新型K_(ATP)开放剂埃他卡林对低氧性肺动脉高压大鼠血管活性物质的影响  

Effects of iptakalim,a novel KATP opener,on the changes of vasoactive substances in rats with hypoxic pulmonary hypertension

作　　者：宗峰[1] 左祥荣[1] 王慧[1] 吕剑[1] 解卫平[1] 王虹[1] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,江苏省南京市210029

出　　处：《实用老年医学》2010年第3期206-208,共3页Practical Geriatrics

基　　金：国家自然科学基金项目(30871139);江苏省人事厅"六大人才高峰"第五批高层次人才项目(B类);江苏省研究生培养创新工程项目(CX08B_168Z)

摘　　要：目的探讨缺氧对大鼠血管活性物质分泌的影响及新型KATP开放剂埃他卡林(iptakalim,IPT)治疗肺动脉高压的作用机制。方法清洁级SD大鼠30只随机分成对照组、低氧组、IPT组,每组10只。将低氧组与IPT组放入常压低氧舱制备动物模型,采用右心导管测量大鼠肺动脉压,应用放射免疫法等观察血浆一氧化氮(NO)、内皮素-1(ET-1)及前列环素(PGI2)水平的动态变化。结果低氧组大鼠肺动脉平均压显著高于对照组和IPT组(P<0.05);低氧组大鼠血浆ET-1含量升高,NO及PGI2含量降低,与对照组比较差异有统计学意义(P<0.05);IPT能对抗缺氧引起的ET-1含量升高和NO含量降低,与低氧组比较差异有统计学意义(P<0.05);而对缺氧引起的PGI2含量降低则无明显影响。结论 IPT能抑制缺氧引起的ET-1含量升高和NO含量降低,从而改善内皮细胞功能,降低肺动脉平均压。Objective To approach the influence of hypoxia on the secretion of vasoactive substances in rats with pulmonary hypertension and the mechanism of new KATP opener iptakalim in hypoxic pulmonary hypertension（HPH）. Methods Thirty male SD rats were randomly divided into three groups：the control group and the two hypoxic groups consisting of simple hypoxic group,and treatment group（IPT group） with 10 rats each. Rats in hypoxic group and IPT group were placed into a normobaric hypoxia [（10±0.5）% oxygen] chamber. Right heart catheterization was used to measure pulmonary arterial pressure in rats. The plasma levels of NO,ET-1 and PGI2 were observed by radioimmunoassay. Results Mean pulmonary arterial pressure（mPAP） was significantly higher in hypoxic group than that in control group and IPT group （P〈0.05）. The plasma level of ET-1 in hypoxic group was higher than that in control group （P〈0.05）,and the plasma levels of NO and PGI2 in hypoxic group were lower than those in control group （P〈0.05）. IPT could antagonize the increase of ET-1and the decrease of NO induced by hypoxia （P〈0.05）,but had no effects on the levels of PGI2. Conclusions NO,ET-1 and PGI2 are involved in the pathophysiologic process of HPH. Iptakalim could partly reverse the imbalance of these factors and thus decrease the pulmonary artery pressure.

关 键 词：KATP开放剂 埃他卡林 低氧性肺动脉高压 内皮素 

分 类 号：R543.2[医药卫生—心血管疾病]