消退素D1在小鼠主动脉夹层中的作用及机制研究

Role of resolvin D1 in aortic dissection and its molecular mechanism

目的探讨消退素D1(resolvin D1,RvD1)在小鼠主动脉夹层中的作用及机制研究。方法SPF级雄性小鼠40只,随机分成对照组、RvD1组、β氨基丙腈(BAPN)组和BAPN+RvD1组,每组10只,BAPN组和BAPN+RvD1组构建BAPN饮食诱导的小鼠主动脉夹层模型,对照组和RvD1组饲喂普通的小鼠维持饲料,RvD1组和BAPN+RvD1组腹腔注射RvD1 3μg/(kg·d),对照组和BAPN组注射等量生理盐水。用苏木精-伊红和血管弹力纤维染色(EVG)观察主动脉和弹力纤维的形态和结构,用ELISA法检测血清白细胞介素(IL)1、IL-17、TNF-α和γ干扰素水平,采用RT-PCR法检测主动脉组织IL-1、IL-17、TNF-α和γ干扰素mRNA表达。结果对照组和RvD1组均未出现主动脉夹层,而BAPN+RvD1组小鼠主动脉夹层发生率和病死率显著低于BAPN组,差异有统计学意义(20.0%vs 70.0%,10.0%vs 40.0%,P<0.05);苏木精-伊红染色和EVG结果提示,BAPN组小鼠血管壁增厚,伴假腔形成,同时中膜弹力纤维出现明显的断裂或中断,而BAPN+RvD1组血管壁仅轻度增厚,未见假腔形成;与对照组比较,BAPN组小鼠血清IL-1、IL-17、TNF-α、γ干扰素和主动脉IL-1、IL-17、TNF-α、γ干扰素mRNA表达水平明显升高(P<0.05,P<0.01),而BAPN+RvD1组血清IL-1、IL-17、TNF-α、γ干扰素水平和主动脉IL-1、IL-17、TNF-α和γ干扰素mRNA表达明显低于BAPN组,差异有统计学意义(P<0.05,P<0.05)。结论RvD1可显著降低循环和主动脉炎症,防止中膜弹力纤维和主动脉的断裂,降低主动脉夹层的发生。

Objective To study the role of resolvin D1(RvD1)in aortic dissection and its mechanism.Methods Forty male mice were randomly divided into control group,RvD1 group,BAPN group,and BAPN+RvD1 group(10 in each group).An aortic dissection model of mice was established for BAPN group and RvD1 group.The mice in control group and RvD1 group were fed on common mouse forages.The mice in RvD1 group and BAPN+RvD1 group received intra-abdominal injection with RvD1 at the dose of 3μg/(kg·d)while those in control group and BAPN group received intra-abdominal injection with the same dose of normal saline.The morphology and structure of aorta were observed with HE and EVG staining.The expressions of IL-1,IL-17,TNF-αand IFN-γwere detected by ELISA and the mRNA expressions of IL-1,IL-17,TNF-αand IFN-γwere detected by RT-PCR.Results No aortic dissection was found in control group and RvD1 group.The incidence and mortality of aortic dissection were significantly lower in BAPN+RvD1 group than in BAPN group(20.0%vs 70.0%,10.0%vs 40.0%,P<0.05).HE and EVG staining showed that the blood vessel wall was thicker with formation of pseudal cavities and rupture of elastic fibers in BAPN group while the blood vessel wall was slightly thicker in BAPN+RvD1 group without formation of pseudal cavities.The expression levels of IL-1,IL-6,IL-17 and TNF-αand the mRNA expression levels of IL-1,IL-6,IL-17 and TNF-αwere significantly higher in BAPN group than in control group(P<0.05,P<0.01)and were significantly lower in BAPN+RvD1 group than in control group(P<0.05,P<0.01).Conclusion RvD1 can significantly reduce the circulation and inflammation of aorta,prevent the rupture of elastic fibers and aorta,and reduce the incidence of aortic dissection in mice.