银杏内酯A通过p38MAPK通路减轻中性粒细胞性哮喘小鼠气道炎症  

Ginkgolide A relieving airway inflammation in a murine model of neutrophil predominant airway inflammation via suppression p38MAPK pathway

作　　者：王蓓蓓 徐芳[1] 王爱利 WANG Bei-bei;XU Fang;WANG Ai-li(Department of Respiratory,Wuhan No.1 Hospital,Wuhan,Hubei 430030,China)

机构地区：[1]武汉市第一医院呼吸内科,湖北武汉430030

出　　处：《临床肺科杂志》2021年第1期45-50,共6页Journal of Clinical Pulmonary Medicine

基　　金：武汉市卫计委科研计划资助项目(No.WZ17C03)。

摘　　要：目的探索银杏内酯A(Ginkgolide A,GA)对中性粒细胞为主的哮喘小鼠气道炎症的影响及可能的机制。方法28只雌性BALB/c小鼠随机分为对照组、哮喘组、GA干预组、地塞米松(dexamethasone,DEX)干预组,每组7只。哮喘组于第0、14、21天给予20ug卵清蛋白(ovalbumin,OVA)+75ul氟氏制剂(complete Freund’s adjuvant,CFA)腹腔注射致敏,第22-24天连续3天5%OVA雾化激发,对照组给予PBS致敏与激发。GA干预组及DEX干预组分别在每次激发前1小时给予80mg/kg GA及1mg/kg DEX腹腔注射。末次激发24小时后,对各组小鼠进行肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中细胞总数及细胞分类计数,检测BALF中超氧化物歧化酶(superoxide dismutase,SOD)水平、肺组织中p-ERK、p-p38、p-p85的蛋白水平,并对各组小鼠肺组织病理学特征进行评价。结果与对照组比较,哮喘组小鼠BALF中细胞总数及中性粒细胞计数均明显增加、SOD水平明显下降,气道粘液分泌及周围炎症细胞聚集明显加重,肺组织中p-p38蛋白表达水平明显升高,差异具有统计学意义(P<0.05)。经银杏内酯A干预后,哮喘小鼠BALF中细胞总数及中性粒细胞计数明显减少、气道粘液分泌及气道周围炎症细胞聚集明显减轻,BALF中SOD水平明显升高,同时肺组织中p-p38的表达水平明显下降,差异具有统计学意义(P<0.05)。经地塞米松干预组,上述指标变化不明显(P>0.05)。结论银杏内酯A可减轻中性粒细胞为主的哮喘小鼠气道周围炎症及氧化应激过程,其作用机制与p38丝裂原激活蛋白激酶(p38 Mitogen-activated protein kinase,p38MAPK)通路有关,可作为中性粒细胞为主的哮喘的有效治疗药物。Objective To explore the effect of Ginkgolide A(GA)on airway inflammation in neutrophil-predominant asthmatic mice and its possible mechanism.Methods 28 female BALB/c mice were randomly divided into the control group,the asthma group,the GA intervention group and the dexamethasone(DEX)intervention group,with 7 mice in each group.The asthma group was sensitized by intraperitoneal injection of 20 ug ovalbumin(OVA)+75 ul of CFA on Day 0,14,and 21,and stimulated with 5%OVA aerosolization on Day 22-24 continuously.The mice in the control group were sensitized and stimulated with PBS.The GA intervention group and the DEX intervention group was given 80 mg/kg GA or 1 mg/kg DEX respectively 1 hour before each challenge.After 24 hours of the last challenge,the total number of cells and cell counts,the level of superoxide dismutase(SOD)in alveolar lavage fluid(BALF),the content of p-ERK,p-p85 p-p38 in lung tissue,and the pathological features of lung tissue in each group were evaluated.Results Compared with the control group,the total number of cells and neutrophil count in BALF of the asthma group increased significantly,SOD level obviously decreased,mucus secretion and inflammatory cell around airway aggravated visibly,and the protein expression of p-p38 in lung tissue significantly increased(P<0.05).After intervention with ginkgolide A,the total number of cells and neutrophil counts in BALF of asthmatic mice were significantly reduced,airway mucus secretion and inflammatory cell aggregation around the airway were alleviated,SOD levels in BALF were significantly increased,and the expression of p-p38 was significantly decreased(P<0.05).However,in the dexamethasone intervention group,the changes of the above indicators were not significant(P>0.05).Conclusion Ginkgolide A can alleviate the inflammation and oxidative stress of the airway in neutrophil-predominant asthmatic mice,and the p38MAPK pathway maybe involved in the process,so it can be used as an effective treatment for neutrophil-predominant asthma.

关 键 词：银杏内酯A P38MAPK 哮喘 气道炎症 超氧化物歧化酶 

分 类 号：R285.5[医药卫生—中药学]