Rho激酶抑制剂对自发性高血压大鼠血压的影响  

Effects of Rho-kinase inhibitor on blood pressure in spontaneously hypertensive rats

作　　者：张志杰[1] 范彦夫[2] 张志英 谢培益[1] 方红城[1] 

机构地区：[1]广东医学院附属南山医院心内科,深圳518052 [2]佳木斯大学附属口腔医院心内科 [3]佳木斯仁和医院超声科

出　　处：《临床心血管病杂志》2013年第6期463-466,共4页Journal of Clinical Cardiology

摘　　要：目的:研究Rho激酶抑制剂对自发性高血压大鼠(SHR)血压的影响。方法:30只SHR随机分为5组:SHR对照组(SHR组),法舒地尔低剂量组(SHRL组)、中剂量组(SHRM组)、大剂量组(SHRH组)和硝苯地平组(XBDP组),每组6只;另取6只Wistar-Kyoto大鼠(WKY组)作为正常对照组(WKY组)。给药共8周,分别测量治疗前后尾动脉收缩压(SBP),测定血浆一氧化氮(NO)、内皮素(ET)-1水平,及主动脉和心肌组织中Rho激酶mRNA的表达。结果:用药前SHR各组SBP水平差异无统计学意义,但均显著高于WKY组(均P<0.01);给药后法舒地尔各组大鼠SBP水平明显低于同一时段SHR组(均P<0.05),但仍未达XBDP组大鼠血压水平(P<0.05);同时随着法舒地尔剂量增加,SHR大鼠SBP下降更明显(P<0.05);WKY组血浆NO浓度明显高于SHR组(P<0.01),血浆ET-1浓度明显低于SHR组(P<0.01)。给药8周后,法舒地尔各组血浆NO浓度明显高于SHR组(均P<0.05),而血浆ET-1浓度明显低于SHR组(P<0.05);而XBDP组同SHR组比较差异无统计学意义。与SHR组相比,法舒地尔各组大鼠主动脉、心肌组织中Rho激酶mRNA的表达量明显降低(均P<0.05),且随剂量增加表达进一步下降;XBDP组变化不明显。结论:Rho激酶抑制剂能够降低SHR的SBP,其机制可能与下调主动脉、心肌组织中Rho激酶mRNA的表达、降低血浆ET-1水平及增加血浆NO水平有关。Objective：To investigate the effects of Rho-kinase inhibitor on blood pressure in spontaneously hypertensive rats（SHR）.Method：Thirty SHR were randomly divided into five groups：SHR control group（SHR group,n=6）,5mg/kg fasudil group（SHRL group,n=6）,10mg/kg fasudil group （SHRM group,n=6）, 20mg/kg fasudil group（SHRH group,n=6）and nifedipine group（XBDP group,10mg/kg,n=6）.Six male Wistar-Kyoto rats were selected as normal control group（WKY group）.Systolic blood pressure（SBP）was meas- ured before and after treatment every 2 weeks.Plasma NO and ET-1 were measured.The expression of Rho kinase mRNA in aorta and heart in the six groups were detected by RT-PCR.Result：SBP in all SHR groups was much higher than that in WKY group before experiment（P〈0.01）.Compared with SHR group,SBP significant- ly decreased in the three fasudil groups（all P〈0.05）.Compared with SHRL group,the level of SBP in SHRH group was significantly decreased （P〈0.05）.The plasma level of NO in WKY group was significantly higher than that in SHR group（P〈0.01）,and the plasma level of ET-1was significantly lower than that in SHR group （P〈0.01）.After 8weeks,plasma NO levels in the three fasudil groups were markedly higher than that in SHR group（all P〈0.05）,while plasma ET-1levels were markedly lower than that in SHR group（P〈0.01）.But the plasma NO and ET-1levels were not different between SHR group and XBDP group.Compared with SHR group, the expressions of Rho kinase mRNA in aorta and heart were significantly decreased in three fasudil groups（all P〈0.05）,but were not decreased in XBDP group.Conclusion：Rho kinase inhibitor significantly down-regulated the expression of Rho kinase gene in aorta and heart of SHR,and increased plasma NO level and decreased plasma ET-1level in SHR,which might be,at least partly,the mechanism of the favorable effects of Rho kinase inhibitor in regulating blood pressure.

关 键 词：高血压 RHO激酶抑制剂 自发性高血压大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]