班布特罗对哮喘豚鼠T淋巴细胞凋亡的影响及作用机制

EFFECTS OF BAMBUTEROL ON APOPTOSIS OF T LYMPHOCYTES IN ASTHMATIC GUINEA PIGS AND ITS MECHANISM

目的 观察 β2 受体激动剂班布特罗 (bambuterol)对哮喘豚鼠T淋巴细胞凋亡的影响并探讨其作用机制。方法 卵白蛋白 (OA)建立豚鼠哮喘模型 ,支气管肺泡灌洗液 (BALF)分离T淋巴细胞 ,采用原位末端标记法 (TUNEL)检测细胞凋亡 ,免疫组化染色方法观察T淋巴细胞核因子 κB(NF κB)蛋白表达。结果 班布特罗大剂量组和中剂量组可明显降低哮喘豚鼠BALF中淋巴细胞数及T淋巴细胞NF κB表达 ,增加T淋巴细胞凋亡 ,而β 受体阻断剂普奈洛尔可拮抗这一作用。Pear son相关分析显示 ,T淋巴细胞NF κB表达与细胞凋亡之间呈明显的负相关关系。结论 大、中剂量班布特罗可能通过cAMP PKA途径来抑制NF κB活化 ,从而进一步促进T淋巴细胞的凋亡。

Objective: To investigate the effects of β_2-adrenergic agonist bambuterol on apoptosis of T lymphocytes in asthmatic guinea pigs and its mechanism. Methods: Guinea pigs were sensisized by ovalbumin and T lymphocytes in BALF were isolated. The apoptosis of T lymphocytes was detected by TdT-mediated dUTP nick end labeling(TUNEL) and the expression of NF-κB on T lymphocytes was observed by immunohistochemical staining. Results: High dose and medium dose of bambuterol decreased the number of lymphocytes and expression of NF-κB on T lymphocytes and increased apoptosis of T lymphocytes in bronchoalveolar lavage fluid(BALF) of asthmatic guinea pigs significantly,while these effects were completely abolished by pretreatment with propranolol. Furthermore,there was a significantly negative correlation between the expression of NF-κB and the apoptosis of T lymphocytes( P <0.05). Conclusion: Inhibiting the activation of NF-κB by cAMP-PKA pathway may be one of the mechamisms for bambuterol to promote apoptosis of T lymphocytes.