miR-224-3p靶向肿瘤坏死因子超家族成员14抑制脂质积累和动脉粥样硬化的研究  

miR-224-3p inhibits lipid accumulation and atherosclerosis by targeting TNFSF14

作　　者：陈泉润 蒋玉芹 刘鹏[2] 谢蒂立[2] CHEN Quan-run;JIANG Yu-qin;LIU Peng;XIE Di-li(School of Medicine,University of Electronic Science and Technology,Chengdu 610054,China;Department of Geriatric Cardiology,Sichuan Academy of Medical Science&Sichuan Provincial People′s Hospital,Chengdu 610072,China)

机构地区：[1]电子科技大学医学院,四川成都610054 [2]四川省医学科学院·四川省人民医院老年心血管科,四川成都610072

出　　处：《实用医院临床杂志》2022年第6期1-6,共6页Practical Journal of Clinical Medicine

基　　金：四川省干部保健科研课题(编号:川干研2018-223)。

摘　　要：目的 探究miR-224-3p靶向肿瘤坏死因子超家族成员14(TNFSF14)对动脉粥样硬化的影响。方法 分析miR-224-3p和TNFSF14在体内和体外的表达;miR-224-3p和TNFSF14的靶向关系;体外转染后,测定THP-1细胞内甘油三酯和胆固醇含量;检测细胞内脂质的积累;分析脂质代谢相关蛋白的表达。在体内,动脉粥样硬化小鼠尾静脉注射miR-224-3p agomir及其阴性对照agomir NC,分析miR-224-3p对动脉粥样硬化小鼠主动脉病变和脂质积聚的影响。结果 miR-224-3p在AS患者和氧化低密度脂蛋白(ox-LDL)处理的THP-1细胞中的表达均降低,TNFSF14的表达升高(P<0.05)。miR-224-3p过表达组TNFSF14表达下调(P<0.05)。与对照组比较,ox-LDL刺激后细胞内脂滴显著增多,清道夫受体、乙酰辅酶A乙酰转移酶1和脂肪生成基因的表达显著增加(P<0.05),脂肪分解基因的表达显著减少(P<0.05),TNFSF14过表达后上述效应进一步增强(P<0.05),miR-224-3p明显抑制TNFSF14过表达的增强效应(P<0.05)。体内结果显示miR-224-3p过表达后主动脉弓区域动脉粥样斑块和脂质沉积明显减少,胶原蛋白含量显著增加(P<0.05)。结论 miR-224-3p可能通过靶向TNFSF14抑制动脉粥样硬化小鼠或ox-LDL刺激的THP-1巨噬细胞中脂质的积累。Objective To explore the effect of miR-224-3 p targeting TNFSF14 on atherosclerosis(AS).Methods The expressions of miR-224-3 p and TNFSF14 in vitro and in vivo were analyzed. Targeting relationship between miR-224-3 p and TNFSF14 was analyzed. After transfection in vitro, the contents of TG and TC in THP-1 cells were measured. Oil red O staining was used to detect intracellular lipid accumulation. The expressions of lipid metabolism related-proteins were analyzed by Western blotting. In vivo, ApoE knockout mice were fed with high-fat diet to induce AS, and miR-224-3 p agomir and its negative control(agomir NC) were injected intravenously to analyze the effects of miR-224-3 p on aortic lesions and lipid accumulation in AS mice.Results Compared with control group, expression of miR-224-3 p was decreased in both AS mice and ox-LDL treated THP-1 cells, while the expression of TNFSF14 was increased(P<0.05). The expression of TNFSF14 was down-regulated in the miR-224-3 p overexpression group(P<0.05). Compared with the control group, lipid droplets in the cells were significantly increased after ox-LDL stimulation, and the expressions of scavenger receptor(SR-A), acyl-CoA:cholesterol acyltransferase-1(ACAT1) and adipogenic genes(ACS) were significantly increased(P<0.05). The expressions of adipogenic genes(PPARa and CPT-1) were significantly decreased(P<0.05). The above effects were further enhanced after TNFSF14 overexpression(P<0.05), and miR-224-3 p significantly inhibited the enhanced effect of TNFSF14 overexpression(P<0.05). The results in vivo showed that after overexpression of miR-224-3 p, the atherosclerotic plaque and lipid deposition in aortic arch region were significantly reduced, and the collagen content was significantly increased(P<0.05).Conclusion miR-224-3 p inhibits the lipid accumulation in AS mice or ox-LDL-stimulated THP-1 macrophages through targeting TNFSF14.

关 键 词：miR-224-3p 肿瘤坏死因子超家族成员14 脂质积累 动脉粥样硬化 

分 类 号：R541.4[医药卫生—心血管疾病]