【作者】 刘晓红；

【导师】 曾秋棠；

【作者基本信息】 华中科技大学 ， 心血管病学， 2005， 博士

【摘要】 第一部分心肌梗死后钾通道Kv9.Ⅹ基因表达水平变化及意义目的研究大鼠心肌梗死后钾通道Kv9.Ⅹ(Kv9.1、Kv9.2、Kv9.3)基因表达水平的改变，并初步探讨此种变化的意义。方法通过结扎大鼠左前降支近端建立心肌梗死大鼠模型，手术后存活大鼠进入心肌梗死组(MI组)(7天组；30天组)。同时，设立相应的假手术组(SH组)。应用半定量RT-PCR方法检测左室心肌(心肌梗死者取非梗死区左室心肌)钾通道Kv9.1、Kv9.2、Kv9.3m RNA量。结果7天组：与假手术组比较，MI组Kv9.1、Kv9.2、Kv9.3m RNA量明显下降(P＜0.05)。30天组：与假手术组比较，MI组Kv9.1、Kv9.2、Kv9.3mRNA的量均极显著下降(P＜0.01)。MI组：30天组与7天组比较，Kv9.1、Kv9.2、Kv9.3mRNA的量显著下降(P＜0.05)。结论心肌梗死后钾通道Kv9.1、Kv9.2、Kv9.3mRNA表达呈时间依赖性下调。第二部分缬沙坦对大鼠心肌梗死后钾通道Kv9.Ⅹ表达变化的影响目的研究缬沙坦对大鼠心肌梗死后钾通道Kv9.Ⅹ(Kv9.1、Kv9.2、Kv9.3)变化的影响。方法通过结扎大鼠左前降支近端建立心肌梗死大鼠模型，手术后存活大鼠随机分入心肌梗死(MI)组(7天组，30天组)和缬沙坦(VAS)组(7天组，30天组：缬沙坦30mg／kg，1次／日)，同时设立相应假手术(SH)组。心肌梗死组和假手术组对应给予等量盐水。应用半定量RT-PCR方法检测非梗死左室心肌钾通道Kv9.1、Kv9.2、Kv9.3 m RNA量。结果与心肌梗死组比较，无论7天或是30天，缬沙坦组钾通道Kv9.1、Kv9.2、Kv9.3m RNA量均明显升高(分别为：P＜0.05；P<0.01)。与假手术组比较，缬沙坦组钾通道Kv9.1、Kv9.2、Kv9.3m RNA量无差异。与假手术组比较，无论7天或是30天，心肌梗死组钾通道Kv9.1、Kv9.2、Kv9.3m RNA量均明显降低(分别为：P＜0.05；P＜0.01)。心肌梗死30天时与7天时比较钾通道Kv9.1、Kv9.2、Kv9.3mRNA量下降(P＜0.05)。结论缬沙坦可以显著逆转心肌梗死后钾通道Kv9.1、Kv9.2、Kv9.3mRNA表达的下调，且这一作用迅速而完全。第三部分美托洛尔对大鼠心肌梗死后钾通道Kv9.Ⅹ基因表达的影响目的研究美托洛尔对心肌梗死后大鼠心室肌钾通道Kv9.Ⅹ(Kv9.1、Kv9.2、Kv9.3)表达的影响。方法通过结扎大鼠左前降支近端建立心肌梗死大鼠模型，手术后存活大鼠随机分入心肌梗死(MI)组(7天、30天)、美托洛尔(Meto)组(7天、30天；美托洛尔8mg／kg／日，2次／日)，同时设立相应假手术(SH)组。应用半定量RT-PCR方法检测左室心肌(梗死者取非梗死心肌)钾通道Kv9.1、Kv9.2、Kv9.3mRNA量。结果与心肌梗死组比较，30天时美托洛尔组钾通道Kv9.1、Kv9.2、Kv9.3mRNA明显升高(P＜0.05)，7天时无差异。与假手术组比较，无论7天或30天，美托洛尔组钾通道Kv9.1、Kv9.2、Kv9.3mRNA均明显降低(均为P＜0.05)。与假手术组比较，无论7天或30天，心肌梗死组钾通道Kv9.1、Kv9.2、Kv9.3mRNA均显著降低(分别为：P＜0.05；P＜0.01)。心肌梗死30天时与7天时比较钾通道Kv9.1、Kv9.2、Kv9.3m RNA量下降(P＜0.05)。美托洛尔组7天与30天比较无差别。结论美托洛尔能够逆转钾通道Kv9.1、Kv9.2、Kv9.3表达的下调，且这一逆转作用是缓慢的。更多还原

