瞬时电位感受器香草酸受体1在哮喘小鼠气道炎症中的作用研究

Role of transient receptor potential vanilloid 1 in airway inflammation in asthmatic mice

摘要:

目的 观察瞬时电位感受器香草酸受体1 （TRPV1）通道活性改变对哮喘模型小鼠气道炎症程度的影响。方法 将BALB/c小鼠随机分为对照组、哮喘组、辣椒素 （TRPV1激动剂）组、辣椒平 （TRPV1拮抗剂）组、地塞米松组。采用卵清蛋白-氢氧化铝混合液腹腔注射致敏并雾化激发构建哮喘小鼠模型。辣椒素、辣椒平和地塞米松组分别在每次激发前30 min腹腔注射辣椒素 （30 μg/kg）、辣椒平 （10 μmol/kg）及地塞米松 （2 mg/kg）。采用苏木精-伊红染色观察各组小鼠肺部炎症程度；ELISA法检测肺泡灌洗液 （BALF）中IL-8和IL-13的含量；Real-Time PCR法检测小鼠肺组织中TRPV1 mRNA的相对含量。结果 与哮喘组比较，辣椒平组和地塞米松组肺部炎症程度减轻，辣椒素组炎症程度明显加重。与对照组比较，哮喘组、辣椒素组小鼠BALF中IL-13、IL-8含量及肺组织TRPV1 mRNA表达明显增加 （P < 0.05）；与哮喘组比较，辣椒平组、地塞米松组BALF中IL-13、IL-8含量及肺组织TRPV1 mRNA表达明显降低 （P < 0.05），辣椒素组BALF中IL-13、IL-8含量明显增加 （P < 0.05）。结论 TRPV1通道激活剂和通道抑制剂可影响哮喘小鼠肺部炎症程度。地塞米松可能通过调节TRPV1水平减轻气道炎症。

Abstract:

Objective To study the effects of the change in transient receptor potential vanilloid 1 (TRPV1) channel activity on the degree of airway inflammation in asthmatic mice. Methods BALB/c mice were randomly divided into control, asthma, capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist), and dexamethasone groups. The asthmatic mouse model was established by intraperitoneal injection of mixed ovalbumin-aluminium hydroxide solution and ultrasonic atomization with OVA for sensitization and challenge. The capsaicin, capsazepine, and dexamethasone groups were given intraperitoneal injection of capsaicin (30 μg/kg), capsazepine (10 μmol/kg), and dexamethasone (2 mg/kg) respectively, at 30 minutes before challenge. Hematoxylin and eosin staining was used to observe the degree of pulmonary inflammation. ELISA was used to measure the content of interleukin-8 (IL-8) and interleukin-13 (IL-13) in bronchoalveolar lavage fluid (BALF). Real-Time PCR was used to measure the relative content of TRPV1 mRNA in lung tissue. Results Compared with the asthma group, the capsazepine and dexamethasone groups showed reduced pulmonary inflammation, while the capsaicin group showed aggravated pulmonary inflammation. Compared with the control group, the asthma and capsaicin groups showed increases in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P < 0.05). Compared with the asthma group, the capsazepine and dexamethasone groups showed reductions in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P < 0.05). The capsaicin group showed increases in the content of IL-13 and IL-8 in BALF (P < 0.05). Conclusions TRPV1 channel agonist and antagonist can influence the degree of airway inflammation in asthmatic mice. Dexamethasone may reduce airway inflammation through regulating TRPV1 level.