麻杏石甘汤对RSV诱导哮喘小鼠肺组织炎症反应的影响及机制

Effects of Maxing Shigan decoction on lung inflammatory response of asthmatic mice inducted by RSV

目的探讨麻杏石甘汤(MGD)对呼吸道合胞病毒(RSV)诱导哮喘小鼠肺组织炎症反应的影响及机制。方法将50只SPF级雄性Balb/c小鼠随机分为正常组、模型组、MGD高剂量(MGDH)组、MGD低剂量(MGDL)组、阳性药对照组,每组10只。除正常组外,其余各组通过致敏、诱喘、RSV激发哮喘建立模型。末次RSV激发2 h后,MGDH组、MGDL组分别给予12、6 mg/(kg·d)MGD灌胃,阳性药对照组给予顺尔宁0.6 mg/(kg·d)灌胃,正常组、模型组给予等量生理盐水灌胃,均每天1次,连续灌胃7 d。于末次给药2 h后,用水合氯醛麻醉小鼠,经腹主动脉取血,分离血清,取小鼠肺组织。经HE染色于显微镜下观察肺组织病理变化,用ELISA法检测小鼠血清中IL-10、IL-17,用免疫组化法检测肺组织中Janus激酶1(JAK1)、信号转导及转录激活因子6(STAT6)蛋白表达。结果与正常组比较,模型组血清IL-10水平低、IL-17水平高(P均<0.05);与模型组比较,MGDH组、MGDL组血清IL-10水平高、IL-17水平低(P均<0.05);与MGDL组比较,MGDH组、阳性药对照组血清IL-10水平高、IL-17水平低(P均<0.05);MGDH组、阳性药对照组血清IL-10、IL-17水平比较差异无统计学意义(P均>0.05)。与正常组比较,模型组肺组织中JAK1、STAT6蛋白相对表达量高(P均<0.05);与模型组比较,MGDL组、MGDH组、阳性药对照组肺组织中JAK1、STAT6蛋白相对表达量低(P均<0.05);与MGDL组比较,MGDH组肺组织中STAT6蛋白相对表达量低(P<0.05),阳性药对照组肺组织中JAK1、STAT6蛋白相对表达量低(P均<0.05);MGDH组、阳性药对照组肺组织中JAK1、STAT6蛋白相对表达量比较差异无统计学意义(P均>0.05)。结论麻杏石甘汤可有效改善RSV诱导哮喘小鼠肺组织的炎症状态,其机制可能与改善Treg/Th17失衡及JAK/STAT信号通路有关。

Objective To observe the influence of Maxing Shigan decoction(MGD)on the inflammatory response in lung tissues of asthmatic rats induce by respiratory syncytial virus(RSV).Methods Fifty male Balb/c rats were randomly divided into the normal group,model group,MGDH group,MGDL group,and positive control group,with 10 rats in each group.Except the control group,rats in the other groups were treated by repeated inhalation of OVA combined with repeated intranasal instillation of RSV.After successfully establishing the asthma models,the rats in the MGDH group and the MGDL group were administered 12 g/(kg·d)and 6 g/(kg·d)MGD and rats in the positive group were given Singulair 0.6 mg/(kg·d),rats in the normal group and the model group were given an equal amount of normal saline.We isolated the serum and lung tissues in mice after 7 days.The histopathological changes in lung tissues were detected by HE staining.Immunohistochemistry staining was used the detect the expression levels of JAK1 and STAT6 protein.ELISA was used the detect the expression levels of IL-10 and IL-17.Results Compared with the normal group,the level of IL-10 decreased and IL-17 increased in the model group(both P<0.05).Compared with the model group,the level of IL-10 was higher and the level of IL-17 was lower in the MGDH and MGDL groups(both P<0.05).Compared with MGDL group,the level of IL-10 was higher and IL-17 was lower in the MGDH group and positive control group(both P<0.05).There was no significant difference in the levels of IL-10 and IL-17 between MGDH group and positive control group(both P>0.05).Compared with the normal group,the protein levels of JAK1 and STAT6 in the lung tissue increased in the model group(both P<0.05).Compared with the model group,the protein levels of JAK1 and STAT6 in the lung tissues decreased in the other groups(both P<0.05).Compared with the MGDL group,the protein expression of STAT6 in the lung tissue of MGDH group was lower,and both the protein expression levels of JAK1 and STAT6 decreased in the positive control group(both P<0.05).In addition,there was no significant difference in the levels of JAK1 and STAT6 between the MGDH group and positive control group(both P>0.05).Conclusion MGD can effectively improve RSV-induced lung inflammation in asthmatic mice,and its mechanism may be related to the improvement of Treg/Th17 imbalance and JAK/STAT signaling pathway.