哮喘豚鼠血红素氧合酶1的表达与调节

The expression and regulation of heme oxygenase 1 in asthmatic guinea pigs

目的 探讨血红素氧合酶１（ＨＯ１） 在哮喘中的表达与作用机制。方法 ７０ 只豚鼠完全随机分为７ 组，每组１０ 只，其中两组分别应用ＨＯ１ 特异性激动剂血晶素和抑制剂锡原卟啉处理豚鼠哮喘模型，另外５ 组分别为哮喘发作前、发作、自然缓解、地塞米松预防和正常对照组，应用分光光度计和放射免疫竞争分析法等，检测血及肺组织的ＨＯ１ 活性、一氧血红蛋白（ＣＯＨｂ）、环磷酸鸟苷（ｃＧＭＰ） 、血浆ＩｇＥ 水平，观察支气管肺泡灌洗液（ＢＡＬＦ） 中细胞数、肺组织病理学和ＨＯ１ 免疫组织化学染色的变化。结果 哮喘发作组和血晶素激动组的各项指标与正常对照组比较，差异均有非常显著性（ｔ＝４－７５４～１０－１８８，Ｐ＜０－０１） ，血晶素组更为显著，如肺ＨＯ１ 活性：每小时每毫克蛋白生成胆红素量为（１４４９±４２６）ｐｍｏｌ；肺ＣＯＨｂ：每毫克蛋白含（０－８３ ±０－２９） ％ ；肺ｃＧＭＰ：每毫克蛋白含（１－９６ ±０－６５）ｐｍｏｌ；血浆ＩｇＥ：（７３±２１） ｋＵ／Ｌ；ＨＯ１ 蛋白表达≥４ 级；ＢＡＬＦ细胞总数：（２１±４） ×１０８／Ｌ。地塞米松预防组和锡原卟啉抑制组除ＣＯ 含量和肺ＨＯ１ 活性略高外。

Objective To explore the expression and pathogenic mechanism of heme oxygenase 1(HO 1 ) in asthma Methods Two groups of guinea pigs (10 in each) were treated with the specific stimulator(hemin) and inhibitor(Sn PP) of HO 1 respectively Their effects on the levels of HO 1 activity, COHb, cGMP and IgE in serum or blood and lung tissues were compared with each other Acute asthmatic group (AAG), dexamethasone prevented group(DPG), stable asthmatic group, ovalbumin sensitized group and normal control group(NCG) were also included Lung tissues of tested animals were pathologically observed and immunohistochemically stained Results In the AAG and hemin stimulated group, the levels of COHb, cGMP and IgE were significantly increased with higher levels of activity and expression of HO 1 protein compared with the NCG ( t =4 575～10 188, P <0 01) In DPG and Sn PP inhibited groups, however, all measured parameters were markedly reduced compared with the AAG( P <0 01) The other groups were normal Conclusions The increased production and activity of HO 1 resulted in increases of endogenous CO and cGMP and promoted inflammation and immunoreaction in asthma