百合知母汤下调钙调神经磷酸酶表达从而抑制气道重塑
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摘要
目的:观察百合知母汤对钙调神经磷酸酶蛋白(CaN)的表达影响,探讨其抑制哮喘大鼠气道重塑的干预机制。方法:7周龄雄性Wistar大鼠随机分为对照组,模型组,百合知母汤低、中、高剂量组,地塞米松组,每组10只。10%卵白蛋白(OVA)溶液腹腔注射致敏,2%OVA溶液超声雾化吸入诱发哮喘发作,构建哮喘大鼠模型。HE染色法观察肺组织病理学改变;图像分析法检测支气管管壁厚度;生物化学法检测大鼠肺组织CaN活性;免疫组织化学检测CaN蛋白的表达。结果:与对照组比较,模型组支气管管壁结构破坏,大量炎性细胞浸润,支气管的厚度和肺组织CaN活性分别增加了43%及33%(P<0.01)。与模型组比较,药物干预后大鼠气道炎性反应得到不同程度地改善,各治疗组支气管管壁厚度以及肺组织CaN活性显著下降(P<0.05,P<0.01)。大鼠支气管管壁厚度与大鼠肺组织CaN活性呈正相关(P<0.01)。结论:百合知母汤能够减轻气道炎性反应,改变气道重组,与下调CaN的表达有关。
Objective:To observe the effects of Baihe Zhimu Decoction on the expression of calcineurin protein and to explore the mechanism of its intervention on the airway remodeling in asthmatic rats.Methods:Seven-week-old male Wistar rats were randomly divided into control group,model group,Baihe Zhimu Decoction low,medium and high dose groups and dexamethasone group.The rats were sensitized with 10% ovalbuminby intraperitoneal injection,then induced with 2% ovalbumin by ultrasonic atomizing inhalation to establish the asthma model.Pathological changes of lung tissue were observed by HE staining.The thickness of bronchial wall was evaluated by image analysis system.CaN activity in lung tissue was detected by biochemistry method and the expression of CaN protein was detected by immunohistochemistry.Results:Compared with the control group,the bronchial wall structure of the model group was destroyed,and large number of inflammatory cell infiltration,bronchial thickness and lung tissue CaN activity increased by 43%(P<0.01),33%(P<0.01).Compared with the model group,the airway inflammatory response in rats was improved to some extent after drug intervention.The bronchial wall thickness and the CaN activity of lung tissue in each treatment group were significantly decreased(P<0.05).There was a positive correlation between the level of the bronchial and the activation of CaN(P<0.05).Conclusion:Baihe Zhimu Decoction can reduce airway inflammatory response,alter airway remodeling,and down-regulate the expression of CaN.
Objective:To observe the effects of Baihe Zhimu Decoction on the expression of calcineurin protein and to explore the mechanism of its intervention on the airway remodeling in asthmatic rats.Methods:Seven-week-old male Wistar rats were randomly divided into control group,model group,Baihe Zhimu Decoction low,medium and high dose groups and dexamethasone group.The rats were sensitized with 10% ovalbuminby intraperitoneal injection,then induced with 2% ovalbumin by ultrasonic atomizing inhalation to establish the asthma model.Pathological changes of lung tissue were observed by HE staining.The thickness of bronchial wall was evaluated by image analysis system.CaN activity in lung tissue was detected by biochemistry method and the expression of CaN protein was detected by immunohistochemistry.Results:Compared with the control group,the bronchial wall structure of the model group was destroyed,and large number of inflammatory cell infiltration,bronchial thickness and lung tissue CaN activity increased by 43%(P<0.01),33%(P<0.01).Compared with the model group,the airway inflammatory response in rats was improved to some extent after drug intervention.The bronchial wall thickness and the CaN activity of lung tissue in each treatment group were significantly decreased(P<0.05).There was a positive correlation between the level of the bronchial and the activation of CaN(P<0.05).Conclusion:Baihe Zhimu Decoction can reduce airway inflammatory response,alter airway remodeling,and down-regulate the expression of CaN.
