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目的探讨蛋白激酶C(protein kinase C,PKC)对体外被动致敏人气道平滑肌(human airway smooth muscle,HASM)张力的影响。方法行肺叶切除术患者6例,其中肺癌5例,支气管扩张1例,取手术切除的正常支气管组织标本分为哮喘组与对照组,哮喘组支气管组织用哮喘患者的血清致敏,对照组支气管组织用体检健康者的血清致敏。2组采用肌张力试验观察不同浓度组胺和PKC激活剂豆蔻酰佛波醇乙酯(Phorbol 12-myristate 13-acetate,PMA)对HASM张力的影响。2组均给予PMA阻断剂Ro31-8220和钙通道阻断剂硝苯地平,观察其对PMA所致HSAM收缩反应的抑制情况。结果哮喘组1×10-7、1×10-6、1×10-5、1×10-4 mol/L组胺作用的HASM张力((11.6±3.1)、(21.9±4.1)、(40.1±6.2)、(54.1±13.2)mg/mg)均较对照组((6.4±1.3)、(11.3±2.5)、(23.3±4.7)、(34.1±5.7)mg/mg)明显增高(P<0.05),1×10-7、5×10-7、1×10-6、5×10-6 mol/L PMA作用的HASM张力((12.1±2.7)、(30.9±7.0)、(41.2±9.2)、(53.1±12.3)mg/mg)均较对照组((8.6±1.9)、(22.8±4.8)、(30.9±5.4)、(38.3±7.9)mg/mg)明显增高(P<0.05);2组组胺和PMA作用的HASM张力均随浓度增高而增高,呈剂量依赖性;2组PMA所致HSAM的收缩反应均可被Ro31-8220和硝苯地平完全抑制。结论激活PKC可导致HASM张力增高,该效应在体外被动致敏的HASM中表现更明显。
Objective To investigate the effect of protein kinase C (PKC) on the tension of passive sensitized human airway smooth muscle (HASM) in vitro. Methods Six patients underwent lobectomy, including 5 cases of lung cancer and 1 case of bronchiectasis. Normal bronchial tissue samples were divided into asthma group and control group. Bronchial asthma group was sensitized with serum of asthmatic patients. Bronchus of control group Tissue with healthy people sera sensitized. The effects of different concentrations of histamine and PKC activator Phorbol 12-myristate 13-acetate (PMA) on the tension of HASM were observed in two groups by muscle tension test. Both groups were given PMA blocker Ro31-8220 and calcium channel blocker nifedipine to observe the inhibitory effect of PMA-induced contraction of HSAM. Results HASM tension ((11.6 ± 3.1), (21.9 ± 4.1), (40.1 ± 6.2 and 54.1 ± 13.2 mg / mg, respectively, were significantly higher than those in the control group (6.4 ± 1.3, 11.3 ± 2.5, 23.3 ± 4.7 and 34.1 ± 5.7 mg / mg, respectively, P < 0.05), HASM tension ((12.1 ± 2.7), (30.9 ± 7.0), (41.2 ± 9.23 and 53.1 ± 12.3 mg / mg) were significantly higher than those in the control group (8.6 ± 1.9, 22.8 ± 4.8, 30.9 ± 5.4 and 38.3 ± 7.9 mg / mg, respectively) ). HASM tension of histamine and PMA increased with increasing concentration in a dose-dependent manner. The contraction of HSAM induced by PMA in both groups was completely inhibited by Ro31-8220 and nifedipine. Conclusions Activation of PKC leads to an increase in the tension of HASM, which is more pronounced in HASM that is passively sensitized in vitro.