摘要
目的探讨川芎嗪调节TGF-β/Smad信号通路对哮喘小鼠的气道炎症和气道重塑的影响及其作用机制。方法选取40只健康雌性BALB/c小鼠,随机分为对照、模型、川芎嗪、地塞米松组,每组各10只。采用卵清白蛋白(OVA)+氢氧化铝混合液腹腔注射致敏、OVA滴鼻激发构建小鼠慢性哮喘模型,在激发同时川芎嗪、地塞米松组小鼠分别于每日滴鼻激发前30 min ip川芎嗪注射液80 mg/kg或地塞米松注射液2 mg/kg,模型组小鼠ip等量生理盐水。小鼠处死后取肺组织行HE染色观察评估肺组织病理变化,Masson染色观察评估小鼠肺组织气道重塑,ELISA法检测血清中免疫球蛋白E(IgE)、白细胞介素-5(IL-5)、转录因子GATA-3及转化生长因子-β(TGF-β)表达水平,免疫印迹法检测小鼠肺组织中TGF-β1和Smad2、Smad7表达水平。结果与模型组比较,川芎嗪组小鼠气道改变明显减轻,气管壁炎性细胞浸润减少,气道壁、平滑肌层和基底膜层增厚减轻。川芎嗪组气道周围炎症和肺泡炎症评分显著降低(P<0.05)。川芎嗪组基底膜层、平滑肌层厚度明显降低,气道壁内外径比值明显升高(P<0.05)。川芎嗪组小鼠血清中IgE、IL-5、GATA-3和TGF-β1水平明显降低(P<0.05)。川芎嗪组小鼠肺组织中TGF-β1、Smad2表达均降低,而Smad7表达增加(P<0.05)。结论川芎嗪可改善哮喘小鼠气道重塑,其机制是通过调节TGF-β/Smad信号通路来实现的。
Objective To investigate the effect of ligustrazine on airway inflammation and airway remodeling in mice asthma models by regulating TGF-β/Smad signaling pathway and explore its mechanism. Methods Healthy female BALB/c mice were randomly divided into control group, model group, ligustrazine group, and dexamethasone group, and each group had 10 mice. The model was established by ip OVA + Al2(OH)3 mixture, and nasal instillation of OVA. Mice in the ligustrazine and dexamethasone groups were ip administered with Ligustrazine Injection 80 mg/kg, or Dexamethasone Injection 2 mg/kg 30 min before nasal instillation. Mice in model group were ip with the same amount of saline. Pathological changes of lung tissue in mice were observed by HE staining, airway remodeling in lung tissue of mice were observed by Masson staining, the levels of IgE, IL-5, GATA-3, and TGF-β1 in serum were detected by ELISA, and the expression levels of TGF-β1, Smad2, and Smad7 in lung tissue of mice were detected by Western blotting method. Results Compared with the model group, the airway changes were significantly relieved, the infiltration of inflammatory cells in tracheal wall of mice in the ligustrazine group were reduced, and the thickening of airway wall, smooth muscle layer, and basement membrane were decreased. Compared with the model group, the scores of airway inflammation and alveolar inflammation of mice in the ligustrazine group were significantly reduced(P < 0.05). Compared with the model group, the ratio of inner and outer diameter of the airway wall of mice in the ligustrazine group was significantly increased(P < 0.05). Compared with the model group, serum IgE, IL-5, GATA-3 and TGF-β1 levels in the ligustrazine and dexamethasone groups were significantly reduced(P < 0.05). Compared with the model group, the expressions of TGF-β1 and Smad2 in lung tissues of mice in the ligustrazine group were decreased, but the expressions of Smad7 were increased(P < 0.05). Conclusions Ligustrazine can improve airway remodeling in asthma by regulating the TGF-β/Smad signaling pathway.
作者
史雅旭
戴曦
王丽娇
伍娟
江山
杨小琼
SHI Ya-xu;DAI Xi;WANG Li-jiao;WU Juan;JIANG Shan;YANG Xiao-qiong(Department of Respiratory, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China;Department of Respiratory, Meishan City People’s Hospital, Meishan 620010, China;Department of Respiratory, the Second Chinese Medicine Hospital of Sichuan Province, Chengdu 610000, China;Department of Respiratory and Critical Care Medicine, Dujiangyan People’s Hospital, Chengdu 611830, China)
出处
《现代药物与临床》
CAS
2019年第1期20-26,共7页
Drugs & Clinic
作者简介
史雅旭,女,呼吸内科硕士研究生,研究方向哮喘。E-mail:503377684@qq.com;通信作者:杨小琼,副教授。E-mail:596635352@qq.com,
