异鼠李素抑制卵清蛋白诱导的哮喘小鼠肺部炎症

Isorhamnetin inhibits ovalbumin-induced pulmonary inflammation in asthmatic mice

目的:探讨异鼠李素对哮喘模型小鼠肺炎的影响并初步分析其机制。方法:将32只BALB/c小鼠随机分为正常对照组、哮喘模型组、异鼠李素低剂量(50 mg/kg)治疗组和异鼠李素高剂量(150 mg/kg)治疗组。利用卵清蛋白(ovalbumin,OVA)构建小鼠哮喘模型。HE染色和PAS染色观察肺组织病理学变化;ELISA检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中半胱氨酰白三浠1(cysteinyl leukotriene 1,CysLT1)、半胱氨酰白三烯受体1(cysteinyl leukotriene receptor 1,CysLTR1)、白细胞介素4(interleukin-4,IL-4)、IL-5、IL-13和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)的含量;免疫组织化学染色检测肺组织中活化T细胞核因子4(nuclear factor of activated T cells 4,NFATc4)的表达;Western blot实验检测肺组织中NFATc4、细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)和血管细胞黏附分子1(vascular cell adhesion molecule-1,VCAM-1)蛋白的表达。结果:异鼠李素可改善OVA诱导的哮喘模型小鼠肺组织病理学改变,降低BALF中CysLT1、CysLTR1、IL-4、IL-5、IL-13和TNF-α的含量,降低肺组织中NFATc4、ICAM-1和VCAM-1的表达。结论:异鼠李素可抑制哮喘模型小鼠肺组织炎症反应,其机制可能与抑制calcineurin/NFATc4通路的活化有关。

AIM:To investigate the effect of isorhamnetin on pulmonary inflammation in asthmatic mice and to analyze its primary mechanism.METHODS:BALB/c mice were randomly divided into normal control group,asthma model group,isorhamnetin low-dose(50 mg/kg)treatment group and isorhamnetin high-dose(150 mg/kg)treatment group.Ovalbumin(OVA)was used to establish a mouse asthma model.HE staining and PAS staining were used to observe the pathological changes of lung tissue.The contents of cysteinyl leukotriene1(CysLT1),cystelinyl leukotriene receptor 1(CysLTR1),interleukin-4(IL-4),IL-5,IL-13 and tumor necrosis factor-α(TNF-α)in bronchoalveolar lavage fluid(BALF)were measured by ELISA.The expression of nuclear factor of activated T cells 4(NFATc4)in lung tissue was detected by immunohistochemical staining.The protein expression of NFATc4,intercellular cell adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)was determined by Western blot.RESULTS:Isorhamnetin improved histopathological changes in OVA-induced asthma model mice,reduced the contents of CysLT1,CysLTR1,IL-4,IL-5,IL-13 and TNF-αin BALF,and reduced NFATc4,ICAM-1 and VCAM-1 expression in lung tissue(P<0.05).CONCLUSION:Isorhamnetin inhibits the inflammatory response of lung tissue in asthmatic model mice,and the mechanism may be related to the inhibition of the calcineurin/NFATc4 signaling pathway.