腺苷对猪缺血再灌注心肌组织一氧化氮合酶同工酶的影响

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目的:评价缺血再灌注后一氧化氮合酶(NOS)同功酶的变化以及腺苷对其的影响。方法:中华小型猪24只,随机分成缺血再灌注模型组、腺苷组和假手术组,每组8只。冠状动脉结扎180min,松解60min制备缺血再灌注模型。检测缺血前5min,缺血后5,180min和再灌注后5,60min血NO的含量并观察正常、缺血和无再流区心肌组织内NOS同功酶及其mRNA的表达。结果:(1)与缺血前比较,缺血后180min、再灌注后5min和60min的血NO水平均显著降低(均P<0.01),然而再灌注后5min和60min的血NO水平比缺血后180min有显著升高(均P<0.01)。而腺苷组缺血后180min血NO降低幅度显著低于模型组(P<0.05)。再灌注后5min和60min的血NO水平与缺血后180min相比无显著变化(P>0.05)。(2)与正常区心肌组织相比较,模型组和腺苷组一样,缺血区和无再流区心肌组织中结构型一氧化氮合酶(cNOS)活性及其mRNA表达均显著减低,诱导型一氧化氮合酶(iNOS)活性及其mRNA表达均显著升高(均P<0.01),而无再流区cNOS活性及其mRNA表达减低和iNOS活性及其mRNA表达的升高比缺血区均更显著(P<0.05或P<0.01)。与模型组相比较,腺苷组仅缺血区心肌组织中iNOS活性及其mRNA表达显著降低,cNOS活性及其mRNA表达显著升高(P<0.05或P<0.01)。结论:NOS的变化可能是无再流发生的重要机制之一。腺苷可能通过升高cNOS活性,降低iNOS活性起到了减少无再流的作用。 Objective: To evaluate the changes of nitric oxide synthase (NOS) isoenzyme and the effect of adenosine on it after ischemia-reperfusion. Methods: Twenty-four Chinese miniature pigs were randomly divided into ischemia-reperfusion model group, adenosine group and sham operation group, with 8 rats in each group. Coronary ligation 180min, release 60min ischemia-reperfusion model. The levels of NO were measured at 5 min before ischemia, 5,180 min after ischemia and 5,60 min after reperfusion. The expression of NOS isoenzyme and its mRNA in normal, ischemic and non-reflow myocardium were observed. Results: (1) Compared with preischemia, the level of blood NO was significantly decreased at 180 min after ischemia, at 5 min and 60 min after reperfusion (all P <0.01), however, the levels of NO at 5 min and 60 min after reperfusion were significantly lower than those at ischemia After 180min were significantly increased (all P <0.01). In adenosine group, the decrease of blood NO level 180 min after ischemia was significantly lower than that of model group (P <0.05). The level of blood NO at 5 min and 60 min after reperfusion had no significant change compared with 180 min after ischemia (P> 0.05). (2) Compared with the normal myocardium, the activity of nitric oxide synthase (cNOS) and the mRNA expression of cNOS in ischemic and non-reflow myocardium were significantly decreased in model group and adenosine group (All P <0.01), but no cNOS activity and mRNA expression, iNOS activity and mRNA expression were higher than those of ischemia Area were more significant (P <0.05 or P <0.01). Compared with the model group, only the iNOS activity and mRNA expression in the ischemic myocardium of adenosine group were significantly decreased and the cNOS activity and mRNA expression were significantly increased (P <0.05 or P <0.01). Conclusion: The changes of NOS may be one of the important mechanisms of no-reflow. Adenosine may reduce the effect of no reflow by increasing cNOS activity and decreasing iNOS activity.
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