Calpeptin通过抑制GATA3减轻变应性鼻炎大鼠炎症

摘要 目的：本研究旨在评估钙蛋白酶抑制剂calpeptin减轻变应性鼻炎大鼠炎症的作用并探讨其机制。方法：将20只雄性SD大鼠采用数字表法随机分为4组：正常组（Normal）、变应性鼻炎组（AR）、地塞米松干预AR组（DXMS+AR）、calpeptin干预AR组（Calpeptin+AR）。造模成功后，对大鼠AR症状进行行为学评分，对大鼠鼻黏膜组织切片以HE和PAS染色法观察鼻黏膜病理改变；对大鼠外周血以ELISA法检测总IgE、IL-4、IL-13水平；对大鼠鼻黏膜组织以免疫蛋白印迹法检测GATA3蛋白表达水平。单因素方差分析进行多组间比较，LSD- t检验进行组间两两比较。结果：与Normal组相比，AR组大鼠的鼻部过敏症状、鼻黏膜嗜酸粒细胞计数及外周血总IgE水平均升高，Calpeptin与地塞米松均能减轻气道炎症，减少嗜酸性粒细胞浸润，降低血清中OVA诱导的IgE的生成。探讨机制发现，酶联免疫吸附试验检测Th2细胞因子，与Normal组比较，AR组血清IL-4、IL-13水平均升高（P＜0.05），而Calpeptin与地塞米松均能降低血清IL-4、IL-13水平（P＜0.05）。免疫蛋白印迹法检测大鼠鼻黏膜GATA3蛋白表达水平显示，与Normal组比较，AR组鼻黏膜 GATA3表达升高（P＜0.05），而Calpeptin与地塞米松组鼻黏膜 GATA3表达均下降（P＜0.05）。结论：腹腔注射calpeptin能够减轻变应性鼻炎大鼠局部和全身过敏反应，其机制可能下调GATA3表达，影响Th2细胞的分化及细胞因子的分泌有关。

Calpeptin Alleviates Inflammation in Rats with Allergic Rhinitis by Inhibiting GATA3

ABSTRACT Objective: The purpose of this study was to evaluate the therapeutic effect of calpeptin on allergic rhinitis rats and to explore its mechanism. Methods: Twenty rats were randomly divided into four groups: normal group (normal), allergic rhinitis group (AR), dexamethasone intervention AR group (DXMS + AR), calpeptin intervention AR group (calpeptin + AR). After the establishment of rat model in each group, the behavior score of AR symptoms was carried out, and the pathological changes of nasal mucosa were observed by Hematoxylin eosin (HE) and Periodic acid-Schiff (PAS) staining. The levels of total IgE, IL-4 and IL-13 in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). The expression level of GATA3 in rat nasal mucosa was detected by Western blot. One way ANOVA was used for multi group comparison, and LSD-t test was used for pairwise comparison. Results: The nasal allergic symptoms, eosinophil count of nasal mucosa and total IgE level of peripheral blood in AR group were higher than those in normal group. Both calpeptin and dexamethasone can reduce airway inflammation, eosinophil infiltration and ova induced IgE production in serum. It was further found that compared with Normal group, the levels of serum IL-4 and IL-13 in AR group increased (P<0.05), while calpeptin and dexamethasone decreased (P<0.05). Western blot showed that compared with normal group, the expression of GATA3 in AR group increased (P<0.05), while the expression of GATA3 in calpeptin and dexamethasone decreased (P<0.05). Conclusion: Intraperitoneal injection of calpeptin can alleviate local and systemic anaphylaxis in allergic rhinitis rats, and its mechanism may be related to down regulating the expression of GATA3 and affecting the differentiation of Th2 cells and the secretion of Th2 cytokines.