左晶晶,陈金辉,明 伟,王 燕,陶泽璋,李紫荆.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[J].,2022,(24):4612-4617 |
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-α and p38MAPK in Rats with Allergic Rhinitis Exposured to Cigarette Smoke |
投稿时间:2022-04-30 修订日期:2022-05-28 |
DOI:10.13241/j.cnki.pmb.2022.24.003 |
中文关键词: 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 |
英文关键词: Allergic rhinitis Cigarette smoke p38MAPK Inflammation Inhibitor |
基金项目: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) |
|
摘要点击次数: 693 |
全文下载次数: 378 |
中文摘要: |
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(100 mg/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 mRNA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-1 mRNA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 mRNA的表达水平降低(P<0.05),MKP-1 mRNA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。 |
英文摘要: |
ABSTRACT Objective: To investigate the effects of p38 MAPK inhibitor SB239063 on p38 MAPK signal pathway, TNF-α and 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 mRNA in nasal mucosa were detected by real-time fluorescence quantitative PCR (RT-PCR); TNF-α in peripheral blood and spleen was analyzed by enzyme-linked immunosorbent assay (ELISA); The expression levels of p38MAPK, p-p38MAPK and MKP-1 proteins 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 mRNA and its protein were increased (P<0.001); The expression level of TNF-α in 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 mRNA was decreased (P<0.05), and the expression level of MKP-1 mRNA and its protein were decreased (P<0.001); The expression of TNF-α in 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). Conclusion: 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. |
查看全文
查看/发表评论 下载PDF阅读器 |
关闭 |