AT1受体在同型半胱氨酸致动脉粥样硬化斑块不稳定性中的作用机制研究*

Role of AT1 receptor in instability of atherosclerotic plaque caused by homocysteine*

摘要:

目的 探究血管紧张素Ⅱ1型受体（AT1）在同型半胱氨酸（Hcy）导致动脉粥样硬化斑块不稳定性中的作用。方法 将21只6周龄雄性载脂蛋白基因敲除小鼠随机分为对照组（CTL组）、高同型半胱氨酸组（HHcy组）和高同型半胱氨酸+替米沙坦组（HHcy+TLM组），每组7只，共饲养12周。治疗前后测量各组体重、收缩压（SBP）。饲养12周后，摘眼球取血，检测血脂和Hcy。油红O染色主动脉根部斑块；免疫组织化学SP法检测斑块内炎症因子白细胞介素-6（IL-6）、单核细胞驱化蛋白-1（MCP-1）、巨噬细胞表面分子（mac-3）、基质金属蛋白酶-9（MMP-9）的表达水平；Masson染色胶原蛋白。结果 HHcy组的主动脉根部斑块面积大于CTL组（P?<0.05），IL-6、MCP-1、MMP-9、mac-3的表达水平高于CTL组（P?<0.05），而胶原含量低于CTL组（P?<0.05）；HHcy+TLM组斑块面积小于HHcy组，IL-6、MCP-1、MMP-9、mac-3的表达水平低于HHcy组，胶原含量高于HHcy组（P?<0.05）；HHcy+TLM组的SBP及体重与HHcy组比较，差异有统计学意义（P?<0.05），HHcy+TLM组降低。结论 Hcy可促进动脉粥样硬化斑块发展且影响斑块的稳定性，而替米沙坦有逆转Hcy的作用，其机制可能是通过AT1受体实现的。

Abstract:

Objective To explore the role of Angiotensin II type 1 receptor (AT1) in the instability of atherosclerotic plaques caused by Homocysteine (Hcy). Methods Twenty-one 6-week-old male ApoE-/- mice were weighed and divided into three groups according to the random number table: control group, HHcy group, HHcy telmisartan treatment (TLM) group (10?mg/kg gavage treatment). Weight and blood pressure were measured before and after 12 weeks of feeding. The blood specimen was retained by removing the eyeball. Plasma Hcy was detected by using cyclic enzyme method. Oil red O staining was used to measure the area of aortic root plaque, and immunohistochemical SP method was used to detect plaque inflammatory factor interleukin-6 (IL-6), Monocytes chemoprotein-1 (MCP-1), macrophage surface molecules (mac-3), matrix metalloproteinase-9 (MMP-9), and collagen was stained by Masson staining. Results The plaque area of HHcy group was significant larger than that of control group. The expression levels of IL-6, MCP-1, mac-3 and MMP-9 in plaque were higher in HHcy group than control group (P?