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.doc

???? 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 ???? ????　【摘要】　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(200 mg.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500 nmol/L PKC激动剂phorbol 12，13-dibutyrate (PDBu)的时间-效应曲线及对10～11 000 nmol/L PDBu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RO318220+PDBu组及银杏苦内酯B（BN52021）+PDBu组，每组6例，作对1～25 nmol/L PDBu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0.05)，GB+H组的mPAP仍高于C组(P0.05)。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0.05)。(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RO318220+PDBu组及BN52021+PDBu组（P均0.05)。结论　银杏叶制剂有降低慢性缺氧大鼠肺动脉高压、减轻右心室肥厚之效，其作用机制至少部分与抑制PKC通道的功能有关。　　【关键词】　银杏叶；　蛋白激酶C；　高血压，肺性 The effect of ginkgo biloba on hypoxic pulmonary hypertension and the role of protein kinase C YANG Hui， XU Yongjian， ZHANG Zhenxiang.(Respiratory Department， Tongji Hospital， Tongji Medical University， Wuhan 430030，China) 　　【Abstract】　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