血管内皮生长因子和内皮素在低氧性肺血管重建中的作用

目的探讨血管内皮生长因子(VEGF)和内皮素(ET)-1在低氧性肺动脉高压(HPH)及其肺血管重建中的作用,并观察钾通道开放剂(pinacidil)对HPH的防治作用及对VEGF和ET-1的影响.方法Wister大鼠46只,随机分为3组,对照组15只,低氧组16只,治疗组15只.缺氧组和治疗组大鼠缺氧氧浓度为(10.0±0.5)%]4周,每天缺氧8h,其中治疗组大鼠于每天缺氧前腹腔注射pinacidil3mg/kg.缺氧4周后测定各组大鼠血清VEGF和血浆ET-1水平、平均肺动脉压(mPAP)、右心室(RV)/左心室(LV)+室间隔(S)]比值及肺小动脉病理及其形态计量学.结果(1)缺氧组大鼠血清VEGF(118.73±55.40)ng/L]和血浆ET-1(221.2±56.2)ng/L]水平明显高于对照组(P＜0.01);缺氧组较对照组mPAP升高,RV/(LV+S)比值增高,肺小动脉血管壁显著增厚,管腔明显狭窄.(2)治疗组大鼠血清VEGF(78.20±16.45)ng/L]和血浆ET-1(181.6±30.5)ng/L]水平明显低于缺氧组(P＜0.01);治疗组较缺氧组mPAP下降(P＜0.01),肺小动脉血管壁增厚、管腔狭窄等明显减轻,但治疗组上述各指标仍未完全恢复到对照组水平.结论VEGF和ET-1在HPH及其肺血管重建中发挥重要作用,钾通道开放剂对HPH及其肺血管重建具有一定的逆转作用.

The roles of vascular endothellial growth factor and endothelin-1 on pulmonary vascular remodelling in rats with hypoxia-induced pulmonary hypertension

OBJECTIVE: To investigate the roles of the vascular endothelial growth factor(VEGF) and endothelin-1(ET-1) in pulmonary vascular remodelling in rats with hypoxia-induced pulmonary hypertension(HPH) and the effect of pinacidil on VEGF and ET-1 in rats with HPH. METHOD: 46 male Wister rats were divided into three groups i.e. control group, hypoxic group and treated group (hypoxic rats treated with pinacidil for 4 weeks). Rat models with chronic HPH were established by chronic hypobaric hypoxia (10.0 +/- 0.5)% O2, 4 weeks]. The levels of VEGF and ET-1 in serum and the mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricle (RV)/left ventricle and septum (LV + S) RV/(LV + S)] were measured and the small pulmonary arterial morphologic changes were observed with morphometric analysis under microscopes in the three groups. RESULTS: (1) The levels of VEGF(118.73 +/- 55.40) ng/L] and ET-1(221.2 +/- 56.2) ng/L] in serum, mPAP (28.4 +/- 2.8) mm Hg, 1 mm Hg = 0.133 kPa] and RV/(LV + S) (0.296 +/- 0.033) were significantly higher in the hypoxic group than those in the control group (P < 0.01). Morphometry showed that the external diameter of the small pulmonary arteries became smaller and the ratio of vascular wall thickness to external diameter (MT%) (25.70 +/- 2.58)% and ratio of vascular wall area to total area (MA%) (75.300 +/- 5.600)% significantly increased in the hypoxic group. (2) The levels of VEGF(78.20 +/- 16.45) ng/L] and ET-1(181.6 +/- 30.5) ng/L] in serum, mPAP(23.3 +/- 2.6) mm Hg], RV/(LV + S) (0.266 +/- 0.037), MT%(22.10 +/- 2.51)% and MA% (66.900 +/- 0.061)% significantly decreased in the treated group. CONCLUSION: VEGF and ET-1 play important roles in the development of HPH and pulmonary vascular remodelling. Pinacidil may partly inhibit the development of HPH and pulmonary vascular remodelling by decreasing VEGF and ET-1.