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

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

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 [RV/(LV +S) ]。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PMA 0 5 μmol/L对肺动脉环的时间 -效应曲线以及NF -κB抑制剂PDTC 0 - 10 0 0 μmol/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 10 μmol/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t1/ 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 0 5 )。PMA 0 5 μmol/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 0 5 ) ;低氧组t1/ 2 小于常氧组 (P <0 0 5 ) ;低氧组T大于常氧组 (P <0 0 5 )。PDTC 0 - 10 0 μmol/L血管环相对张力低氧组均高于常氧组 (P<0 0 5 ) ;大于 5 0 0 μmol/L两组血管张力均下降 (P <0 0 5 )。 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?

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 ( P_0 ) setting at 100%,and the relative responseness tensions to PMA and PDTC were derived by dividing by the counts in P_0. 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 μmol/L,the relative 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 μmol/L ( P <0.05);the relative tensions of two group significantly decreased beyond PDTC of 500 μmol/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.