核因子-κB抑制剂在蛋白激酶C对低氧性肺动脉高压大鼠肺动脉环反应性影响中的作用

目的:探讨核因子-κB抑制剂在蛋白激酶C对低氧性肺动脉高压大鼠离体肺动脉环反应性影响中的作用。方法:复制低氧性肺动脉高压大鼠模型,测定肺动脉平均压(mPAP)、右心室重/(左心室+室间隔)重。取低氧模型组和常氧组大鼠的去内皮肺动脉环,观察PKC激活剂PMA0.5μmol/L对肺动脉环的时间-效应曲线以及NF-κB抑制剂PDTC0-1000μmol/L时对PMA诱导肺动脉环反应性改变的浓度-效应曲线。以血管环对10μmol/L盐酸苯肾上腺素的最大反应值为P₀,对PMA和PDTC的反应值以占P₀的百分值表示(%P₀),记录达最大反应值一半时对应的时间t_1/2(min)、峰值持续时间T(min)。结果:低氧组的mPAP及RV/(LV+S)均高于常氧组(P<0.05)。PMA0.5μmol/L作用于血管环:低氧组各时点的张力%P₀均高于常氧组(P<0.05);低氧组t_1/2小于常氧组(P<0.05);低氧组T大于常氧组(P<0.05)。PDTC0-100μmol/L血管环相对张力低氧组均高于常氧组(P<0.05);大于500μmol/L两组血管张力均下降(P<0.05)。结论:低氧可导致去内皮肺动脉环对PMA的反应性增强;PDTC呈剂量依赖性地降低去内皮肺动脉环对PMA的反应性。提示肺动脉平滑肌细胞内PKC－NF-κB生物信号转导途径的变化可能参与低氧性肺动脉高压肺血管反应性异常升高的过程。

Effect of nuclear factor kappa B inhibitor on the responsiveness of pulmonary artery rings to protein kinase C in rats with hypoxia-induced pulmonary hypertension

AIM: To investigate the role of nuclear factor kappa B (NF-κB) inhibitor in the responsiveness of isolated pulmonary artery rings to protein kinase C (PKC) in rats with hypoxia-induced pulmonary hypertension. METHODS: The pulmonary artery rings removed endothelium were prepared from model rats with hypoxia-induced pulmonary hypertension and control rats. The effects of PKC activator PMA (0.5 μmol/L) time-response cures and NF-κB inhibitor PDTC (0-1 000 μmol/L) concentration-response cures on pulmonary artery rings were observed. The responsiveness of each ring was tested by applying a maximally effective concentration of phenylephrine (10 μmol/L). Data were calculated as relative ratio by the maximally responseness ( P₀ ) setting at 100%, and the relative responseness tensions to PMA and PDTC were derived by dividing by the counts in P₀. t_1/2 and T show the time achieving half-maximal response and lasting maxima response to 0.5 μmol/L PMA, respectively. RESULTS: mPAP and RV/(LV+S)in hypoxia group were greater than those in control group(P<0.05).For the responseness of the artery rings to PMA of 0.5 mol/L,the relat ive tensions of hypoxia group were significantly higher(P<0.05)as compared with respective controls;mean t_1/2 in hypoxia group was shorter than that in control group(P<0.05).Mean T in hypoxia group was longer than that in control group(P<0.05).For the relative tensions of the artery rings to PDTC and PMA,hypoxia group were higher than those of controls in the range of PDTC 0-100 mol/L(P<0.05);the relative tensions of two group significantly decreased beyond PDTC of 500 mol/L(P<0.05). CONCLUSIONS: The responsiveness of pulmonary artery rings to PMA was increased during hypoxia and decreased to PDTC in concentration-dependent manner. These results further suggest that changes of PKC－NF-κB signaling pathway of pulmonary artery smooth muscle cells may be involved in vasoconstriction of hypoxia-induced pulmonary hypertension.