法舒地尔对自发高血压大鼠血压的作用及其机制研究  

The effect and mechanism of fasudil on spontaneous hypertension in rats

作　　者：范彦夫[1] 张志英 韩秀红[3] 杜淑华[4] 齐建祥[1] 邵伟然[4] 赵秀芹[4] 王春敏[5] Fan Yanfu;Zhang Zhiying;Han Xiuhong;Du Shuhua;Qi Jianxiang;Shao Weiran;Zhao Xiuqin;Wang Chunmin(Department of Cardiology,The Second Affiliated Hospital of Jiamusi University,Jiamusi 154002,China;Department of Physical Diagnosis,Renhe Hospital of Jiamusi,Jiamusi 154002,China;Department of Neurology,The Second Affiliated Hospital of Jiamusi University,Jiamusi 154002,China;Department of Emergency,The Second Affiliated Hospital of Jiamusi University,Jiamusi 154002,China;Department of Microbiology,School of Basic Medicine,Jiamusi University,Jiamusi 154007,China)

机构地区：[1]黑龙江省佳木斯大学附属第二医院心内科,佳木斯154002 [2]黑龙江省佳木斯市仁和医院物理诊断科,佳木斯154002 [3]黑龙江省佳木斯大学附属第二医院神经内科,佳木斯154002 [4]黑龙江省佳木斯大学附属第二医院急诊科,佳木斯154002 [5]黑龙江省佳木斯大学基础医学院微生物教研室,佳木斯154007

出　　处：《广西医科大学学报》2018年第3期315-318,共4页Journal of Guangxi Medical University

基　　金：佳木斯大学科学技术校级面上项目(No.13Z1201557)

摘　　要：目的:探讨法舒地尔对自发高血压(SHR)大鼠血压的作用及其机制。方法:将30只SHR大鼠随机分为5组:模型组、硝苯地平组(10mg/kg灌胃),法舒地尔低、中、高剂量组(分别为5mg/kg、10mg/kg、20mg/kg灌胃),每组6只。另取6只健康WKY大鼠作为空白组。模型组和空白组均灌胃给予等量生理盐水。对比不同时刻各组尾动脉收缩压(SBP)、治疗8周后血清一氧化氮(NO)和内皮素-1(ET-1)水平、左心室重量指数(LVWI)、心脏、肾脏以及主动脉组织RhoA和Rho激酶mRNA相对表达量。结果:干预后2周、4周、6周、8周,硝苯地平组、法舒地尔中、高剂量组大鼠尾动脉SBP均显著低于模型组(P<0.05),且法舒地尔高剂量组SBP低于中剂量组和硝苯地平组(P<0.05)。干预后各时间点,6组大鼠尾动脉SBP、血清NO水平、LVWI及不同组织RhoA和Rho激酶mRNA相对表达量由低至高为空白组、法舒地尔高剂量组、法舒地尔中剂量组、硝苯地平组、法舒地尔低剂量组、模型组,而血清ET-1水平相反,组间比较差异均有统计学意义(均P<0.05)。结论:法舒地尔能有效降低SHR大鼠尾动脉SBP,且在一定范围内剂量越高效果越理想,推测与降低RhoA和Rho激酶mRNA的表达,调控血清NO和ET-1水平有关。Objective:To investigate the effect and mechanisms of fasudil on spontaneous hypertension(SHR)in rats.Methods:A total of 30 SHR rats were randomly divided into 5 groups(n=6 per group):model group,nifedipine group(10 mg/kg nifedipine via gavage),and fasudil low-medium-and high-dose groups(respectively 5 mg/kg,10 mg/kg and 20 mg/kg fasudil via gavage).Six healthy WKY rats were se-lected as a normal control group.The rats in the model group and the normal control group were given equal volume of saline via gavage.The systolic caudal arterial pressure,left ventricular mass index(LVWI),the serum levels of nitric oxide(NO)and endothelin-1(ET-1)as well as the mRNA expressions of RhoA and Rho kinase in myocardium,kidney and aorta were detected.Results:The systolic caudal arterial pressure was significantly decreased by treatment of nifedipine or fasudil for 2,4,6 and 8 weeks(P〈0.05),and was low-er in high-dose fasudil group compared with nifedipine group and medium-dose fasudil group(P〈0.05).After treatment,the systolic caudal arterial pressure,NO level,LVWI and the mRNA expressions of RhoA and Rho kinase in myocardium,kidney and aorta from lowest to highest as follows:normal control group〉high-dose fasudil group〉medium-dose fasudil group〉nifedipine group〉low-dose fasudil group〉model group,while the serum ET-1 level was the opposite.There were significant differences among groups(P〈0.05).Conclusion:Fasudil could effectively reduce the systolic caudal arterial pressure in SHR rats,and was dose-dependent in a certain?the mechanisms might be associated with the reduced expressions of RhoA and Rho kinase,and regulation of serum NO and ET-1 levels.

关 键 词：法舒地尔 自发高血压 左心室重量指数 作用机制 

分 类 号：R544.1[医药卫生—心血管疾病]