哮喘豚鼠肺组织嗜酸性粒细胞Fas表达及药物的影响

Fas expression on eosinophils in lungs and its changes after treatment in asthmatic guinea pigs

目的：研究哮喘时嗜酸性粒细胞（Ｅｏｓ）凋亡与Ｆａｓ表达的关系及药物对它们的影响。方法：应用地塞米松（ＤＭ）、雷公藤甲素（Ｔｒｉｐｔｏｌｉｄｅ，ＴＰ）及氨茶碱（ＡＭ）干预哮喘豚鼠，以ＴＵＮＥＬ法检测细胞凋亡，以ＲＴ－ＰＣＲ及原位杂交检测ＦａｓｍＲＮＡ表达。结果：哮喘组Ｅｏｓ凋亡率较正常对照组显著降低（Ｐ＜０．０１），应用ＤＭ、ＴＰ、ＡＭ后均显著增加（Ｐ＜０．０１）。正常豚鼠Ｅｏｓ可检测到ＦａｓｍＲＮＡ表达，不同密度Ｅｏｓ表达差异不显著（Ｐ＞０．０５）。哮喘组ＦａｓｍＲＮＡ明显减少，以低密度Ｅｏｓ减少明显（Ｐ＜０．０５），应用ＤＭ、ＴＰ、ＡＭ后其表达明显增加。结论：凋亡调节的缺失是导致组织及血中Ｅｏｓ增多的重要原因，Ｆａｓ抗原参与了哮喘Ｅｏｓ凋亡的调节，低密度Ｅｏｓ更能反映哮喘的特征。ＤＭ、ＴＰ、ＡＭ可促进哮喘肺组织中的Ｅｏｓ表达Ｆａｓ抗原，进而加强细胞凋亡。

Objective: To determine the relationship between the apoptosis of asthmatic eosinophils and Fas expression and its changes after treated with drugs. Methods: After the asthmatic guinea pigs were treated with dexamethasone (DM), triptolide (TP) and aminophylline (AM), apoptosis of the eosinophils was detected by TdTmediated dUTP nick end labeling and Fas mRNA expression measured by RTPCR and in situ hybridization. Results: The number of the apoptotic eosinophils was significantly lower in asthmatic group than in the control (P<0.01) and markedly increased after treated with DM,TP and AM (P<0.01).Fas mRNA of the eosinophils was moderately expressed in normal guinea pigs,decreased in asthmatic ones and significantly increased after treatment with the 3 agents (P<0.05). Conclusion: Fas may be one of the important factors regulating apoptosis of eosinophils in asthma.DM,TP and AM can upregulate the Fas expression to promote apoptosis of eosinophils in the lungs of guinea pigs after asthma.