川芎嗪对大鼠缺血再灌注心肌预适应性保护与一氧化氮的关系

Protective effect of pharmacological preconditioning of ligustrazine on myocardial ischemical reperfusion injury in rats in relation to nitrogen monoxide

目的:观察川芎嗪对大鼠心肌缺血再灌注损伤的保护作用及其与一氧化氮的关系。方法:实验于2004-06/2005-01在南阳医学高等专科学校药理学实验室完成。选择Wistar大鼠60只,随机分为4组,即空白对照组、模型对照组、川芎嗪组及特异性一氧化氮合成抑制剂亚甲蓝+川芎嗪组,各组均15只。川芎嗪组给予川芎嗪注射液25mg/kg;亚甲蓝+川芎嗪组在川芎嗪组基础上给予亚甲蓝2mg。对各组大鼠进行麻醉后,除正常对照组冠脉左室支下穿线不结扎外,其余各组均结扎大鼠冠脉左室支。结扎30min后,再灌60min诱发心律失常,测定大鼠心电功能及一氧化氮合酶、和一氧化氮含量。亚甲蓝于结扎冠脉左室支前20min输入,川芎嗪则10min后输入。结果:纳入60只大鼠,全部进入结果分析,无脱失。各组大鼠心肌一氧化氮含量及一氧化氮合酶活性比较:模型对照组大鼠再灌注时心肌原生型一氧化氮合酶及总一氧化氮合酶活性显著低于空白对照组(P<0.01),一氧化氮产生减少(P<0.05～0.01)。川芎嗪组缺血期间一氧化氮水平显著高于模型对照组和亚甲蓝+川芎嗪组(P<0.01),心肌原生型一氧化氮合酶及总一氧化氮合酶活性显著高于模型对照组和亚甲蓝+川芎嗪组(P<0.05～0.01)。结论:川芎嗪可以提高缺血再灌注大鼠心肌一氧化氮合酶活性和一氧化氮水平,应用特异性一氧化氮合成抑制剂亚甲蓝可降低大鼠心肌一氧化氮合酶活性和一氧化氮水平。川芎嗪可能通过调节一氧化氮合酶活性,维持正常一氧化氮水平对缺血再灌注心肌损伤大鼠起药理预适应保护作用。

AIM To observe the protective effect of ligustrazine on myocardial ischemical reperfusion injury in rats and its relationship with nitrogen monoxide. METHODS： The experiment was carried out in the Stuff Room of Pharmacology, Nanyang Medical College from June 2004 to January 2005. Sixty Wistar rats were randomly divided into 4 groups： Blank control group, model control group, ligustrazine group and specific nitrogen monoxide synthetic inhibitor methylene blue ＋ligustrazine group with 15 rats in each group. Rats in the ligustrazine group were administrated with 25 mg/kg ligustrazine; Rats in the methylene blue ＋ ligustrazine group received 2 mg methylene blue at the basis of 25 mg/kg ligustrasine. All rats received coronary artery ligation of left ventricle branch after anesthesia except rats in the normal control group. 30 mins after ligation, arrhythmlas was evoked with 60-min-perfusion, then the electrocardio-function and contents of nitricoxide synthase （NOS） and nitrogen monoxide were assayed. Methylene blue was input 20 mins before the coronary artery ligation of left ventricle branch, 10 mins after that ligustrazine was input. RESULTS： Sixty included rats were involved in the analysis of results, no subject withdrew from the experiment. Comparison of contents of nitrogen monoxide and NOS activity in myocardium of rats among groups： They were significantly lower in the model control group than those in the blank control group （P〈0.01）, level of nitrogen monoxide decreased （P〈0.05-0.01 ）. Level of nitrogen monoxide in ischemia rats of the lignstrazine group was significantly higher than that in the model control group and methylene blue＋ligustrazine group （P 〈 0.01）, and myocardial constitutive NOS and total NOS activity in the ligustrazine group were obviously higher than those in the model control group and methylene blue＋lignstrazine group （P 〈 0.05-0.01 ）. CONCLUSION： Ligustrazine can increase NOS activity and elevate the level of nitrogen monoxide of isehemia reperfusion myacardium in rats, methylene blue can reduce the NOS activity and level of nitrogen monoxide. Lignstrasine can maintain the level of nitrogen monoxide by adjusting the activity of NOS, and has a protective effect of pharmacological precomlitiraling on myocardial ischemical reperfusion injury in rats.