异丙酚对高血压大鼠胸主动脉内皮型一氧化氮合酶和诱导型一氧化氮合酶表达的影响

摘要

Objective To investigate the effect of propofol on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression in thoracic aorta of hypertensive rats.Methods Healthy SD rats of both sexes weighing 240-280 g were used in this study.Hypertension was induced by subcutaneous deoxycorticosterone 25 mg/kg twice a week for consecutive 7 weeks.Sixty-four hypertensive rats were randomly divided into four groups (n ＝ 16 each):hypertension group (group H),low,medium and high dose propofol group ( groups P1,P2,P3 ).Groups P1,P2 and P3 received infusion of propofol at a rate of 20,30 and 40 mg* kg- 1 · h- 1 for 3 h respectively,while group H received equal volume normal saline instead of propofol.Mean arterial pressure (MAP) was monitored and recorded before,1 h and 3 h after the start of propofol or normal saline infusion.All animals were sacrificed at 3 h of intravenous administration.Blood samples were collected by taking out the eyeballs for determination of serum NO concentrations by nitrate reductase method.The expression of eNOS mRNA,iNOS mBNA was determined by reverse transcription-polymerase chain reaction.The expression of eNOS and iNOS protein was determined by Western blot.Results Compared to group H,MAP was decreased significantly,the serum NO concentrations were increased significantly,the expression of eNOS mRNA and protein in thoracic aorta was up-regulated,and the expression of iNOS mRNA and protein in thoracic aorta was down-regulated in a dose-dependent manner in groups P1,P2 and P3 ( P < 0.05 or 0.01 ).Conclusion Propofol can down-regulate iNOS expression and up-regudate eNOS expression in endothelial cells of thoracic aorta and promote NO release in hypertensive rats,Which is the mechanism of propofol decreasing pressure.%目的 评价异丙酚对高血压大鼠胸主动脉内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)表达的影响.方法 SD大鼠,雌雄各半,体重240～ 280 g,采用皮下注射去氧皮质酮的方法制备高血压模型,采用随机数字表法,将64只造模成功的大鼠随机分为4组(n＝16):高血压组(H组)、小剂量异丙酚组(P1组)、中剂量异丙酚组(P2组)和大剂量异丙酚组(P3组).P1组、P2组和P3组分别静脉输注异丙酚20、30、40 mg·kg-1·h-13 h,H组给予等容量生理盐水.分别于给药前、给药1h、3h时记录平均动脉压(MAP).给药3h时处死大鼠,摘眼球法采集血样,硝酸还原酶法测定血清一氧化氮(N0)浓度,取胸主动脉,采用RT-PCR和Western blot法测定eNOS mRNA、iNOS mRNA及其蛋白表达水平.结果 与H组比较,P1组、P2组和P3组给药3h时MAP降低,血清NO浓度升高,主动脉eNOS mRNA及其蛋白表达上调,主动脉iNOS mRNA及其蛋白表达下调,且呈剂量依赖性(P<0.05或0.01).结论 异丙酚降低高血压大鼠血压的机制与下调iNOS表达,上调血管内皮细胞eNOS表达,促进NO释放有关.