全反式维甲酸对兔动脉粥样硬化病灶中MCP-1 和TLR-4

目的:观察全反式维甲酸(ATRA)对兔颈动脉粥样硬化性病灶中内膜增生、MCP-1及TLR-4表达的影响,探讨其可能的抗炎机制。方法:新西兰雄性大白兔随机分为9组(n=6):对照组(A、B、C)、治疗组(A、B、C)、假手术组(A、B、C)。除假手术组外,其余两组给予高脂饮食2周后,对照组及治疗组给予颈动脉内膜空气干燥术损伤颈动脉内膜,假手术组分离暴露颈动脉但不损伤内膜,治疗组术前3天给予ATRA灌胃,直至处死。术后分别于7d、14d、28d处死。采取颈动脉标本,对血管粥样硬化病变进行形态学观察及测定,采用免疫组化法检测MCP-1及TLR-4表达水平。结果:从形态学观察及免疫组化检测看,对照组较假手术组内膜明显增生,MCP-1及TLR-4表达增多,治疗组内膜较对照组增生减轻,两种因子表达减少。结论:全反式维甲酸(ATRA)对兔颈动脉粥样硬化性病灶中的抗炎作用可能是通过抑制MCP-1及TLR-4等炎症因子的表达来发挥作用的。

The Effection of All-trans Retinoic Acid (ATRA) on the Expression of MCP-1 and TLR-4 in Atherosclerotic Lesions of Rabbits

Objective: To investigate the efficacy of ATRA on the tunica intima proliferation,the expression of MCP-1(monocyte chemotatic protein-1),TLR-4(Toll-like receptor4) in the injury and repair lesion located at the intima of the rabbit carotid artery,in order to study the possible mechanism of anti-inflammation of ATRA.Methods: New Zealand male rabbits were randomly divided into 9 groups(n=6) control group(ABC) experimental group(ABC),sham operated group(ABC).Except the sham operated group,the other two groups had been given high fat diet for two weeks.And the rabbits of control and experimental group were given air drying operation to injure the carotid artery intima.In the sham operated group,carotid arteries were dissected and exposed without injuring the intima.The rabbits of experimental group were not given ATRA intragastric administration three days before the operation until the execution.The rabbits of group A were put to death 7 days after the operation,group B 14 days,and group C 28 days.Then the specimens of carotid arteries were took the and the morphology of atherosclerotic lesions were detected and measured At last,the expression levels of MCP-1 and TLR-4 were detected by the method of immunohistochemisty.Results: ①In the control group,the intima started to proliferate 7 days after the air seasoning operation.After 14 /28 days the intima proliferated obviously with lumen stenosis,atheromatous plaque on the vessel wall and much expression of MCP-1 and TLR-4;②In the experimental group,the intima proliferated much less severely.14 and 28 days after the operation,the area of the proliferating intima was smaller(P<0.05),the opaque was thinner(P<0.05),and the positive expression of MCP-1 and TLR-4 was smaller(P<0.05) than those of the control group;③ In the sham operated group,the intima didn’t proliferate,MCP-1 and TLR-4 had little expression.Conclusions: ATRA alleviated the intima proliferation and lumen stenosis after the carotid artery intima injured by inhibiting the expression of MCP,TLR-4 and the other inflammatory factors probably.