瑞舒伐他汀通过NO/eNOS信号通路改善慢性心力衰竭大鼠的心功能  

Rosuvastatin Improves Cardiac Function of Rats with Chronic Heart Failure via NO/eNOS Signaling Pathway

作　　者：徐清斌[1] 熊爱琴 徐烨华 王洋[3] 马萍[1] 

机构地区：[1]宁夏医科大学心脑血管医院心内科,银川750004 [2]宁夏医科大学临床学院,银川750004 [3]宁夏医科大学药学院,银川750004

出　　处：《华中科技大学学报（医学版）》2015年第2期160-164,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81060024)

摘　　要：目的探讨瑞舒伐他汀(ROS)通过一氧化氮(NO)/内皮型一氧化氮合酶(eNOS)信号通路对慢性心力衰竭大鼠心功能的保护作用及其机制。方法 Sprague-Dawley(SD)大鼠,皮下注射异丙肾上腺素[ISO,5mg/(kg·d)]连续给药7d诱发大鼠慢性心力衰竭,瑞舒伐他汀组[ROS,5mg/(kg·d)]于第1天皮下注射ISO开始同时予以灌胃给药至第7天,停止ISO皮下注射,第8天继续给予ROS灌胃至第14天。检测血流动力学参数和心肌NO含量并观察心肌组织病理变化,采用Western blot法检测心肌eNOS的蛋白表达。结果 1瑞舒伐他汀显著改善ISO诱导的慢性心力衰竭大鼠心脏血流动力学参数,与ISO组比较,瑞舒伐他汀组显著升高左心室收缩压(LVSP)和左心室最大上升速率(+LV dP/dtmax)(P<0.01),显著降低左心室最大下降速率(-LV dP/dtmin)(P<0.01)。2瑞舒伐他汀可改善ISO诱导的慢性心力衰竭大鼠心肌组织病理损害,与ISO组比较,瑞舒伐他汀的治疗可缩小心肌纤维化面积,减轻炎性细胞浸润及心肌细胞水肿,减轻毛细血管扩张。3在慢性心力衰竭大鼠心肌组织中,瑞舒伐他汀显著升高ISO诱导减低的NO含量(P<0.01)。4瑞舒伐他汀组与ISO组比较,增加ISO诱导降低的心肌组织eNOS蛋白的表达(P<0.01)。结论瑞舒伐他汀可改善ISO诱导慢性心力衰竭大鼠的心功能,其机制可能与NO/eNOS信号转导通路有关。Objective To investigate the protective role of rosuvastatin in cardiac function of rats with isoproterenol（ISO）-induced chronic heart failure and its mechanism.Methods Male Sprague-Dawley rats were given ISO[5mg/（kg·d）,subcutaneous injection]for consecutive 7days to induce chronic heart failure.Besides,rats were treated with rosuvastatin 5mg/（kg·d）by gavage for 14 days in rosuvastatin group.Blood dynamic parameters and NO levels in heart tissues were detected.Histopathological changes in heart tissues were observed.Western blot was used to determine the level of eNOS protein.Results Rosuvastatin could significantly improve the cardiovascular dynamic parameters of rats with ISO-induced chronic heart failure.LVSP and＋LV dP/dtmaxwere conspicuously increased and-LV dP/dtminsignificantly decreased in rosuvastatin group when compared with ISO group（P〈0.01 for all）.Moreover,rosuvastatin could significantly attenuate myocardial pathological changes of rats with chronic heart failure.The myocardial fibrosis area was significantly reduced,and the infiltration of inflammatory cells,myocyte swelling and capillary dilation were significantly ameliorated in rosuvastatin group compared with ISO group.Furthermore,rosuvastatin significantly increased the NO content and the expression levels of eNOS protein in heart tissues（P〈0.01）.Conclusion Rosuvastatin may improve the cardiac function of rats with ISO-induced chronic heart failure via NO/eNOS signal transduction pathway.

关 键 词：瑞舒伐他汀 异丙肾上腺素 一氧化氮 内皮型一氧化氮合酶 

分 类 号：R54[医药卫生—心血管疾病]