胃饥饿素治疗小鼠支气管哮喘的作用机制及对细胞焦亡的影响

The mechanism of ghrelin in treating mice with bronchial asthma and its effect on pyroptosis

目的探讨胃饥饿素对小鼠支气管哮喘的治疗作用及对细胞焦亡的影响。方法将30只小鼠随机分为对照组、模型组[卵清蛋白(OVA)造模]和治疗组(OVA联合胃饥饿素),每组10只。构建小鼠哮喘模型,应用病理学和乙酰甲胆碱的反应性评估气道损伤情况。采用酶联免疫吸附法(ELISA)测定肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素-5(IL-5)和白细胞介素-13(IL-13)水平。应用免疫组化及病理学评估胃饥饿素对小鼠哮喘的治疗作用。通过Western blot分析肺组织中细胞焦亡相关蛋白的表达水平。结果形态学结果显示,治疗组巨噬细胞浸润和炎性评分显著改善(P<0.05)。Masson染色及气道反应性检测发现治疗组小鼠肺纤维化显著改善,呼吸系统阻力显著降低(P<0.05)。与模型组相比,治疗组白细胞总数显著降低(P<0.05)。治疗组治疗后TNF-α、IFN-γ、IL-5及IL-13表达水平显著低于模型组(P<0.05)。肺组织中NLRP3表达量显著降低,NLRP3、Caspase-1及白细胞介素-1B(IL-1B)表达水平显著降低(P<0.05)。结论胃饥饿素可通过减轻细胞焦亡程度治疗哮喘,其可能为治疗哮喘提供新的思路。

Objective To investigate the therapeutic effect of ghrelin in mice with bronchial asthma and its effect on pyroptosis.Methods Thirty mice were randomly divided into control group,model group[ovalbumin(OVA)modeling]and treatment group(OVA combined with ghrelin),with 10 cases in each group.Mouse model of asthma was established,and airway injury was assessed by pathology and acetylcholine reactivity.The levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-5(IL-5)and interleukin-13(IL-13)in bronchoalveolar lavage fluid(BALF)were determined by enzyme-linked immunosorbent assay(ELISA).Immunohistochemistry and pathology were used to evaluate the therapeutic effect of ghrelin on asthma in mice.The expression levels of pyroptosis related proteins in lung tissues were analyzed by Western blot.Results Morphological results showed that the macrophage infiltration and inflammatory scores were significantly improved in the treatment group(P<0.05).Masson staining and airway reactivity test showed that pulmonary fibrosis was significantly improved and respiratory resistance was significantly decreased in the treatment group(P<0.05).Compared with model group,the total white blood cell count in treatment group was significantly decreased(P<0.05).After treatment,the expression levels of TNF-α,IFN-γ,IL-5 and IL-13 in treatment group were significantly lower than those in model group(P<0.05).NLRP3 expression in lung tissue was significantly decreased,and the expression levels of NLRP3,caspase-1 and interleukin-1B(IL-1B)were significantly decreased in the treatment group(P<0.05).Conclusion Ghrelin can treat asthma by reducing the degree of pyroptosis,which may provide a new idea for the treatment of asthma.