Rho激酶在糖尿病血管内皮功能改变中的作用  

Role of Rho kinase in diabetic vascular endothelial dysfunction

作　　者：吴健美[1] 陈晓娜[1] 郭正祥[1] 纪晓微[1] 施巧雅[1] 尹洪萍[1] 沈礼[1] 汝海龙[1] 林国华[1] 刘传飞[1] 刘翠清[1] 

机构地区：[1]杭州师范大学基础医学部生理教研室,浙江杭州310036

出　　处：《中国病理生理杂志》2012年第6期1103-1108,共6页Chinese Journal of Pathophysiology

基　　金：浙江省教育厅自然科学研究项目(No.Y200906789);杭州市医疗项目(No.20100633B10);浙江省新苗人才培养计划(No.2010R421028)

摘　　要：目的:探讨Rho激酶激活在糖尿病血管内皮功能损伤中的作用。方法:利用正常SD大鼠、基因型糖尿病动物模型和高脂饮食诱发的小鼠肥胖模型,用器官浴槽和肌动描记方法对血管功能进行检测,用免疫印迹方法对血管组织中内皮型一氧化氮合酶(eNOS)磷酸化水平进行测定,用ELISA方法对血管组织中血栓烷受体(TP受体)激活物进行测量。结果:TP受体激活可以抑制正常血管的内皮依赖性舒张,使最大舒张值(Emax)由正常组的(78.8±10.6)%降到(17.9±5.1)%;Rho激酶抑制剂预处理翻转了TP受体的抑制作用,Emax值为(62.0±11.2)%;抑制eNOS抵消了Rho激酶抑制剂对血管功能的改善作用。与此相一致,TP受体激活可以抑制正常血管eNOS磷酸化水平,并且该作用被Rho激酶抑制剂所翻转。此外,抑制Rho激酶可以使糖尿病小鼠和肥胖小鼠的血管内皮依赖性舒张作用得到改善,Emax值显著增加。并且,与对照组相比,糖尿病动物血管组织中血栓烷B2和前列腺素F2α水平升高。结论:Rho激酶参与了糖尿病血管内皮功能紊乱的调节,可能与TP受体激活和抑制eNOS活性有关。AIM： To investigate the role of Rho kinase in diabetic vascular endothelial dysfunction. METHODS： SD rats, genetic db/db diabetic model and high-fat diet-induced obese mice were used in this study. The thoracic aorta of the rats or mice were isolated and suspended in organ bath or myograph for measurement of the changes in isometric tensions. The levels of phosphorylated endothelial nitric oxide synthase（eNOS） were determined by Western blotting. Thromboxane B2（TXB2）,prostaglandin F2α（PGF2α） and thromboxane receptor （TP receptor） activators in artery were measured by ELISA. RESULTS： Endothelium-dependent vasorelaxation was attenuated by TP receptor activation, which was ameliorated by Rho kinase inhibitors. The improved endothelium-dependent vasorelaxation by inhibition of Rho kinase was abolished by pretreatment with the inhibitor of eNOS. Consistently, the level of phosphorylated eNOS was inhibited by TP receptor activation, which was reversed by inhibition of Rho kinase. The endothelium-dependent vasorelaxation was also improved by Rho kinase inhibitors in diabetic and obese animals. The levels of TXB2 and PGF2α in the arteries were increased in diabetic animals compared with the controls. CONCLUSION： Rho kinase plays a role in diabetic endothelial dysfunction, which may be related to TP receptor activation and eNOS inhibition.

关 键 词：RHO激酶 受体 血栓烷 内皮 血管 糖尿病 

分 类 号：Q463[生物学—生理学]