【Abstract】 Part IThe changes and its signification of gene expression of potassium channels Kv9.X in post-MI rat heartObjective To study the changes and signification of the expression of potassium channels Kv9.X（ Kv9.1、 Kv9.2、 Kv9.3） mRNA in post-MI rat heart. Methods Using a rat model of MI, induced by the left anterior descending coronary artery （LAD） ligation in female Sprague-Dawley rats, the living rats divided into post-MI group（ 7 days group[n=10]; 30 days group[n=11]）. Accordingly, the sham-operation group （sham-group） was established. Using semi-quantitative reverse transcriptase-polymerase chain reaction （RT-PCR）, we measured Kv9.1、 Kv9.2、Kv9.3mRNA in each group.Results 7 days group: Compared to the sham-group, Kv9.1、 Kv9.2、 Kv9.3mRNA inthe post-MI group remarkably decreases （P<0.05）; 30 days group: compared to thesham-group, Kv9.1、 Kv9.2、 Kv9.3 mRNA in the post-MI group prominently reduces（P<0.01）; post-MI group: compared to the 7 days group, Kv9.1、 Kv9.2、 Kv9.3 mRNA inthe 30 days group remarkably reduces （P<0.05）.Conclusion The expression of potassium channels Kv9.1、 Kv9.2、 Kv9.3 mRNA aftermyocardial infarction exhibits the time-dependent downregulation. Part IIEffects of valsartan on the changes of expression of potassium channels Kv9.X in post-myocardial infarction ratObjective: To study the effects of valsartan on the changes of the expression of potassium channels Kv9.X （Kv9.1、 Kv9.2、 Kv9.3） of left ventricular non-infarcted myocardiums in post-myocardial infarction （post-MI） rats.Methods: Using a rat model of MI, induced by the left anterior descending coronary artery （LAD） ligation in female Sprague-Dawley rats, the living rats randomly divided into post-MI group （ 7 days group[n=10]; 30 days group[n=11]） or valsartan group(7 days group[n=10]; 30 days group[n=10]; valsartan 30mg.kg^-1.day^-1). Accordingly, the sham-operation group （sham-group） was established. Using semi-quantitative reverse transcriptase-polymerase chain reaction （RT-PCR）, we measured Kv9.1、 Kv9.2、 Kv9.3 mRNA in each group.Results: Compared to MI groups, potassium channels Kv9.1、 KV9.2、 Kv9.3 mRNA in the valsartan groups remarkably increases regardless of on 7 days or 30 days （respectively, P<0.05; P<0.01）. There is no difference between the valsartan groups and the sham-groups. Compared to the sham-groups, potassium channels Kv9.1、 Kv9.2、 Kv9.3 mRNA in the MI groups remarkably decreases regardless of on 7 days or 30 days （respectively, P<0.05; P<0.01）. Compared to on 7 days after myocardial infarction,potassium channels Kv9.1、 Kv9.2、 Kv9.3 mRNA remarkably decreases on 30 days（P<0.05）.Conclusion: Valsartan may reverse the downregulation of expression of potassiumchannels Kv9.1、Kv9.2、Kv9.3 mRNA in post-myocardial infarction rat markedly, whichis quick and absolute. Part IIIEffects of metoprolol on the changes of expression of potassium channels Kv9.X in post-myocardial infarction ratObjective: To study the effects of metoprolol on the changes of the expression of potassium channels Kv9.X （Kv9.1、 Kv9.2、 Kv9.3） of left ventricular non-infarcted myocardiums in post-myocardial infarction （post-MI） rats.Methods: Using a rat model of MI, induced by the left anterior descending coronary artery （LAD） ligation in female Sprague-Dawley rats, the living rats randomly divided into post-MI group （7 days group[n=10]; 30 days group[n=11]） or metoprolol group(7 days group[n=10]; 30 days group[n=9]; 8mg.kg^-1.day^-1). Accordingly, the sham-operation group （sham-group） was established. Using semi-quantitative reverse transcriptase-polymerase chain reaction （RT-PCR）, we measured Kv9.1、 Kv9.2、 Kv9.3 mRNA in each group.Results: Compared to MI groups, potassium channels Kv9.1、 Kv9.2、 Kv9.3 mRNA in the metoprolol group remarkably increases on 30 days （P<0.05）. Compared to the sham-groups, potassium channels Kv9.1、 Kv9.2、Kv9.3 mRNA in the metoprolol groups remarkably decreases regardless of on 7 days or 30 days （P<0.05）. Compared to the sham-groups, potassium channels Kv9.1、 Kv9.2、 Kv9.3 mRNA in the MI groups remarkably decreases regardless of on 7 days or 30 days （respectively, P<0.05; P<0.01）.Compared to on 7 days after myocardial infarction, potassium channels Kv9.1 、 Kv9.2、Kv9.3 mRNA remarkably decreases on 30 days （P<0.05）.Conclusion: Metoprolol may reverse the downregulation of expression of potassiumchannels Kv9.1 、 Kv9.2、 Kv9.3mRNA in post-myocardial infarction rats and this reverseeffect is tardo.更多还原