外源性H2S干预对O3致哮喘小鼠气道反应性和气道重塑的影响

 目的: 探讨外源性硫化氢(hydrogen sulfide,H₂S)对臭氧(ozone,O₃)致哮喘小鼠气道反应性和气道重塑的影响。方法: 将15只SPF级C57BL/6雌性小鼠随机分为对照组、O₃组和NaHS+O₃组,每组5只。O₃处理前0.5 h,对照组和O₃组腹腔注射生理盐水,NaHS+O₃组腹腔注射NaHS(H₂S的供体);O₃组和NaHS+O₃组隔天用O₃处理,对照组则呼吸清洁空气。持续4周后无创测定小鼠的气道反应性,随后进行气管环张力测定,通过肺组织HE染色测定支气管基底膜周径(Pbm)和管壁总面积(Wat)并标准化衡量气道重塑程度,并行AB-PAS染色测定肺组织中杯状上皮细胞的变化情况以进一步评价气道重塑程度。结果: 与对照组相比,O₃组小鼠的气道反应性显著增高;NaHS+O₃组明显低于O₃组,但与对照组相比差异无统计学显著性。与对照组相比,O₃组小鼠在乙酰甲胆碱刺激时的气管收缩力显著加大;NaHS+O₃组明显小于O₃组。与对照组相比,O₃组小鼠的支气管壁厚度明显加大;NaHS+O₃组显著小于O₃组但仍大于对照组。与对照组相比,O₃组小鼠肺组织中杯状上皮细胞占气道上皮细胞总面积的百分比显著上升;NaHS+O₃组显著低于O₃组但仍高于对照组。结论: 外源性H₂S对O₃所致哮喘的气道高反应性和气道重塑有缓解与保护作用,有望为临床药物治疗哮喘提供新靶点。

Effects of exogenous H2S on O3-induced airway hyperresponsiveness and airway remodeling in a mouse model of asthma

AIM: To investigate the effects of exogenous hydrogen sulfide (H₂S) on ozone (O₃)-induced airway hyperresponsiveness and airway remodeling in a mouse model of asthma. METHODS: Female SPF C57BL/6 mice were randomized as control group, O₃ group and NaHS+O₃ group. Half an hour before O₃ treatment, the mice in control group and O₃ group were intraperitoneally injected with normal saline, while the mice in NaHS+O₃ group were intraperitoneally injected with NaHS (H₂S donor); then the mice in O₃ and NaHS+O₃ group were treated with O₃, while the mice in control group breathed clean air. After 4 weeks, the airway responsiveness and tracheal ring tension were measured. The bronchial basement membrane circle diameter (Pbm) and the total area of the wall (Wat) were determined with HE staining and standardized to measure airway remodeling. The changes of goblet epithelial cells in the lung tissue were determined with AB-PAS staining. RESULTS: Airway tension of O₃ group was significantly higher than that in control group, but that in NaHS+O₃ group was obviously lower than that in O₃ group and had no significant difference compared with control group. Compared with control group, the tension of tracheal ring stimulated by methacholine in O₃ group increased significantly, but that in NaHS+O₃ group decreased obviously compared with O₃ group and had no significant change compared with control group. Compared with control group, bronchial wall thickness in O₃ group increased significantly, but that in NaHS+O₃ group decreased obviously compared with O₃ group and increased significantly compared with control group. Compared with control group, goblet epithelial cell proportion in the total area of airway epithelial cells in O₃ group increased significantly, but that in NaHS+O₃ group decreased compared with O₃ group and increased significantly compared with control group. CONCLUSION: Exogenous H₂S reduces O₃-induced airway hyperresponsiveness and airway remodeling, thus providing a new target for clinical drug treatment of asthma.