miR155STAT6在大气PM2.5加重大鼠哮喘中的作用

Roles of miR155 and STAT6 in exacerbation of asthma in rats induced by atmospheric PM2.5

  • 摘要:
    目的 观察不同浓度大气PM2.5对哮喘大鼠的影响,并初步探索PM2.5诱导大鼠哮喘加重过程中miR155STAT6IL-13的变化。

    方法 将50只SD大鼠随机分为:对照组,哮喘组,哮喘+PM2.5低染毒组、哮喘+PM2.5中染毒组及哮喘+PM2.5高染毒组。对照组和哮喘组均给予生理盐水1.5 mL/kg(以每千克体重计,下同),哮喘+低、中、高染毒组分别给予PM2.5生理盐水混悬液1.5、6.0、24.0 mg/kg。通过腹腔注射卵清蛋白(OVA)致敏,雾化吸入OVA构建大鼠哮喘模型,第25、28、31、34天予以PM2.5气管滴注染毒。第36天处死大鼠后,观察肺脏HE染色病理切片,比较各组大鼠支气管肺灌洗液(BALF)中细胞总数及分类计数;通过RT-PCR检测大鼠肺组织中miR155STAT6(信号转导和转录激活因子6)、IL-13的基因表达水平;ELISA检测大鼠BALF中IL-13蛋白水平。

    结果 哮喘组大鼠BALF中嗜酸粒细胞百分比高于对照组,哮喘+PM2.5中、高染毒组高于对照组及哮喘组,差异均有统计学意义(P < 0.05);哮喘+PM2.5中、高染毒组大鼠肺组织miR155STAT6基因表达水平高于对照组,差异均有统计学意义(P < 0.05);大鼠肺组织miR155STAT6基因表达呈明显正相关(r=0.843,P < 0.001);5组大鼠肺组织IL-13基因及BALF中IL-13蛋白表达水平间的差异无统计学意义(P > 0.05)。

    结论 miR155STAT6可能在PM2.5加重哮喘过程中起作用,并且miR155STAT6之间存在关联。

     

    Abstract:
    Objective To observe the effects of different concentrations of atmospheric PM2.5 on asthmatic rats, and the changes of miR155, STAT6, and IL-13 associated with asthma exacerbation.

    Methods A total of 50 SD rats were randomly assigned into five groups, including normal saline control group, asthma group, asthma+PM2.5 low dose group, asthma+PM2.5 medium dose group, and asthma+ PM2.5 high dose group. The control group and asthma group were treated with normal saline (1.5 mg/kg body weight), and the asthma+ PM2.5 exposure groups were treated with mixture of PM2.5 and normal saline (1.5, 6.0, and 24.0 mg/kg). An asthma rat model was reproduced by sensitization with intraperitoneal in jection and inhalation of ovalbumin (OVA). On day 25, 28, 31 and 34, the rats were administrated with PM2.5 by intratracheal in stillation, and sacrificed on day 36. We observed pathological changes of rat lung tissue samples by HE staining. Total and differential cell counts in bronchoalveolar lavage fluid (BALF) were compared across groups. Expression levels of miR155, STAT6, and IL-13 in rat lung tissue samples were analyzed by RT-PCR. Level of IL-13 in BALF was detected by ELISA.

    Results The percentage of eosinophilic in the asthma group was higher than that in the control group, and the percentages in the asthma+PM2.5 medium and high dose group were higher than the control, asthma group, the differences were statistically significant (P < 0.05). The expression of miR155 and STAT6 in the asthma+PM2.5 medium and high dose groups were higher than that in the control group (P < 0.05). There was a positive correlation between the expressions of miR155 and STAT6 genes (r=0.843, P < 0.001). The gene expressions of IL-13 in rat lung tissue and the protein expression level of IL-13 in BALF were not different (P > 0.05).

    Conclusion miR155 and STAT6 may play a role in the exacerbation of asthma induced by atmospheric PM2.5, and miR155 and STAT6 may be related.

     

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