过表达CTRP9抑制ApoE基因敲除小鼠肝脏脂肪病变  

Overexpression of CTRP9 Attenuates Hepatic Steatosis in Apolipoprotein E Deficient Mice

作　　者：李向宇 艾乐乐 刘玉琪 梁国朵 相奥琪 陈晓畅 余琦 关华 LI Xiang-yu;AI Le-le;LIU Yu-qi;LIANG Guo-duo;XIANG Ao-qi;CHEN Xiao-chang;YU Qi;GUAN Hua(Shaanxi Provincial Key Laboratory of Ischemic Cardiovascular Disease&Institute of Basic and Translational Medicine of Xi’an Medical University,Xi’an 710021,China;Animal Center of Medical College,Xi’an Jiaotong University,Xi’an 710067,China)

机构地区：[1]西安医学院基础与转化医学研究所,陕西省缺血性心血管疾病重点实验室,西安710021 [2]西安交通大学医学部实验动物中心,西安710067

出　　处：《南昌大学学报（医学版）》2023年第2期1-7,共7页Journal of Nanchang University：Medical Sciences

基　　金：陕西省教育厅重点科研计划项目(22JS031,22JS033,20JS142);陕西省科技厅科研计划项目(2021JQ-785);大学生创新创业计划项目(121520027)。

摘　　要：目的研究C1q/肿瘤坏死因子相关蛋白9(CTRP9)对高脂血症模型载脂蛋白E基因敲除(ApoE^(-/-))小鼠肝脏脂肪病变形成的影响及机制。方法将30只8周龄雄性ApoE^(-/-)小鼠随机分为对照组与观察组,每组15只,对照组小鼠给予尾静脉注射腺病毒空载绿色荧光蛋白(Ad-GFP),观察组小鼠给予尾静脉注射腺病毒载CTRP9(Ad-CTRP9),高脂高胆固醇饮食(HF/HC)饲喂12周后,采集尾静脉血,处死小鼠收集肝脏组织。采用HE、油红O染色观察CTRP9对ApoE^(-/-)小鼠肝脏脂肪病变形成的影响;采用real time PCR检测CTRP9及脂质合成、炎症相关和线粒体氧化磷酸化相关基因的表达水平;采用western blotting技术检测肝脏组织中CTRP9蛋白表达水平。结果与对照组相比,过表达CTRP9小鼠(观察组)体重和血脂水平差异无统计学意义(P>0.05),CTRP9基因和蛋白表达水平显著升高(P<0.05),肝脏脂肪病变显著减少(P<0.05),肝脏组织中甘油三酯和总胆固醇水平显著下降(P<0.05),脂质合成(FAS、SCD1、SREBP1c)以及炎症相关基因(MCP-1、MIP1α和IL-1β)表达水平显著下调(P<0.01或P<0.001),而脂质代谢(PPARα、PPARγ、LXRα和LXRβ)及线粒体氧化磷酸化相关基因(CPT1、CPT2、COX4、Cytoc、Acadl和Acadm)表达水平显著增加(P<0.05或P<0.01)。结论过表达CTRP9能够抑制肝脏组织中脂肪生成以及炎症反应,同时促进肝细胞脂肪酸氧化磷酸化和能量代谢,增加线粒体能量消耗,从而降低肝脏组织中脂质蓄积。Objective To study the effect and mechanism of C1q/tumor necrosis factor-related protein 9(CTRP9)on hepatic steatosis in apolipoprotein E deficient(ApoE^(-/-))mice with hyperlipidemia.Methods Thirty male ApoE^(-/-)mice were randomly injected with adenovirus vectors carrying either green fluorescent protein(control group)or CTRP9(observation group)through the tail vein,with 15 mice in each group.After the mice were fed a high-fat/high-cholesterol diet for 12 weeks,blood samples were drawn from the tail vein,and liver tissues were collected.The effect of CTRP9 on the formation of hepatic steatosis was observed by HE and Oil Red O staining.The expression levels of CTRP9 gene and lipid synthesis-,inflammation-and mitochondrial oxidative phosphorylation-related genes were detected by real time PCR.The expression of CTRP9 protein in the liver was measured by Western blotting.Results There were no significant differences in body weight and plasma lipid levels between the two groups(P>0.05).Compared with the control group,the expression levels of CTRP9,and lipid metabolism(PPARα,PPARγ,LXRαand LXRβ)and mitochondrial oxidative phosphorylation-related genes(CPT1,CPT2,COX4,Cytoc,Acadl and Acadm)were increased,hepatic steatosis and triglyceride and total cholesterol contents were reduced,and the expression levels of lipid synthesis-related genes(FAS,SCD1,SREBP1c)and inflammation-related genes(MCP-1,MIP1αand IL-1β)were down-regulated in the observation group(P<0.05 or P<0.01 or P<0.001).Conclusion Overexpression of CTRP9 can reduced lipid accumulation in the liver by inhibiting adipogenesis and inflammation,promoting oxidative phosphorylation of fatty acids and energy metabolism,and increasing mitochondrial energy consumption.

关 键 词：C1q/肿瘤坏死因子相关蛋白9 肝脏 氧化磷酸化 脂质代谢 载脂蛋白E基因敲除 动物 实验 小鼠 

分 类 号：R-332[医药卫生] R575