血红素类物质与哮喘发作关系的初步探讨

Relationship between Heme Substances and Asthmatic Attack

目的 探讨血红素类物质在哮喘中的变化及与哮喘发作的关系。方法 6 0只豚鼠随机分为正常对照组、哮喘、哮喘自然缓解、地塞米松、血红素氧合酶 1(HO-1)特异性激动剂血晶素和抑制剂锡原卟啉 6组。每组均检测肺组织病理和HO-1的蛋白表达 (免疫组化染色法 ) ,应用分光光度法检测肺组织HO-1活性、血一氧化碳血红蛋白 (COHb)和NO含量 ,放射免疫竞争抑制法测定肺环磷酸鸟苷 (cGMP)。结果 哮喘组和血晶素组①肺HO-1活性 ;②血COHb ;③NO ;④肺cGMP含量与正常组比较 ,差异非常显著 (t值分别为① 5 .6 9,9.2 9,② 6 .2 8,10 .19,③ 5 .77,8.92 ,④ 9.74,6 .96 ,P <0 .0 1) ,血晶素组更为显著。肺HO-1活性 :每小时 (144 9± 42 6 ) pmol/mg ;血COHb (7.43± 2 .0 7) % ;血NO(90 .9± 16 .7) μmol/L ;肺cGMP :(1.96± 0 .6 5 ) pmol/mg ;肺有明显的嗜酸细胞浸润 ,HO-1蛋白表达≥ 4级。锡原卟啉抑制、地塞米松防治和哮喘自然缓解组各项检测指标显著下降 ,与哮喘组比较差异显著 (P <0 .0 1)。结论 哮喘时 ,体内血红素代谢产物CO和NO、降解血红素的HO-1酶类及其血红素酶类增加 ;血红素类物质增加 ,可能参与哮喘气道高反应性。

Objective To explore the change of heme substances in asthma and the relationship between heme substances and asthmatic attack. Methods Sixty guinea pigs were equally separated into 6 groups. Except for normal control group (NCG), asthmatic models were divided into 5 groups. Two of them were treated with the specific stimulator (hemin) and the inhibitor (Sn-PP)of HO -1 respectively, the other group received dexamethasone as a preventive measure, and the last were asthmatic and nature rescuing asthmatic groups (NRAG). In all the tested animals, the COHb and NO in blood, lung HO -1 activity, and lung cGMP were examined. The lung tissues were pathologically observed and stained immunohistochemically. Results In the asthmatic (AG) and heme stimulated groups (HG), the levels of the COHb, NO, lung HO -1 activity and cGMP were significantly increased compared with NCG (t values were ① 5.69 in AG, 9.29 in HG, ② 6.28 , 10.19 , ③ 5.77 , 8.92 , ④ 9.74 , 6.96 ,P< 0.01 , respectively). Lung HO -1 activities were (1449±426) pmol/mg. COHb in blood ( 7.43 ± 2.07 )%, NO in blood ( 90.9 ± 16.7 ) μmol/L, lung cGMP ( 1.96 ± 0.65 ) pmol/mg, and lung HO -1 protein expression ≥4 grade in hemin stimulated group respectively. Whereas, in the Sn-pp inhibited, dexamethasone and NSAG groups, they were markedly reduced compared with the asthmatic group (P< 0.01 ). Conclusions In asthma, the increased NO, cGMP induced by NOS and sGC, and HO -1 protein suggest that heme substances catalyzed by HO are enhanced. These may be contributory to airway hyperresponsiveness.