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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 effects of bisoprolol on the circadian rhythms of nitric oxide, eNOS and eNOS mRNA in myocardium of rats. Methods 128 healthy male SD rats weighing 250-300 g were randomly divided into 4 groups: 7:00 irrigation group (early irrigation group), 19:00 irrigation group (late irrigation group), 7:00 Control group (early control group), 19:00 control group (late control group), 32 in each group. Daily early irrigation group and late irrigation group were given bisoprolol 3mg / kg orally, the two control groups were given the same dose of placebo at 7:00 and 19:00. After 4 weeks, 8 rats in 4 groups were killed at different time points (2: 00,8: 00,14: 00,20: 00 respectively) on the same day, and serum and myocardial tissue were collected. The levels of eNOS, nitric oxide and the content of eNOS mRNA in blood and myocardium were detected by colorimetric method and nitrate reduction method, respectively. Results There was no significant difference in serum nitric oxide, eNOS content or expression between the two control groups (P> 0.05), but there was no significant difference in serum and tissue nitric oxide Nitrogen and eNOS content or expression were significantly different (all P <0.05). The levels of nitric oxide, eNOS and eNOS mRNA were significantly increased (P <0.05). There were circadian rhythms of nitric oxide and eNOS content or expression in serum and tissues of each group, and some rhythm amplitudes and peak changes of perfusion group. There was a typical circadian rhythm of eNOS mRNA in tissue of the perfusion group and control group, but no difference of rhythm amplitude. Effects of early and late administration of bisoprolol on nitric oxide, eNOS, and eNOS mRNA circadian rhythms were different. Conclusion Bisoprolol increased the content of nitric oxide and eNOS in serum and tissue, and promoted the expression of eNOS mRNA in tissues. Bisoprolol can affect the temporal biological characteristics of endothelium-derived vasoactive substances, the medication time is different, the impact on the parameters are also different.