雾化吸入抗NGF缓释微球抑制哮喘气道炎症的疗效探讨
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摘要
目的探讨哮喘小鼠雾化吸入抗神经生长因子(NGF)缓释微球(NGFM)对气道炎症的抑制作用。方法动物分为4组:对照组、哮喘组、抗NGF组和雾化抗NGFM组。卵蛋白诱导建立气道重塑模型;测定并评估网状基底膜厚度、胶原蛋白厚度和肺组织的气道壁厚度;HE、Masson和AB-PAS染色观察拮抗前、后肺部病理变化,免疫组织化学方法及RT-PCR分别检测小鼠拮抗前、后的肺内的NGF蛋白及mRNA表达变化。结果病理严重程度评分结果依次为哮喘组>抗NGF组>抗NGFM组。各组肺功能的平均气道阻力值依次为哮喘组>抗NGF组>抗NGFM组>对照组。NGF激发后的动态肺顺应值依次为对照组>抗NGFM组>抗NGF组>哮喘组。对气道平滑肌厚度、网状基底膜厚度、胶原蛋白厚度进行比较,抗NGFM组<抗NGF组<哮喘组、NGF蛋白和mRNA水平进行比较,对照组<哮喘组<抗NGF组<抗NGFM组间的差异均有统计学意义(P<0.05)。结论雾化吸入抗NGF缓释微球对哮喘小鼠气道炎症有抑制作用,并能改善肺功能。
Objective To explore atomization inhalation anti-nerve growth factor(anti-NGF)slow-release microspheres whether can inhibit the airway inflammation of asthma mice.Methods Animals were randomly divided into four groups:control group,asthma group,anti-NGF group,and anti-NGF slow-release microspheres(refer to anti-NGFM)group,10 mice in each group.We used OVA induced sensitization mice so as to establish the airway remodeling of asthma model mice.Detection and evaluation of the reticular basement membrane thickness,collagen and lung airway wall thickness were done.HE staining,Masson staining and AB-PAS staining was used to study the lung pathological changes after mice were antagonism,immunohistochemical method to detect and compare the NGF protein and mRNA expression of bronchial mucosa.Immunohistochemical method was used to detect NGF protein and mRNA expression change in the lungs before and after the mice were antagonism.Results According to the severity,the score for each group of pathology was in the order of anti-NGFM group>anti-NGF group>asthma group.Groups of average airway resistance value of the lung function were analyzed,resistance value was in the order of asthma group>anti-NGF group>antiNGFM group>the control group.Dynamic lung compliance of mice after histamine excitation generated by NGF was in the order of control group>anti-NGFM group>anti-NGF group> asthma group.The airway smooth muscle and reticular basement membrane thickness,collagen deposition was in the order of anti-NGFM group>anti-NGF group>asthma group and NGF protein and mRNA expression was control group
Objective To explore atomization inhalation anti-nerve growth factor(anti-NGF)slow-release microspheres whether can inhibit the airway inflammation of asthma mice.Methods Animals were randomly divided into four groups:control group,asthma group,anti-NGF group,and anti-NGF slow-release microspheres(refer to anti-NGFM)group,10 mice in each group.We used OVA induced sensitization mice so as to establish the airway remodeling of asthma model mice.Detection and evaluation of the reticular basement membrane thickness,collagen and lung airway wall thickness were done.HE staining,Masson staining and AB-PAS staining was used to study the lung pathological changes after mice were antagonism,immunohistochemical method to detect and compare the NGF protein and mRNA expression of bronchial mucosa.Immunohistochemical method was used to detect NGF protein and mRNA expression change in the lungs before and after the mice were antagonism.Results According to the severity,the score for each group of pathology was in the order of anti-NGFM group>anti-NGF group>asthma group.Groups of average airway resistance value of the lung function were analyzed,resistance value was in the order of asthma group>anti-NGF group>antiNGFM group>the control group.Dynamic lung compliance of mice after histamine excitation generated by NGF was in the order of control group>anti-NGFM group>anti-NGF group> asthma group.The airway smooth muscle and reticular basement membrane thickness,collagen deposition was in the order of anti-NGFM group>anti-NGF group>asthma group and NGF protein and mRNA expression was control group
引文
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[12]王世寿,武刚.肺部缓释微球治疗肺部疾病的性能及评价[J].中国组织工程研究,2013,17(12):2241-2248.
[2]YANG Y G,TIAN W M,ZHANG H,et al.Nerve growth factor exacerbates allergic lung inflammation and airway remodeling in a rat model of chronic asthma[J].Expand Ther Med,2013,6(5):1251-1258.
[3]HUANG L W,SUN G,WANG D L,et al.Inhibition of nerve growth factor/tyrosine kinase receptor A signaling ameliorates airway remodeling in chronic allergic airway inflammation[J].Eur Rev Med Pharmacol Sci,2015,19(12):2261-2268.
[4]MASAELI R,KASHI T S J,DINARVAND R,et al.Preparation,characterization and evaluation of drug release propertiesofsimvastatin-ioadedPLGA microspheres[J].Iran J Pharm Res,2016,15(Suppl):205-211.
[5]YUAN W,LIU Z.Controlled-release and preserved bioactivity of proteins from(self-assembled)core-shell doublewalled microspheres[J].Int J Nanomedicine,2012(1),7:257-270.
[6]佘巍巍,杨新官.哮喘大鼠肺内神经生长因子的表达变化及与病理改变的关系[J].西安交通大学学报(医学版),2012,33(1):65-67.
[7]佘巍巍,陈峰,罗淼.神经生长因子对哮喘大鼠气道炎症中TNF-α表达的调节作用[J].中国老年学杂志,2011,31(17):3301-3303.
[8]LIU Y,ZHANG B,ZHANG S,et al.Nerve growth factor mediated SH2-Bbeta/Akt signal pathway activated in allergic airway challenge in mice[J].Respirology,2010,15(1):80-87.
[9]FREUND V,PONS F,JOLY V,et al.Upregulation of nerve growth factor expression by human airway smooth muscle cells in inflammatory conditions[J].Eur Respir J,2002,20(2):458-463.
[10]HANF Y,THURECHTK J,WHITTAKERA K,et al.Bioerodable PLGA-based microparticles for producing sustained-release drug formulations and strategies for improving drug loading[J].Front Pharmacol,2016(7):185.
[11]JIANG W,GUPTA R K,DESHPANDE M C,et al.Biodegradable poly(lactic-co-glycolic acid)microparticle for injectable delivery of vaccine antigens[J].Adv Drug Deliv Rev,2005,57(3):391-410.
[12]王世寿,武刚.肺部缓释微球治疗肺部疾病的性能及评价[J].中国组织工程研究,2013,17(12):2241-2248.