepatitis(NASH)in mice.Methods Sixteen C57BL/6J wild-type mice were selected and randomly divided into the hPCSK9D374Y group and the control GFP group.MCD was fed for 6 weeks,and then the serum level of hepatic triglyceride,alanine aminotransferase(ALT)and aspartate aminotransferase(AST)was examined.Oil Red O and Sirius Red staining microscopy were used to identify hepatic lipid infiltration and fibrosis severity.F4/80-positive cell infiltration was analyzed using immunohistochemistry.Lipid synthesis and inflammatory response-related proteins were detected by Western blot and related mRNA expression was analyzed by RT-qPCR.Results Hepatic hPCSK9 protein and mRNA were significantly up-regulated,LDLR protein expression was down-regulated,and ser-um level of ALT and AST was significantly elevated in the hPCSK9D374Y group of mice(P＜0.05).The degree of he-patic steatosis and fibrosis increased and F4/80-positive cells were significantly increased(P＜0.01).FASN and SCD1 proteins were significantly up-regulated and PPARα was down-regulated in the hPCSK9D374Y group;The ex-pression of TLR4 and p-P65 was elevated,whereas the expression of Iκ Bα was decreased(P＜0.001).RT-qPCR re-sults showed a significant increase of mRNA coding inflammatory factors TNF-α,IL-1β,IL-6,and MCP-1,and a significant up-regulation of fibrosis-associated mRNAs(collagen Ⅰα and collagen Ⅲα)was found(P＜0.001).Conclusions Functionally acquired mutation in the PCSK9 gene(hPCSK9D374Y)exacerbates MCD-induced hepatic steatosis,inflammatory response and fibrosis in mice.关键词
非酒精性脂肪性肝炎/前蛋白转化酶枯草溶菌素9(PCSK9)/蛋氨酸胆碱缺乏饮食(MCD)/炎性因子Key words
non-alcoholic steatohepatitis/proprotein convertase subtilisin/kexin type 9(PCSK9)/methionine choline deficiency di-et/inflammatory factor分类
临床医学引用本文复制引用
阿比旦·阿卜杜如苏力,陈小翠,崔元峰,托罗娜依·米吉提,邓李惠,陈邦党..人源PCSK9D374Y加重蛋氨酸胆碱缺乏饮食诱导的小鼠非酒精性脂肪性肝炎[J].基础医学与临床,2025,45(5):637-643,7.基金项目
新疆维吾尔自治区自然科学基金重点项目(2022D01D16) （2022D01D16）
国家自然科学基金-新疆联合基金本地青年人才培养专项(U1903304) （U1903304）
