剪切因子Im25在血管平滑肌细胞中的缺失对小鼠高脂血症的影响

Effects of cleavage factor Im25 downregulation in vascular smooth muscle cells on hyperlipidemia in mice

目的探讨剪切因子Im25(CFIm25)在平滑肌细胞(VSMCs)中的缺失对高脂血症的影响.方法构建VSMCs中特异性敲除CFIm25的小鼠(CFIm25^(f/+)TaglnCre)和对照小鼠(TaglnCre)模型;通过对两种不同基因型的小鼠喂养正常饮食或高脂肪饮食(HFD)18周,监测小鼠的体重变化;采用ELISA法检测血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)水平;采用油红O染色评估小鼠主动脉脂质沉积程度.结果HFD喂养期间,CFIm25^(f/+)TaglnCre小鼠体重明显高于对照组[雄性:(1.01±0.06)g和(0.87±0.31)g,t=7.53,P<0.05;雌性:(0.64±0.02)g和(0.35±0.04)g,t=9.68,P<0.05];HFD喂养18周后,CFIm25^(f/+)TagInCre小鼠的TC[(6.80±0.35)mmol/L和(3.76±0.87)mmol/L,t=5.63,P=0.004]、TG[(0.97±0.21)mmol/L和(0.42±0.10)mmol/L,t=4.08,P=0.015]和LDL-C[(5.20±0.30)mmol/L和(2.00±0.98)mmol/L,t=5.40,P=0.006]水平均高于TaglnCre组,其中TC增加80.72%,TG增加132.79%,LDL-C增加160.32%;CFIm25f/+TaglnCre小鼠主动脉中脂质沉积明显增多,粥样硬化斑块面积增加(均P<0.05).结论小鼠VSMCs中CFIm25的缺失加重了高脂血症,并加速了动脉粥样硬化病变形成.

Objective To investigate the impact of cleavage factor Im25(CFIm25)on VSMCs-specific knockdown in the context of hyperlipidemia.Methods Mice models were constructed with specific knockout of CFIm25 in VSMCs(CFIm25f/+TaglnCre)and control mice(TaglnCre).The mice were fed a normal diet or high-fat diet(HFD)for 18 weeks and their body weight changes were monitored.ELISA was used to measure serum total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein(HDL-C)and low-density lipoprotein(LDL-C)levels.The extent of aortic lipid deposition in mice was assessed by oil red O staining.Results During the feeding of a high-fat diet,CFIm25f/+TaglnCre mice showed a significant increase in body weight compared to the control group[Male(1.01±0.06)g and(0.87±0.31)g,t=7.53,P<0.05;Female:(0.64±0.02)g and(0.35±0.04)g,t=9.68,P<0.05].After 18 weeks of high-fat diet feeding,CFIm25f/+TaglnCre mice had significantly higher levels of TC[(6.80±0.35)mmol/L and(3.76±0.87)mmol/L,t=5.63,P=0.004],TG[(0.97±0.21)mmol/L and(0.42±0.10)mmol/L,t=4.08,P=0.015],and LDL-C[(5.20±0.30)mmol/L and(2.00±0.98)mmol/L,t=5.40,P=0.006]compared to the TaglnCre group.Specifically,TC levels increased by 80.72%,TG increased by 132.79%,and LDL-C increased by 160.32%.There was a significant increase in aorta lipid deposition and atherosclerotic plaque area in CFIm25f/+TaglnCre mice(P<0.05).Conclusions The research indicated that VSMCs-specific CFIm25 knockdown in mice further worsened hyperlipidemia and atherosclerotic lesions.