首页|射干麻黄汤对支气管哮喘大鼠巨噬细胞活化及IL-21/STAT3通路调节作用研究

射干麻黄汤对支气管哮喘大鼠巨噬细胞活化及IL-21/STAT3通路调节作用研究

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目的 探讨射干麻黄汤对支气管哮喘大鼠巨噬细胞活化及白细胞介素(IL)-21/信号转导和转录活化因子3(STAT3)通路调节作用.方法 取雄性SD大鼠36 只,随机选择6 只作为正常组,其余大鼠采用卵清白蛋白致敏法建立支气管哮喘模型.将造模成功大鼠随机分为哮喘组、射干麻黄汤低剂量组、射干麻黄汤中剂量组、射干麻黄汤高剂量组及地塞米松组,每组6 只.射干麻黄汤低、中、高剂量组大鼠分别给予1 g/kg、2 g/kg、4 g/kg(以生药含量计)射干麻黄汤灌胃,地塞米松组大鼠给予1 mg/kg地塞米松灌胃,正常组及哮喘组大鼠灌胃等量蒸馏水,均 1 次/d,连续灌胃20 d.末次灌胃结束后,使用肺功能检测系统测定大鼠肺活量、肺动态顺应性及呼气峰值流速,ELISA法测定肺泡灌洗液中干扰素-γ(IFN-γ)、IL-2、IL-4、IL-13 水平,计算肺泡灌洗液中嗜酸性粒细胞及中性粒细胞占比,HE染色法观察肺组织病理学形态,免疫组化法观察肺组织中F4/80 蛋白阳性表达情况,Western blot法测定肺组织中IL-21、p-STAT3、STAT3 蛋白表达情况.结果 与正常组比较,哮喘组大鼠肺活量、肺动态顺应性、呼气峰值流速及肺泡灌洗液中IFN-γ、IL-2 水平均明显降低(P均<0.05),肺泡灌洗液中嗜酸性粒细胞占比、中性粒细胞占比、IL-4 水平、IL-13 水平及肺组织中F4/80 蛋白阳性表达相对积分光密度和IL-21 蛋白相对表达量、p-STAT3/STAT3 比值均明显升高(P均<0.05),肺组织炎症损伤.与哮喘组比较,射干麻黄汤各组及地塞米松组大鼠肺活量、肺动态顺应性、呼气峰值流速及肺泡灌洗液中IFN-γ、IL-2 水平均明显升高(P均<0.05),肺泡灌洗液中嗜酸性粒细胞占比、中性粒细胞占比、IL-4 水平、IL-13 水平及肺组织中F4/80 蛋白阳性表达相对积分光密度和IL-21 蛋白相对表达量、p-STAT3/STAT3 比值均明显降低(P均<0.05),肺组织病理改变明显恢复,且各指标随射干麻黄汤剂量的增加改善更明显.结论 射干麻黄汤能够显著改善支气管哮喘大鼠肺功能,缓解气道炎症反应,减轻肺组织病变,其机制可能与抑制肺组织巨噬细胞活化、调节IL-21/STAT3 通路有关.
Effect of Decoction of Belamcanda Rhizome and Ephedra on activation of macrophage and regulation of IL-21/STAT3 pathway in rats with bronchial asthma
Objective It is to explore the effect of Decoction of Belamcanda Rhizome and Ephedra on activation of mac-rophage and regulation of IL-21/STAT3 pathway in rats with bronchial asthma.Methods Thirty-six male SD rats were taken,in which 6 rats were randomly selected as the normal group,and the rest of the rats were used to establish bronchial asthma models by ovalbumin sensitization method.The successfully modeled rats were randomly divided into asthma group,low-dose,medium-dose and high-dose groups of Decoction of Belamcanda Rhizome and Ephedra and dexamethasone group,with 6 rats in each group.The rats in the low-dose,medium-dose and high-dose groups of Decoction of Belamcanda Rhizo-me and Ephedra were given 1 g/kg,2 g/kg and 4 g/kg of Decoction of Belamcanda Rhizome and Ephedra(according to raw drug content)by gavage,the rats in the dexamethasone group were given 1 mg/kg of dexamethasone by gavage,and the rats in the normal group and asthma group were gavaged with the same amount of distilled water,all once daily,contin-uously treated for 20 days.At the end of the final gavage,the lung capacity,lung dynamic compliance and peak expiratory flow rate of the rats were detected by a lung function test system,the levels of interferon-γ(IFN-γ),IL-2,IL-4,and IL-13 in alveolar lavage fluid were detected by ELISA,the percentages of eosinophils and neutrophils in alveolar lavage fluid were calculated,the pathological morphology of lung tissues was observed by HE staining,the positive expression of F4/80 protein in lung tissues was detected by immunohistochemistry,and the positive expressions of IL-21,p-STAT3,and STAT3 proteins in lung tissues were detected by Western blot.Results Compared with the normal group,the lung capacity,dy-namic lung compliance,peak expiratory flow rate,the levels of INF-γ and IL-2 in alveolar lavage fluid of rats in the asthma group were significantly decreased(all P<0.05),the percentages of eosinophils and neutrophils in alveolar lavage fluid,and the levels of IL-4 and IL-13 in lung tissue,and the integral optical density of relative expression of F4/80 protein,rela-tive expressions of IL-21 in lung tissue and P-STAT3/STAT3 were significantly increased(all P<0.05),inflammatory in-jury of lung tissue was found.Compared with the asthma group,the lung capacity,dynamic lung compliance,peak expira-tory flow rate,the levels of INF-γ and IL-2 in alveolar lavage fluid of rats in each dose group of Decoction of Belamcanda Rhizome and Ephedra and dexamethasone group were significantly increased(all P<0.05),the percentages of eosinophils and neutrophils in alveolar lavage fluid,and the levels of IL-4 and IL-13 in lung tissue,and the integral optical density of relative expression of F4/80 protein,relative expressions of IL-21 in lung tissue and P-STAT3/STAT3 were significantly decreased(all P<0.05),the inflammatory injury of lung tissue was significantly improved,and the improvements of these indexes were more significant with the increase of dose of Decoction of Belamcanda Rhizome and Ephedra.Conclusion De-coction of Belamcanda Rhizome and Ephedra can significantly improve lung function,relieve airway inflammation,improve lung tissue lesions in bronchial asthma rats,which may be related to inhibit activation of macrophage and regulate IL-21/STAT3 pathway.

Decoction of Belamcanda Rhizome and Ephedrabronchial asthmamacrophage activationIL-21/STAT3 pathway

张凤凯、张宏丽、杨卫立

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珠海市中西医结合医院,广东 珠海 519000

珠海市香湾社区卫生服务中心,广东 珠海 519000

支气管哮喘 射干麻黄汤 巨噬细胞活化 IL-21/STAT3通路

珠海市社会发展领域科技计划

2220004000254

2024

现代中西医结合杂志
中国中西医结合学会河北分会,中华中医药学会

现代中西医结合杂志

CSTPCD
影响因子:1.775
ISSN:1008-8849
年,卷(期):2024.33(5)
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