巨噬细胞MED1缺失促进雌性ApoE和LDLR敲除小鼠动脉粥样硬化发展

Macrophage MED1 deficiency promotes the development of atherosclerosis in female ApoE and LDLR knockout mice

目的研究巨噬细胞MED1(mediator 1)缺失对雌性小鼠动脉粥样硬化的影响。方法利用ApoE敲除(ApoE^(-/-))、LDLR敲除(LDLR^(-/-))、MED1^(fl/fl)和巨噬细胞MED1敲除(MED1^(△Mac))小鼠,分别构建两种模型小鼠:ApoE和巨噬细胞MED1双敲除(MED1^(△Mac)/ApoE^(-/-))及MED1^(fl/fl)/ApoE^(-/-)对照小鼠;接受MED1^(△Mac)小鼠骨髓移植的LDLR^(-/-)(MED1^(△Mac)→LDLR^(-/-))和接受MED1^(fl/fl)小鼠骨髓移植的LDLR^(-/-)(MED1^(fl/fl)→LDLR^(-/-))对照小鼠。给予两种模型小鼠(雌性)饲喂西方饮食12周诱导动脉粥样硬化发生,动态测定小鼠体质量及血浆总胆固醇(TC)、总三酰甘油(TG)含量。饲喂12周后处死小鼠,对主动脉树和主动脉根部进行H&E和油红O染色,并计算斑块面积。结果与MED1^(fl/fl)/ApoE^(-/-)对照组小鼠相比,MED1^(△Mac)/ApoE^(-/-)实验组小鼠血浆TC和TG无明显差异,但其主动脉树和主动脉根部斑块面积显著增加。而且,与MED1^(fl/fl)→LDLR^(-/-)对照组小鼠相比,MED1^(△Mac)→LDLR^(-/-)实验组小鼠的主动脉树和主动脉根部斑块面积也有增加趋势。结论巨噬细胞MED1缺失促进雌性小鼠动脉粥样硬化发展。

Objective To study the effect of macrophage mediator 1(MED1)deficiency on atherosclerosis in female mice.Methods ApoE knockout(ApoE^(-/-)),LDLR knockout(LDLR^(-/-)),MED1^(fl/fl),and macrophage MED1 knockout(MED1^(△Mac))mice were recruited in the study.Two types of mouse model were constructed:ApoE and macrophage MED1 double knockout(MED1^(△Mac)/ApoE^(-/-))mice and their littermate controls(MED1^(fl/fl)/ApoE^(-/-)).(2)LDLR knockout(LDLR^(-/-))mice receiving bone marrow from MED1^(△Mac)(MED1^(△Mac)→LDLR^(-/-))or MED1^(fl/fl)(MED1^(fl/fl)→LDLR^(-/-))mice.Female mice from these two models were fed a Western diet(21%fat and 0.15%cholesterol)for 12 weeks to promote the development of atherosclerosis.Body weight,total cholesterol(TC),and total triglyceride(TG)content in plasma were measured dynamically.After Western diet feeding for 12weeks,aortic tree and aortic root were collected and hematoxylin-eosin(H&E)and oil red O staining were performed.Results Plasma TC and TG did not significantly differ between MED1^(fl/fl)/ApoE^(-/-)control group and MED1^(△Mac)/ApoE^(-/-)experimental group.However,the plaque area in aortic tree and aortic root was significantly increased in MED1^(△Mac)/ApoE^(-/-)mice.Moreover,compared with that in MED1^(fl/fl)→LDLR^(-/-)control group,the plaque area of aortic tree and aortic root had an increasing trend in MED1^(△Mac)→LDLR^(-/-)mice group.Conclusion MED1deficiency in macrophages promotes the development of atherosclerosis in female ApoE or LDLR knockout mice.