引文
[1]Jang H H,Cho S Y,Kim M J,et al.Anti-inflammatory effects of Salvia plebeia R.Br extract in vitro and in ovalbumin-induced mouse model.Biol Res,2016,49(1):41
[2]徐光星,何若苹,何任.百合病方证与临床—《金匮要略》方证与临床系列之四.浙江中医杂志,2009,44(5):313-315
[3]Shin I S,Lee M Y,Lim H S,et al.An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.PLo S One,2012,7(9):e45734
[4]李学良,许朝霞,钱鹏,等.宣肺固本中药对哮喘大鼠血清IL-17、IL-22的影响.中华中医药杂志,2014,29(2):598-601
[5]Yamaguchi M,Niimi A,Matsumoto H,et al.Sputum levels of transforming growth factor-β1 in asthma:relation to clinical and computed tomography findings.Investig Allergol Clin Immunol,2008,18(3):202-206
[6]Song L,Tang H,Liu D,et al.The Chronic and Short-Term Effects of Gefinitib on Airway Remodeling and Inflammation in a Mouse Model of Asthma.Cell Physiol Biochem,2016,38(1):194-206
[7]Shifren A,Witt C,Christie C,et al.Mechanisms of remodeling in asthmatic airways.J Allergy(Cairo),2012,2012:316049
[8]Park S,Chung HS,Shin D,et al.Adenovirus-mediated Foxp3expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model.Exp Mol Med,2016,48(9):e259
[9]Whie M,Montezano A C,Touyz R M.AngiotensinⅡsignaling and calcineurin in cardiac fibroblasts:differential effects of cacineurin inhibitors FK506 and cyclosporine A.Ther Adv Cardiovasc Dis,2012,6(1):5-14
[10]陈亚红,赵鸣武,符民桂,等.钙调神经磷酸酶在哮喘豚鼠气道重塑中的作用.中国病理生理杂志,2002,18(2):157-160
[11]李家邦.中医学.6版.北京:人民卫生出版社,2005:317-319
[12]孙丽平,王延博,冯晓纯,等.益气固本胶囊对脾气虚哮喘小鼠血清INF-γ及IL-4的影响.中华中医药杂志,2015,30(11):4068-4070
[13]马秀丽,安耀荣,邱桐.百合知母汤对哮喘大鼠血清、肺泡灌洗液中SP-A及脏器系数变化的影响.现代生物医学进展,2012,12(8):1423-1429
[14]孙婧,安耀荣,邱桐.百合知母汤对哮喘模型大鼠IL-4、IFN-γ含量和EOS计数的影响.甘肃中医学报,2011,28(2):12-15
[2]徐光星,何若苹,何任.百合病方证与临床—《金匮要略》方证与临床系列之四.浙江中医杂志,2009,44(5):313-315
[3]Shin I S,Lee M Y,Lim H S,et al.An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.PLo S One,2012,7(9):e45734
[4]李学良,许朝霞,钱鹏,等.宣肺固本中药对哮喘大鼠血清IL-17、IL-22的影响.中华中医药杂志,2014,29(2):598-601
[5]Yamaguchi M,Niimi A,Matsumoto H,et al.Sputum levels of transforming growth factor-β1 in asthma:relation to clinical and computed tomography findings.Investig Allergol Clin Immunol,2008,18(3):202-206
[6]Song L,Tang H,Liu D,et al.The Chronic and Short-Term Effects of Gefinitib on Airway Remodeling and Inflammation in a Mouse Model of Asthma.Cell Physiol Biochem,2016,38(1):194-206
[7]Shifren A,Witt C,Christie C,et al.Mechanisms of remodeling in asthmatic airways.J Allergy(Cairo),2012,2012:316049
[8]Park S,Chung HS,Shin D,et al.Adenovirus-mediated Foxp3expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model.Exp Mol Med,2016,48(9):e259
[9]Whie M,Montezano A C,Touyz R M.AngiotensinⅡsignaling and calcineurin in cardiac fibroblasts:differential effects of cacineurin inhibitors FK506 and cyclosporine A.Ther Adv Cardiovasc Dis,2012,6(1):5-14
[10]陈亚红,赵鸣武,符民桂,等.钙调神经磷酸酶在哮喘豚鼠气道重塑中的作用.中国病理生理杂志,2002,18(2):157-160
[11]李家邦.中医学.6版.北京:人民卫生出版社,2005:317-319
[12]孙丽平,王延博,冯晓纯,等.益气固本胶囊对脾气虚哮喘小鼠血清INF-γ及IL-4的影响.中华中医药杂志,2015,30(11):4068-4070
[13]马秀丽,安耀荣,邱桐.百合知母汤对哮喘大鼠血清、肺泡灌洗液中SP-A及脏器系数变化的影响.现代生物医学进展,2012,12(8):1423-1429
[14]孙婧,安耀荣,邱桐.百合知母汤对哮喘模型大鼠IL-4、IFN-γ含量和EOS计数的影响.甘肃中医学报,2011,28(2):12-15