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

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

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pinacidil 3mg/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± 5 5 40 )ng/L]和血浆ET 1[(2 2 1 2± 5 6 2 )ng/L]水平明显高于对照组 (P <0 0 1) ;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 2 0± 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 0 1) ;治疗组较缺氧组mPAP下降 (P <0 0 1) ,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 。

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)% O 2,4 weeks]. The levels of VEGF and ET 1 in serum and the mean pulmonary arterial presure (mPAP) and the weight ratio of right ventricle (RV)/left ventricle and septum (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