尼可地尔对大鼠低氧性肺高压的影响

Effects of nicorandil on hypoxic pulmonary hypertension in rats

目的:探讨线粒体ATP敏感性钾通道开放剂(mitoKATPCO)尼可地尔(nicorandil)对大鼠低氧性肺动脉高压的影响。方法:将40只大鼠随机分成对照组(C组)、低氧组(H组)、低氧+尼可地尔组(N组)与低氧+尼可地尔+5-羟基葵酸盐组(HD组),后3组置于常压低氧仓内,每周6 d,每天8 h,持续4周后测定各组大鼠平均肺动脉压(mPAP),右心肥厚指数RV/(V+S),HE染色观察肺小动脉血管壁的病理变化并检测增殖相关抗原(PCNA)。结果:慢性缺氧可诱导大鼠mPAP及RV/(LV+S)升高,大鼠肺小血管增厚重构,PCNA表达增加,尼可地尔可显著抑制上述变化,且该效应可被线粒体KATP(mitoKATP)通道特异性阻断剂5-羟基葵酸盐阻断。结论:尼可地尔通过开放mitoKATP通道降低肺动脉压,拮抗右心肥厚,并抑制肺血管增殖重构,治疗低氧性肺高压。

Objective：To investigate the effects of nicorandil,a mitochondria adenosine triphosphate（ATP）-sensitive potassium channel opener（mitoKATPCO） on the development of hypoxic pulmonary hypertension（HPH） in rats.Methods： Forty rats were randomly divided into 4 groups（control group and three hypoxic groups including the simple hypoxic,nicorandil treatment as well as the nicorandil＋5-hydroxydecanoate treatment group） with 10 rats each.The latter three hypoxic groups were placed into normobaric hypoxic chamber（8 h/day and 6 days/week）.After 4 weeks,the mean pulmonary arterial pressure（mPAP）,right ventricle/left ventricle and septum[RV/（LV＋S）] were measured and the morphologic changes of small pulmonary arterial were detected by microscopes after hematoxylin-eosin staining.Western blot was performed to analyze the protein expression of proliferating cell nuclear antigen（PCNA）.Results： Hypoxia alone significantly increased the mPAP,RV/（LV＋S） as well as the protein expression of PCNA,the morphologic changes also indicated the significant proliferation and remodeling of the small pulmonary artery in the hypoxic group.The treatment with nicorandil significantly antagonized these changes,and the beneficial effects of nicorandil could be blocked by 5-HD.Conclusion： Nicorandil can significantly reduce the pulmonary artery pressure,antagonize the right ventricular hypertrophy as well as the proliferation and remodeling of the small pulmonary artery through activating the mitoKATP channel.It is a promising candidate for the treatment of HPH.