热感赛比斯坦颗粒调控MAPK/NF-κB通路改善哮喘小鼠气道炎症反应OA
Regan Saibisitan Granules alleviate airway inflammatory responses in asthmatic mice by regulating MAPK/NF-κB pathway
探究热感赛比斯坦颗粒(RGS)通过调控丝裂原活化蛋白激酶(MAPK)/核因子 κB(NF-κB)信号通路改善哮喘小鼠气道炎症反应的作用及机制.将雌性 Balb/c 小鼠按体质量随机分为空白组,模型组,RGS 低、中、高(0.75、1.5、3 g·kg-1)剂量组,地塞米松(3 mg·kg-1)组,肺宁片(0.72 g·kg-1)组.采用卵清蛋白(OVA)致敏和雾化激发的方法诱导哮喘模型.对支气管肺泡灌洗液(BALF)中白细胞(WBC)、嗜酸性粒细胞(EOS)、中性粒细胞(NEU)、淋巴细胞(LYM)数目计数;采用酶联免疫吸附测定(ELISA)试剂盒检测 BALF 中白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、白细胞介素-13(IL-13)、干扰素-γ(INF-γ)及血清中免疫球蛋白 E(IgE)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)分泌情况;采用苏木精-伊红、过碘酸希夫染色观察肺组织病理改变,以综合评估 RGS 对哮喘小鼠的炎症改善作用.蛋白免疫印迹法检测肺组织中磷酸化细胞外信号调节激酶 1/2(p-ERK1/2)、磷酸化 c-Jun 氨基末端激酶(p-JNK)、磷酸化 MAPK(p-p38)、磷酸化 NF-κB(p-NF-κB)、磷酸化核因子κB 抑制蛋白 α(p-IκBα)、活化 caspase-3(cleaved caspase-3)和 B 细胞淋巴瘤/白血病-2基因相关 X 蛋白(Bax)蛋白表达水平,验证其在信号通路中的关键作用.结果表明,与模型组相比,RGS 不同剂量组、肺宁片组和地塞米松组小鼠 BALF 中 WBC、EOS、NEU、LYM 数目均下降,BALF 中 IL-4、IL-5、IL-13 以及血清中 IgE、TNF-α 和 IL-1β 水平均显著降低,肺部炎性细胞浸润、气道壁增厚和黏液分泌明显减轻;RGS 不同剂量组肺组织中 p-ERK1/2、p-JNK、p-p38、p-NF-κB、p-IκBα 水平及 cleaved caspase-3、Bax 蛋白水平均下降.综上,RGS 可能通过调控 MAPK/NF-κB 信号通路抑制炎症反应和细胞凋亡,缓解小鼠气道炎症.
The aim of this paper was to explore the effect and mechanism of Regan Saibisitan Granules(RGS)on improving airway inflammatory responses in asthmatic mice by regulating the mitogen-activated protein kinase(MAPK)/nuclear factor-κB(NF-κB)signaling pathway.Female Balb/c mice were randomly divided into a blank group,a model group,low-,medium-and high-dose RGS groups(0.75,1.5,and 3 g·kg-1),dexamethasone group(3 mg·kg-1),and a Feining Tablets group(0.72 g·kg-1)according to body weight.The asthma model was established by ovalbumin(OVA)sensitization combined with aerosol challenge.The numbers of white blood cells(WBC),eosinophils(EOS),neutrophils(NEU),and lymphocytes(LYM)in bronchoalveolar lavage fluid(BALF)were counted.The levels of interleukin-4(IL-4),interleukin-5(IL-5),interleukin-13(IL-13),interferon-γ(INF-γ)in BALF,as well as the secretion of immunoglobulin E(IgE),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)in serum,were detected using enzyme-linked immunosorbent assay(ELISA)kits.The pathological changes of lung tissue were observed by hematoxylin-eosin and periodic acid-Schiff staining to comprehensively evaluate the ameliorative effect of RGS on inflammation in asthmatic mice.The protein expression levels of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2),phosphorylated c-Jun N-terminal kinase(p-JNK),phosphorylated mitogen-activated protein kinase(p-p38),phosphorylated NF-κB(p-NF-κB),phosphorylated inhibitor of NF-κB α(p-IκBα),cleaved caspase-3 and B-cell lymphoma/leukemia-2-associated X protein(Bax)in lung tissue were detected by Western blot.The results showed that compared with the model group,the numbers of WBC,EOS,NEU and LYM in BALF of the RGS groups,the Feining Tablets group and the dexamethasone group decreased,and the content of IL-4,IL-5,IL-13 in BALF as well as the levels of IgE,TNF-α and IL-1β in serum significantly decreased.In addition,inflammatory cell infiltration,airway wall thickening,and mucus secretion were significantly alleviated,and the levels of p-ERK1/2,p-JNK,p-p38,p-NF-κB,p-IκBα,as well as the protein levels of cleaved caspase-3 and Bax in lung tissue of the RGS groups decreased.In conclusion,RGS may inhibit inflammatory response and cell apoptosis by regulating the MAPK/NF-κB signaling pathway,thereby alleviating airway inflammation in asthmatic mice.
高慧敏;王玥;林明宝;徐磊;苏文灵;邢建国;郑瑞芳
石河子大学 药学院,新疆 石河子 832003新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830004中国医学科学院 药物研究所,北京 100050新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830004新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830004新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830004新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830004
哮喘热感赛比斯坦颗粒MAPK/NF-κB通路气道炎症
asthmaRegan Saibisitan GranulesMAPK/NF-κB pathwayairway inflammation
《中国中药杂志》 2026 (18)
5208-5215,8
新疆维吾尔自治区天山英才-科技创新领军人才项目(2023TSYCLJ0042)新疆维吾尔自治区重大科技专项(2022294474-4-2,2022A03017-2-4)新疆维吾尔自治区公益性科研院所基本科研业务费项目(KY2024122)中国医学科学院中央级公益性科研院所基本科研业务费专项(2024-RW350-01)
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