摘要
目的探究脯氨酸/丝氨酸丰富卷曲螺旋蛋白1介导的长链非编码RNA(lncLEPIS)过表达对血脂水平以及动脉粥样硬化发生发展的影响。方法16只ApoE-/-小鼠随机分为对照组(NC组)和lncLEPIS过表达组(lncLEPIS组),构建肝脏过表达lncLEPIS的高脂喂养的ApoE-/-小鼠模型。采用油红O染色评估小鼠主动脉粥样硬化斑块,用酶标法检测血脂水平,用实时荧光定量PCR检测胆固醇代谢相关基因的mRNA表达水平。结果NC组和lncLEPIS组的斑块面积/主动脉面积分别为(18.6%±0.3%)、(28.0%±1.3%),斑块面积/主动脉根部横截面积分别为(7.5%±0.2%)、(17.8%±0.3%),两组比较,差异具有显著性(P<0.05)。NC组和lncLEPIS组小鼠血浆甘油三酯水平分别为(0.65±0.07)mmol/L、(0.96±0.21)mmol/L,总胆固醇水平分别为(3.56±0.71)mmol/L、(7.36±0.65)mmol/L,高密度脂蛋白胆固醇水平分别为(1.46±0.05)mmol/L、(1.95±0.38)mmol/L,低密度脂蛋白胆固醇水平分别为(2.59±0.35)mmol/L、(5.59±0.59)mmol/L,两组比较,差异具有显著性(P<0.05)。与NC组相比,lncLEPIS组小鼠肝脏低密度脂蛋白受体(LDLR)表达水平下调48.4%,前蛋白转化酶枯草溶菌素9(PCSK9)表达水平上调62.8%(P<0.05)。结论lncLEPIS过表达降低LDLR表达,促进PCSK9表达,升高血浆LDLC水平,促进动脉粥样硬化发生发展。
Aim To explore the effect of proline/serine rich coiled coil protein 1-mediated long non-coding RNA(lncLEPIS)overexpression on blood lipid levels and the occurrence and development of atherosclerosis.Methods 16 ApoE-/-mice were randomly divided into control group(NC group)and lncLEPIS overexpression group(lncLEPIS group),and ApoE-/-mice fed with high-fat diet with liver lncLEPIS overexpression were constructed.Atherosclerotic plaques in mouse aorta were assessed by oil red O staining.Blood lipid levels were detected by enzyme labeling method.The mRNA expression levels of cholesterol metabolism-related genes were detected by real-time quantitative PCR.Results The plaque area/aortic area in the NC group and the lncLEPIS group were(18.6%±0.3%)and(28.0%±1.3%),and the plaque area/aortic root cross-sectional area were(7.5%±0.2%)and(17.8%±0.3%),the differences between the two groups was significant(P<0.05).The plasma triglyceride levels of the mice in the NC group and the lncLEPIS group were(0.65±0.07)mmol/L and(0.96±0.21)mmol/L,the total cholesterol levels were(3.56±0.71)mmol/L and(7.36±0.65)mmol/L,the high density lipoprotein cholesterol levels were(1.46±0.05)mmol/L and(1.95±0.38)mmol/L,and the low density lipoprotein cholesterol levels were(2.59±0.35)mmol/L and(5.59±0.59)mmol/L,the differences between the two groups were significant(P<0.05).Compared with the NC group,the expression level of low density lipoprotein receptor(LDLR)in the liver of mice was down-regulated by 48.4%in the lncLEPIS group,and the expression level of proprotein convertase subtilisin/kexin 9(PCSK9)was up-regulated by 62.8%(P<0.05).Conclusion Overexpression of lncLEPIS reduces the expression of LDLR,promotes the expression of PCSK9,increases the level of plasma LDLC,and promotes the occurrence and development of atherosclerosis.
作者
吕萍
潘杭雨
林荣湛
李钦贤
郭凯
郭志刚
LYU Ping;PAN Hangyu;LIN Rongzhan;LI Qinxian;GUO Kai;GUO Zhigang(Department of Cardiology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China;Department of Cardiology,Second People s Hospital of Guangdong Province,Guangzhou,Guangdong 510310,China)
出处
《中国动脉硬化杂志》
CAS
2022年第6期483-489,共7页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金青年项目(81900398)
广东省自然科学基金面上项目(2019A1515010666)。
