贝前列素钠对低氧性肺动脉高压大鼠的作用及对肺动脉平滑肌氧敏感性K_V通道表达的影响

Effect of beraprost sodium on HPH rats and expression of oxygen-sensitive K_V channels in pulmonary artery smooth muscle

目的探讨贝前列素钠(BPS)对低氧性肺动脉高压(HPH)大鼠的疗效,及其对肺动脉平滑肌氧敏感性KV通道表达的影响。方法采用在低压低氧舱内每日饲养8h的方法建立HPH大鼠模型;BPS干预组每日给予BPS灌胃[300μg/(kg·d)],对照组和模型组给予生理盐水灌胃;4周后测定平均肺动脉压力(mPAP),计算右心肥厚指数(RVHI),肺组织切片HE染色评价肺动脉壁增厚程度,Real-time PCR和Western blot检测肺小动脉平滑肌KV1.2、KV1.5、KV2.1mRNA和蛋白表达水平。结果连续4周低压低氧成功诱导HPH大鼠模型;与模型组相比,BPS干预后mPAP和RVHI降低[mPAP:(13.48±2.18)mmHg vs.(23.87±2.23)mmHg vs.(17.09±1.20)mmHg;RVHI:0.28±0.02 vs.0.46±0.03 vs.0.36±0.04;P<0.05];肺小动脉重构改善(中膜面积百分比:35.72±6.58 vs.68.52±5.64 vs.46.58±8.43,P<0.05),肺动脉平滑肌KV1.2、KV1.5、KV2.1mRNA和蛋白表达水平升高(蛋白相对表达量:KV1.2,0.78±0.10 vs.0.15±0.03 vs.0.57±0.13;KV1.5,0.61±0.10 vs.0.31±0.05 vs.0.59±0.13;KV2.1,0.29±0.05 vs.0.10±0.02 vs.0.28±0.07;P<0.05)。结论 BPS可改善HPH大鼠的肺动脉高压,并上调肺动脉平滑肌KV1.2、KV1.5、KV2.1的表达。

Objective To explore the effect of beraprost sodium （BPS） on hypoxia-induced pulmonary artery hypertension （HPH） in rats and the expression of oxygen-sensitive Kv channels in pulmonary artery smooth muscle （PASM）. Methods The HPH model of rats was established by exposing rats to Sow-pressure and low-oxygen cabin which was auto-modulated for 8h every day. Rats in the BPS group were given an intragastric administration of BPS [300μg/（kg @ d）], while those in the control group and HPH group were given an intragastric administration of 3 ml/kg of 0.9% saline. After 4 weeks, the mean pulmonary artery pressure （mPAP） was measured and right heart ventricle hypertrophy index （RVHI） was calculated; pulmonary artery remodeling was evaluated by HE staining; the expressions of Kv 1.2, Kv 1.5 and Kv2.1 in the pulmonary artery were detected by Real-time PCR and Western blot. Results The HPH model was successfully established in rats exposed to chronic hypoxia for 4 weeks. Compared with those in HPH group, mPAP, RVHI and pulmonary artery remodeling were decreased in BPS group [mPAP： （13.48±2.18）mmHg vs. （23.87±2.23）mmHg vs. （17.09±l.20）mmHg; RVHI： 0.28±0.02 vs. 0.46 ±0.03 vs. 0.36±0.04; % area of medial smooth muscle： 35.72±6.58 vs. 68.52±5.64 vs. 46.58±8.43; P〈0.05], and the mRNA and protein expressions of Kv 1.2, Kv 1.5 and Kv 2.1 were increased （relative protein expressionlevel： Kvl.2, 0.78±0.10 vs. 0.15±0.03 vs. 0.57±0.13;Kv1.5, 0.62±0.10 vs. 0.31±0,05 vs. 0.59±0.13; Kv2.1, 0.29±0.05 vs. 0. 10±0.02 vs. 0.28±0.07; P（0.05）. Conclusion BPS can improve pulmonary arterial hypertension induced by hypoxia, and upregulate the decreased mRNA and protein expressions of Kv1. 2, Kv 1.5 and Kv 2.1 in pulmonary artery.