摘要目的 目前研究发现肺静脉参与低氧性肺动脉高压疾病的发生发展.低氧造成的肺血管收缩反应和肺血管重塑不仅发生于肺动脉,而且包括肺静脉.然而慢性低氧导致肺静脉重塑的机制仍不清楚,故本文主要观察慢性低氧对大鼠肺静脉重塑的影响,并研究其分子机制.方法 SD大鼠20只,体重200 ～ 250 g,按随机数字表法分为常氧组和慢性低氧组(CH组),每组10只,CH组放入全自动缺氧箱饲养,21 d后测量右心室收缩压(right ventricular systolic pressure,RVSP)及平均右心室压(mean right ventricular pressure,mRVP);解剖心脏计算右心室肥厚指数[RV/(LV+S)];取右肺组织做VG染色并测量小静脉血管管腔面积,计算血管中膜厚度百分比(WT％);Western blot法检测远端肺静脉平滑肌组织和原代培养的大鼠远端肺静脉平滑肌细胞(PVSMCs)中过氧化物酶体增殖物受体(PPARγ)蛋白的表达.结果 与常氧组[(27.06 ±2.10)、(12.58 ±0.82) mmHg(1 mmHg=0.133kPa)]比较,CH组大鼠RVSP和mRVP均明显升高[(50.46±9.51)、(21.66±1.85) mmHg,P＜0.05];CH组右心室肥厚指数(0.56±0.05)比常氧组(0.36±0.04)明显升高(P＜0.05);CH组静脉血管腔占血管区域的比值为(48.62±13.61)％,与常氧组(66.16±8.72)％相比显著降低(P＜0.05),而CH组静脉WT％ (16.43±5.08)％与NC(7.23 ±0.71)％相比显著增加(P＜0.05);此外CH组大鼠肺静脉平滑肌组织和细胞PPARγ蛋白相对常氧组的表达量分别为(52.95±3.83)％和(59.38±17.12)％,差异有统计学意义(P＜0.05).结论 CHPH大鼠模型RVSP、mRVP、右心室肥厚指数均升高,同时伴有肺小静脉重塑,其机制可能与低氧诱导静脉PPARγ蛋白表达降低有关.

abstractsObjective To investigate the effect of chronic hypoxia on pulmonary vein remodeling in rats and its underlying molecular mechanism.Methods Totally 20 adult SD rats (200-250 g),in accordance with a random number table,were divided into normoxia control group (NC) and chronic hypoxia group (CH).CH group rats were put into automatic hypoxia box for 21 days.After that,RVSP,mRVP and RV/(LV + S) were measured;Lung histopathological sections were prepared.The lumen area,ratio of wall thickness to radius of pulmonary veins were gauged by using the Image Pro Plus 6.0 software.Primary PVSMCs were cultured in hypoxia (4％ O2) or normoxia (21％ O2) for 60 hours respectively before extracted total protein for Western blotting analysis.PPARγprotein expression in rat pulmonary vein smooth muscle and pulmonary vein smooth muscle cells was detected by Western blot.Results Compared with NC group[(27.06±2.10),(12.58 ±0.82)mmHg(1 mmHg =0.133 kPa)],the RVSP and mRVP in CH group [(50.46 ± 9.51),(21.66 ± 1.85) mmHg] were significantly increased (P ＜ 0.05).The RV/(LV + S) of CH group was (0.56 ± 0.05),markedly higher than that of NC group (0.36 ± 0.04,P ＜ 0.05).The luminal area/total area of vein in CH group decreased to(48.62 ± 13.61)％ compared with that in NC group (66.16 ± 8.72) ％ (P ＜ 0.05).The wall thickness/venous radius (WT％) of CH group increased from (7.23 ± 0.71) ％ (NC) to(16.43 ± 5.08) ％ (P ＜ 0.05).The level of PPARγ protein in pulmonary vein smooth muscle of CH group was (52.95 ± 3.83) ％,lower than that of NC (100 ± 0) ％ (P ＜0.05).PPARγ protein in pulmonary vein smooth muscle cells cultured in vitro in hypoxia was (59.38 ± 17.12) ％,lower than that cultured in normoxia (100 ± 0) ％ (P ＜ 0.05).Conclusion Hypoxia induced increase of RVSP,mRVP,RV/(LV + S),and accompanied with pulmonary venous remodeling.The underlying mechanism of the vein change may related to down-regulated expression of PPARγ.