银杏叶制剂对缺氧性肺动脉高压的影响及其与蛋白激酶C的关系

The effect of ginkgo biloba on hypoxic pulmonary hypertension and the role of protein kinase C

目的 探讨银杏叶制剂对大鼠缺氧性肺动脉高压的影响及作用机制与蛋白激酶C(PKC)的关系。方法 (1)Wistar大鼠随机分为正常对照 (C)组、缺氧 (H)组及银杏叶治疗 (GB +H)组(2 0 0mg·kg 1·d 1,灌胃 ) ,每组 7只 ,测其平均体、肺循环动脉压 (mSAP、mPAP)及右心室重 /(左心室重 +室间隔重 ) [RV/(LV +S) ]后 ,再取动物左、右肺外肺动脉 (PA)干 ,观察对 5 0 0nmol/LPKC激动剂phorbol12 ,13 dibutyrate (PDBu)的时间 效应曲线及对 10～ 110 0 0nmol/LPDBu的浓度 效应曲线 ,以衡量PKC的功能状态。 (2 )将 18例肺叶切除患者的肺内肺动脉随机分为PDBu组、PKC抑制剂RO3182 2 0 +PDBu组及银杏苦内酯B(BN5 2 0 2 1) +PDBu组 ,每组 6例 ,作对 1～ 2 5nmol/LPDBu的浓度 效应曲线 ,以衡量PKC的功能状态。结果 (1)动物实验 :H组的mPAP、RV/(LV +S)均分别高于C组及GB +H组 (P均 <0 0 5 ) ,GB +H组的mPAP仍高于C组 (P <0 0 5 )。在离体PA水平 ,H组的PKC功能状态均分别显著高于C组及GB +H组 (P均 <0 0 5 )。 (2 )人体标本实验 :在离体人肺内PA水平 ,PDBu组的PKC功能状态均分别显著高于RO3182 2 0 +PDBu组及BN5 2 0 2 1+PDBu组 (P均 <0 0 5 )。结论 银杏叶制剂有降低慢性缺氧大鼠肺动脉高压、减轻右心室肥厚之?

Objective To elucidate whether the mechanism of relieving hypoxic hypertension by ginkgo biloba involves attenuation of the function of protein kinase C(PKC) signal channel Methods 1 Wistar rats were randomly divided into control(C), hypoxic(H) and ginkgo biloba treatment(GB+H)(200 mg·kg 1 ·d 1 , orally) groups ( n =7) Each rat was first measured mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP) and the ratio of the weight of right ventricle to that of left ventricle plus septum [RV/(LV+S)], then two main pulmonary artery rings were isolated to exposed to PDBu(a specific activator of PKC) to observe the time response curve and the dose response curve in response to 500 nmol/L PDBu and 10～11 000 nmol/L PDBu respectively to evaluate the function of protein kinase C signal channel 2 Intrapulmonary artery rings of human(IARH) from pneumolobectomy were randomly divided into PDBu, RO318220 (inhibitor of PKC)+PDBu and ginkgolide B(BN52021)+PDBu groups( n =6), the IARH of three groups were exposed to 1～25 nmol/L PDBu to achieve dose response curves respectively Results (1) mPAP, RV/(LV+S) of the H group were greater than those of C and GB+H groups respectively ( P <0 05) mPAP of GB+H group was greater than that of C group ( P <0 05) In PA experiments, the function of protein kinase C of H group was higher than those of C and GB+H groups respectively( P <0 05) (2) In IARH experiments, the function of protein kinase C of PDBu group was higher than those of RO318220+PDBu and BN52021+PDBu groups respectively( P <0 05) Conclusions Ginkgo biloba can reduce chronic hypoxic pulmonary hypertension and relieve the hypertrophy of right ventricle, which is partly related to attenuation of the function of PKC signal channel.