比索洛尔对一氧化氮和内皮型一氧化氮合酶昼夜节律的影响  

Effect of bisoprolol on circadian rhythm of nitric oxide and endothelial nitric oxide synthase

作　　者：于立杰[1,2] 郭艺芳[1] 贡玉苗[1] 袁静[1] 张海燕[1] 袁艳敏[1] 赵晓云[1] 国雪[1] 张冬惠[1] 

机构地区：[1]河北省人民医院老年心脏科,河北省老年医学重点实验室,河北石家庄050051 [2]河北省衡水市哈励逊国际和平医院

出　　处：《中华高血压杂志》2012年第6期518-522,共5页Chinese Journal of Hypertension

基　　金：河北省自然科学基金资助项目(C2007000951)

摘　　要：目的探讨比索洛尔对大鼠一氧化氮和内皮型一氧化氮合酶(eNOS)及心肌组织eNOSmRNA表达水平昼夜节律的影响。方法健康雄性SD大鼠128只,体质量250～300g,随机分为4组:7:00灌药组(早灌药组)、19:00灌药组(晚灌药组)、7:00对照组(早对照组)、19:00对照组(晚对照组),每组32只。每日早灌药组与晚灌药组均给予比索洛尔3mg/kg灌服,两对照组分别于7:00与19:00给予相同剂量的安慰剂灌服。4周后,分别于同日内不同时间点(2:00,8:00,14:00,20:00)处死4大组大鼠中各8只大鼠,留取血清和心肌组织。分别采用比色法和硝酸还原法、逆转录多聚酶链反应法检测血和心肌组织中eNOS、一氧化氮的含量或活性以及eNOSmRNA的表达水平。结果两灌药组之间、两对照组之间血清及组织一氧化氮、eNOS含量或表达差异无统计学意义(均P>0.05),但灌药组和对照组之间血清及组织一氧化氮、eNOS含量或表达差异有统计学意义(均P<0.05),灌药组的一氧化氮、eNOS含量明显升高,eNOSmRNA的表达增强(P<0.05)。各组血清及组织一氧化氮、eNOS含量或表达均存在昼夜节律,灌药组部分节律振幅、峰值改变。灌药组和对照组各组的组织eNOSmRNA存在典型昼夜节律,节律振幅无差异。早、晚灌服比索洛尔对于一氧化氮、eNOS以及eNOSmRNA昼夜节律的影响有所不同。结论比索洛尔升高血清及组织一氧化氮、eNOS的含量,促进组织eNOSmRNA的表达。比索洛尔可对内皮源性血管活性物质的时间生物学特征产生影响,用药时间不同,对各参数的影响亦有所不同。Objective To investigate the effect of bisoprolol on circadian rhythm of nitric oxide （NO）, endothelial nitric oxide synthase （eNOS）, and eNOS mRNA in heart tissue. Methods One hundred and twenty eight male SD rats weighted 250-300 g were randomly divided into four groups. The rats in treatment groups were given orally 3 mg/kg bisoprolol every day and those in the control groups were given the same dosage of placebo at 7：00 and 19：00, respectively. After 4 weeks feeding, eight rats in each group were euthanized at different times in one day （2：00, 8：00, 14：00, 20：00） and the blood and myocardial tissues were collected. Colorimetric method and acid reductase method were used to measure the content and activity of NO, eNOS in blood and myocardial tissues. Reverse transcription PCR method was introduced to measure the eNOS mRNA expression in myocardial tissues. Results The serum or tissue content of NO and the activities of eNOS had no significant difference between the con- trol groups and between the treatment groups （P〉0.05）. There was significant difference between the control groups and treatment groups （P〈0.05）. The circadian rhythm of serum or tissue NO and eNOS existed and the amplitudes were different between the control groups and treatment groups. The tissue eNOS mRNA expressions of each group also had significant difference （P〈0.05） and possess the characteristic of circadian rhythm and their amplitudes were the same. Conclusion Bisoprolol might have effect on the content or activity of NO, eNOS in blood and myocardial tissues, and have effect on the expression of myocardial tissue eNOS mRNA.

关 键 词：一氧化氮 内皮型一氧化氮合酶 比索洛尔 血压 昼夜节律 

分 类 号：R544.1[医药卫生—心血管疾病]