L-精氨酸对低氧性肺动脉高压大鼠离体肺动脉环蛋白激酶C通道的影响  

The effect of L-arginine on protein kinase C of isolated pulmonary arterial rings from rats with hypoxia-induced pulmonary hypertension

作　　者：杨慧[1] 徐永健[1] 张珍祥[1] 

机构地区：[1]同济医科大学附属同济医院呼吸内科,湖北武汉430030

出　　处：《中国病理生理杂志》2001年第2期108-111,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金 (No .3 9770 3 4 1) ;国家教委留学回国人员科研启动基金资助 (No.974 3 6)

摘　　要：目的 :探讨L -精氨酸 (L -Arg)降低低氧性肺动脉高压 (HPAH)的机制是否涉及抑制慢性低氧时蛋白激酶C(PKC)通道的激活。方法 :2 1只雄性Wistar大鼠随机分为生理盐水对照、低氧及L -Arg治疗组 ( 5 0 0mg·kg-1·d-1,ip) ,处理两周。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 ,各动物再取左、右肺外肺动脉干 ,观察在离体情况下 :( 1)对 5 0 0nmol/LPKC激动剂PDBu的最大收缩反应 (P1)、达1/ 2最大张力 (P1/ 2 )时所需时间 (t1/ 2 )、峰值持续时间 (T)及在各时点 ( 2、4、8、12、2 0、4 0、60、80min)时的张力值 (张力均表示为占同一血管对 5 μmol/L盐酸苯肾上腺素最大收缩反应P0 的百分比 ,即P0 %)。 ( 2 )描绘对 10 - 110 0 0nmol/LPDBu的浓度 -效应曲线 ,计算半效浓度EC50 。结果 :生理盐水对照组及L -Arg治疗组的mPAP、RV/ (LV +S)、P1、T及在 2、4、8、2 0min时的张力值均分别低于低氧组 (均P <0 .0 5 ) ,t1/ 2 及EC50 则均分别高于低氧组 (均P <0 .0 5 )。结论 :慢性低氧时PKC通道功能状态上调 ,参与肺血管反应性增高的形成 ;L -Arg可抑制PKC通道的激活 ,可能是其降低肺动脉高压、减轻右心室肥厚的机制之一。AIM: To elucidate whether the mechanism that L-arginine can relieve hypoxia pulmonary hypertension involves inhibition of the activity of protein kinase C(PKC). METHODS: Twenty-one male Wistar rats were randomly divided into NS control, hypoxia and L-arginine(500 mg·kg -1 ·d -1 , ip) treatment groups. After two-weeks treatment, mean pulmonary artery pressure (mPAP), mean systematic artery pressure (mSAP) and the ratio of the weight of right ventricle to that of left ventricle plus septum were measured, then two pulmonary arterial rings were isolated to be exposed to PDBu(a specific activator of PKC ) and observed: (1) The maximal response (P 1) to 500 nmol/L PDBu, the time required to achieve a half-maximal response to 500 nmol/L PDBu (t 1/2 ), the time during which the maximal response to 500 nmol/L PDBu maintained (T) and the isometric responses at different times (2, 4, 8, 12, 20, 40, 60, 80 min). The isometric response was represented as the percentage of the maximal response (P 0) of the same arterial ring to 5μmol/L phenylephrine hydrochloride (P 0%). (2) Dose-response curve in response to PDBu (10-11 000 nmol/L) and the dose producing a half-maximal response in the curve (EC 50 ). RESULTS: mPAP, RV/(LV+S), P 1, T and the isometric responses at 2, 4, 8, 20 min of NS control and L-arginine treatment groups were lower than those of hypoxic group respectively (P<0.05), while t 1/2 and EC 50 were all greater than those of hypoxic group respectively (P<0.05). CONCLUSION: The activity of PKC was augmented when rats were exposed to two-weeks normobaric hypoxia, which resulted in the increased reactivity of the isolated pulmonary arterial rings. L-arginine can inhibit the activation of PKC, which is likely part of the mechanism by which L-arginine can reduce mPAP and relieve the hypertrophy of right ventricle.

关 键 词：精氨酸 蛋白激酶C 高血压 肺性 肺动脉 

分 类 号：R543.2[医药卫生—心血管疾病]