三氧化二砷对小鼠过敏性哮喘的治疗作用及机制

Therapeusis of arsenic trioxide on asthma in mice and its possible mechanisms

目的 :研究三氧化二砷对小鼠过敏性哮喘的治疗作用及对脾T细胞周期和Bcl 2基因表达的影响。方法 :用卵蛋白建立小鼠过敏性哮喘模型 ,收集肺泡灌洗液 (BALF) ,直接计算白细胞总数和分类 ,双缩脲法检测总蛋白含量 ,应用Medlab生物信号采集系统软件检测小鼠肺功能 ,流式细胞术和免疫荧光法检测脾及BALF中T细胞数、T细胞周期和Bcl 2基因表达的变化。结果 :三氧化二砷可使BALF中总蛋白含量下降 ,白细胞总数减少 ,嗜酸细胞和淋巴细胞减少 ,改善哮喘小鼠肺功能 ;使脾及BALF中T细胞数降低 ;在 1.15mg·kg-1的剂量时可诱导脾T细胞凋亡 ,在 4 .6 0mg·kg-1的剂量时抑制其活化增殖 ;可下调脾T细胞Bcl 2基因表达。结论 :三氧化二砷有平喘作用 ,其作用机制可能与其调节T细胞的激活与凋亡 ,下调Bcl 2基因表达有关。

AIM : To study the therapeusis of arsenic trioxide on asthma and the effects of arsenic on T cell cycle and Bcl-2 expression in asthmatic mice. METHODS : 49 healthy Kunming male mice at 5 wk of age were randomly divided into 7 groups: control group, asthmatic group, dexamethasone group and arsenic group (the mice were given arsenic trioxide 0.575, 1.15, 2.3, and 4.6 mg·kg -1 before challenge). An animal model of asthma was established by means of OVA sensitizing-challenging. Pulmonary functions in those mice were measured by Organism Signal Collection System software. Total leucocytes and its cell classification, protein concentrations, and pulmonary function were detected. CD 3 expression, T cell cycle and Bcl-2 expression were detected by flow cytometry. RESULTS : In those groups treated with arsenic trioxide, compared with asthmatic group, the pulmonary function improved, the count of total leucocytes, eosinophils, lymphocytes and protein concentrations decreased. There were double effects of arsenic trioxide on T cell in spleen: induction apotosis in the dose of 1.15 mg·kg -1, inhibition proliferation and activation in the dose of 4.6 mg·kg -1. The Bcl-2 expression in every group treated with arsenic trioxide was lower than that of asthmatic group, and the effect was in a dose-dependent manner. CONCLUSION : There are therapeutic effects of arsenic trioxide on asthma. The mechanisms may be ascribed to the effects of arsenic trioxide on apotosis and activation and the Bcl-2 expression of T cells.