外源性H_2S干预对O_3致哮喘小鼠气道反应性和气道重塑的影响

Effects of exogenous H_2S on O_3-induced airway hyperresponsiveness and airway remodeling in a mouse model of asthma

目的:探讨外源性硫化氢(hydrogen sulfide,H_2S)对臭氧(ozone,O_3)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、O_3组和NaHS+O_3组,每组5只。O_3处理前0.5 h,对照组和O_3组腹腔注射生理盐水,NaHS+O_3组腹腔注射NaHS(H_2S的供体);O_3组和NaHS+O_3组隔天用O_3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,O_3组小鼠的气道反应性显著增高;NaHS+O_3组明显低于O_3组,但与对照组相比差异无统计学显著性。与对照组相比,O_3组小鼠在乙酰甲胆碱刺激时的气管收缩力显著加大;NaHS+O_3组明显小于O_3组。与对照组相比,O_3组小鼠的支气管壁厚度明显加大;NaHS+O_3组显著小于O_3组但仍大于对照组。与对照组相比,O_3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+O_3组显著低于O_3组但仍高于对照组。结论:外源性H_2S对O_3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。

AIM： To investigate the effects of exogenous hydrogen sulfide （H2 S） on ozone （03 ）-induced air- way hyperresponsiveness and airway remodeling in a mouse model of asthma. METHODS： Female SPF C57BL/6 mice were randomized as control group, O3 group and NariS ＋ 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 NariS ＋ O3 group were intraperito- neally injected with NariS （H2S donor） ; then the mice in O3 and NariS ＋ 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 stai- ning and standardized to measure airway remodeling. The changes of goblet epithelial ceils in the lung tissue were deter- mined with AB-PAS staining. RESULTS ： Airway tension of O3 group was significantly higher than that in control group, but that in NariS ＋ O3 group was obviously lower than that in O3 group and had no significant difference compared with con- trol group. Compared with control group, the tension of tracheal ring stimulated by methacholine in O3 group increased sig- nificantly, but that in NariS ＋ O3 group decreased obviously compared with O3 group and had no significant change com-pared with control group. Compared with control group, bronchial wall thickness in O3 group increased significantly, but that in Naris ＋ 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 deereased compared with O3 group and increased significantly com- pared with control group. CONCLUSION： Exogenous H2S reduces O3-indnced airway hyperresponsiveness and airway re- modeling, thus providing a new target for clinical drug treatment of asthma.