异钩藤碱对哮喘小鼠气道炎症的影响
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篇名: 异钩藤碱对哮喘小鼠气道炎症的影响
TITLE: Impacts of isorhynchophylline on airway inflammation in asthmatic mice
摘要: 目的 探讨异钩藤碱(IRN)调节单核细胞趋化蛋白1(MCP-1)/CC趋化因子受体2(CCR2)信号通路对哮喘小鼠气道炎症的影响。方法通过注射和吸入卵清蛋白的方法建立哮喘小鼠模型,将造模成功后的小鼠随机分为哮喘组、IRN低剂量组(IRN-L组,灌胃10mg/kgIRN)、IRN高剂量组(IRN-H组,灌胃20mg/kgIRN)、IRN-H+CCL2组[灌胃20mg/kgIRN+腹腔注射7.5ngCC趋化因子配体(CCL2)]、阳性对照组(腹腔注射2mg/kg地塞米松),并以注射和吸入无菌磷酸盐缓冲液的小鼠为空白对照组,每组10只。各药物组小鼠每天给予相应药物1次,连续给药2周。检测各组小鼠气道高反应指标——呼吸间歇(Penh)值,血清中肿瘤坏死因子α(TNF-α)、白细胞介素13(IL-13)、IL-4水平,支气管肺泡灌洗液中嗜酸性粒细胞(EOS)、淋巴细胞(LYM)和中性粒细胞(NEU)数量,肺组织中MCP-1、CCR2蛋白表达水平;观察肺组织病理学变化并进行炎症细胞浸润评分。结果与空白对照组比较,哮喘组小鼠肺组织炎症细胞浸润较明显,并有细胞肿胀、脱落现象发生;炎症细胞浸润评分,Penh值,IL-4、IL-13、TNF-α水平,EOS、NEU、LYM数量和MCP-1、CCR2蛋白表达水平均显著增加或升高(P<0.05);与哮喘组比较,IRN-L组、IRN-H组、阳性对照组小鼠肺组织病理损伤得到改善,上述定量指标均显著降低(P<0.05);与IRN-L组比较,IRN-H组、阳性对照组上述定量指标均显著降低(P<0.05);IRN-H组与阳性对照组比较,上述定量指标差异均无统计学意义(P>0.05);与IRN-H组比较,IRN-H+CCL2组上述定量指标均显著增加或升高(P<0.05),CCL2逆转了高剂量IRN对哮喘小鼠的保护作用。结论IRN可能通过抑制MCP-1/CCR2信号通路的激活来减少哮喘小鼠气道炎症因子的释放,从而达到改善哮喘的目的。
ABSTRACT: OBJECTIVE To investigate the impacts of isorhynchophylline (IRN) on airway inflammation in asthmatic mice by regulating the monocyte chemotactic protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2) signaling pathway. METHODS The asthmatic mice model was established by injecting and inhaling ovalbumin. The successfully modeled mice were randomly grouped into asthma group, IRN low-dose group (IRN-L, intragastric administration of 10 mg/kg IRN), IRN high-dose group (IRN-H, intragastric administration of 20 mg/kg IRN), IRN-H+CCL2 group [intragastric administration of 20 mg/kg IRN+intraperitoneal injection of 7.5 ng CC chemokine ligand 2 (CCL2)] and positive control group (intraperitoneal injection of 2 mg/kg dexamethasone). The mice injected and inhaled with sterile phosphate-buffered solution were included in the blank control group, with 10 mice in each group. The mice in administration groups were given relevant medicine once a day, for consecutive 2 weeks. The levels of airway hyperreactivity indexes such as enhanced (Penh) value, tumor necrosis factor-α (TNF-α),interleukin-13 (IL-13) and IL-4 in serum, the number of eosinophil (EOS), lymphocyte (LYM) and neutrophils (NEU) in alveolar lavage fluid and the protein expressions of MCP-1 and CCR2 in lung tissue were observed in each group; the pulmonary histopathological changes were observed, and inflammatory cell infiltration score was evaluated. RESULTS Compared with the blank control group, the infiltration of inflammatory cells in the lung tissue of mice was more significant in the asthma group, and there was swelling and shedding of cells; inflammatory infiltration score, Penh value, the levels of IL-4, IL-13 and TNF-α, the number of EOS, NEU and LYM, the protein expressions of MCP-1 and CCR2 were increased significantly (P<0.05). Compared with the asthma group, the pathological injuries of the IRN-L group, IRN-H group and positive control group were improved, and the above quantitative indexes were decreased significantly (P<0.05). Compared with the IRN-L group, the above quantitative indexes of the IRN-H group and positive control group were decreased significantly (P<0.05). There was no statistical significance in the above quantitative indexes between the IRN-H group and the positive control group (P>0.05). Compared with the IRN-H group, the above quantitative indexes of the IRN-H+CCL2 group were increased significantly (P<0.05). CCL2 reversed the protective effect of high-dose IRN on asthmatic mice. CONCLUSIONS IRN may reduce the release of airway inflammatory factors in asthmatic mice by inhibiting the activation of the MCP-1/CCR2 signaling pathway, so as to achieve the purpose of improving asthma.
期刊: 2023年第34卷第22期
作者: 蔡金;华诏召;张昌容;黄丹;张淇华;王毅;周素芳;刘莲;龚安
AUTHORS: CAI Jin,HUA Zhaozhao, ZHANG Changrong,HUANG Dan,ZHANG Qihua,WANG Yi,ZHOU Sufang,LIU Lian,GONG An
关键字: 异钩藤碱;哮喘;单核细胞趋化蛋白1/CC趋化因子受体2信号通路;气道炎症
KEYWORDS: isorhynchophylline; asthma; monocyte chemotactic protein-1/CC chemokine receptor 2 signaling pathway; airway
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