| 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].现代生物医学进展英文版,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 |
| Received:April 30, 2022 Revised:May 28, 2022 |
| 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） |
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| 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. |
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