Rho激酶在小型猪白介素-1β介导的冠状动脉痉挛中的作用机制  

Upregulated Rho-kinase and increased phosphorylation of myosin-binding subunit of myosin phosphates are key players in a porcine coronary artery spasm model with interleukin-1β

作　　者：关启刚[1] 曾定尹[1] 孙喜琢[2] 苗志林[1] 周旭晨[1] 何学志[2] 韩凤桐[2] 程颖[1] 张利[2] 

机构地区：[1]中国医科大学附属第一医院循环内科,沈阳110001 [2]大连市中心医院心内科

出　　处：《中华心血管病杂志》2006年第1期50-53,共4页Chinese Journal of Cardiology

基　　金：国家重点研究发展计划(973计划)资助项目(2005CB523310)

摘　　要：目的探讨Rho激酶途径在冠状动脉痉挛发病中的作用机制。方法小型雄性家猪随机分为对照组(n=8)和模型组(n=8),冠状动脉外膜分别包裹吸附含生理盐水和白介素(IL)-1β琼脂糖微粒悬液的纸巾。2周后,采用冠状动脉造影观察管腔狭窄程度及5-羟色胺诱发冠状动脉痉挛情况。测定冠状动脉包裹血管段Rho激酶mRNA表达、肌球蛋白结合亚基磷酸化表达及光镜病理学改变。结果冠状动脉外膜包裹IL-1β血管段发生不同程度的管腔狭窄,5-羟色胺可诱发病变血管段痉挛。模型组与对照组相比,Rho激酶的mRNA表达病变血管段明显上调[(98·20±7·66)%对(63·70±4·26)%,P<0·05];肌球蛋白轻链磷酸酶的肌球蛋白结合亚基磷酸化表达升高(25485±4745对6510±779,P<0·05)。光镜可见病变血管段内膜增殖及炎症细胞聚集现象。结论Rho激酶参与IL-1β介导的冠状动脉痉挛的发生,其可能是通过增加肌球蛋白结合亚基磷酸化水平,抑制肌球蛋白轻链磷酸酶活性及加强钙增敏途径所致。Objective Phosphorylation of myosin light chain （MLC） is one of the most important steps for vascular smooth muscle contraction and Rho-kinase is involved in this process. We investigated the role of Rho-kinase in a porcine coronary artery spasm model with interleukin-1β. Methods Segments of left coronary artery adventitia were surrounded by normal saline （n =8） or IL-1β agarose mierone （n =8） for 2 weeks. Vasospastie responses to intraeoronary serotonin or histamine then studied at the saline or IL-1β-treated site. The Rho-kinase mRNA expression in the treated site was measured by reverse transcription-polymerase chain reaction analysis （RT-PCR）. The extent of phosphorylation of myosin-binding subunit of myosin phosphates （MBS, one of the major substrates of Rho-kinase） were quatified by Western blot analysis. ResuRs Intracoronary serotonin or histamine repeatedly induced coronary artery spasm and coronary arterial stenosis was evidenced at IL-1β-treated site. Expression of Rho-kinase mRNA in IL-1β- treated site was significantly increased compared to saline treated site （98.20% ± 7. 66% vs. 63. 70% ± 4. 26% ,P 〈0. 05 ）. Western blot analysis showed that during the serotonin-induced contractions the extent of phosphorylation of MBS was also significantly increased in the spastic site （25 485 ± 4745 vs. 6510 ± 779,P 〈 0. 05）. Conclusion Rho-kinase upregulation at the spastic site and increased phosphorylafion of myosin-binding subunit of myosin phosphates are key players in inducing vascular smooth muscle hypercontracfion in this porcine model.

关 键 词：冠状血管痉挛 磷酸转移酶类 白细胞介素1 

分 类 号：R543.3[医药卫生—心血管疾病]