SB239063通过抑制TNF-α和p38MAPK,减轻香烟烟雾暴露变应性鼻炎大鼠MKP-1的表达  

SB239063 Attenuates the Expression Level of MKP-1 Via Suppressing TNF-αand p38MAPK in Rats with Allergic Rhinitis Exposured to Cigarette Smoke

作　　者：左晶晶[1] 陈金辉[1] 明伟[1] 王燕[1] 陶泽璋[1] 李紫荆 ZUO Jing-jing;CHEN Jin-hui;MING Wei;WANG Yan;TAO Ze-zhang;LI Zi-jing(Department of Otolaryngology-Head and Neck Surgery,Renmin Hospital of Wuhan University,Wuhan,Hubei,430060,China)

机构地区：[1]武汉大学人民医院耳鼻咽喉头颈外科,湖北武汉430060

出　　处：《现代生物医学进展》2022年第24期4612-4617,4605,共7页Progress in Modern Biomedicine

基　　金：中央高校基本科研业务费专项基金项目(2042019kf0084);国家自然科学基金项目(81870705,81670910)。

摘　　要：目的:探讨p38MAPK抑制剂SB239063对香烟烟雾暴露变应性鼻炎大鼠p38MAPK信号通路、TNF-α、MKP-1表达的影响。方法:先构建变应性鼻炎(AR)大鼠模型,然后给予AR大鼠被动吸入香烟烟雾(CS),再行腹腔注射AR大鼠SB239063(100mg/kg),分为AR组、AR+CS组、AR+CS+SB239063组。造模后对各组大鼠进行症状学评分;苏木精-伊红(HE)染色法观察大鼠鼻黏膜的形态学变化;实时荧光定量PCR(RT-PCR)检测鼻黏膜p38MAPK、MKP-1 m RNA的表达水平;酶联免疫吸附试验(ELISA)分析外周血、脾脏TNF-α的含量;Western blots检测鼻黏膜p38MAPK、p-p38MAPK、MKP-1蛋白的表达水平。结果:与AR组比较,AR+CS组大鼠的过敏症状(P<0.05)加重;鼻黏膜嗜酸性粒细胞(P<0.05)、中性粒细胞浸润(P<0.01)增多;MKP-1m RNA及其蛋白的表达水平均升高(P<0.001);外周血、脾脏TNF-α的表达水平升高(P<0.001);p-p38MAPK蛋白的表达水平升高(P<0.001)。与AR+CS组比较,AR+CS+SB239063组大鼠过敏症状评分下降(P<0.01);鼻黏膜中嗜酸性粒细胞、中性粒细胞计数下降(P值均<0.05);p38MAPK m RNA的表达水平降低(P<0.05),MKP-1 m RNA及其蛋白的表达水平下降(P<0.001);外周血、脾脏TNF-α的表达水平降低(P值均<0.001);p38MAPK、p-p38MAPK蛋白的表达水平降低,差异均具有显著统计学意义(P值均<0.001)。结论:SB239063通过抑制TNF-α、p38MAPK及其自磷酸化,减轻香烟烟雾暴露变应性鼻炎大鼠MKP-1的表达。Objective:To investigate the effects of p38 MAPK inhibitor SB239063 on p38 MAPK signal pathway,TNF-αand MKP-1 in cigarette smoke exposed allergic rhinitis(AR)rats.Methods:The AR model of rats was firstly established,and then was given passive inhalation of cigarette smoke(CS),and then was injected intraperitoneally with SB239063(100 mg/kg).They were divided into AR group,AR+CS group and AR+CS+SB 239063 group.After modeled,the rats in each group were scored by symptomatology;The morphological changes in nasal mucosa of rats were observed by hematoxylin eosin(HE)staining;The expression levels of p38MAPK and MKP-1 m RNA in nasal mucosa were detected by real-time fluorescence quantitative PCR(RT-PCR);TNF-αin peripheral blood and spleen was analyzed by enzyme-linked immunosorbent assay(ELISA);The expression levels of p38MAPK,p-p38MAPK and MKP-1proteins in nasal mucosa were detected by Western blots.Results:Compared with AR group,the allergic symptoms of AR+CS group were aggravated(P<0.05);Eosinophils infiltration(P<0.05)and neutrophil infiltration(P<0.01)in nasal mucosa were increased;The expression levels of MKP-1 m RNA and its protein were increased(P<0.001);The expression level of TNF-αin the peripheral blood and spleen were increased(P<0.001);The expression level of P-P38MAPK protein was increased(P<0.001).Compared to AR+CS group,the score of allergic symptoms in AR+CS+SB 239063 group was decreased(P<0.01);The counts of eosinophils and neutrophils in nasal mucosa were decreased(P<0.05);The expression level of p38MAPK m RNA was decreased(P<0.05),and the expression level of MKP-1 m RNA and its protein were decreased(P<0.001);The expression of TNF-αin the peripheral blood and spleen were decreased(P<0.001);The expression of p38MAPK protein and p-p38MAPK protein were decreased,and the difference was statistically significant(P<0.001).Conclusions:SB239063 reduced the expression level of MKP-1 via inhibiting TNF-α,p38MAPK and its autophosphorylation in rats with allergic rhinitis exposured to cigarette smoke.

关 键 词：变应性鼻炎 香烟烟雾 p38有丝分裂原活化蛋白激酶 炎症 抑制剂 

分 类 号：R-33[医药卫生] R765.21