熊果酸对变应性鼻炎大鼠Th1/Th2平衡等功能的影响  

Effects of ursolic acid on Th1/Th2 balance and other functions in rats with allergic rhinitis

作　　者：杨雪华[1] 马文新[1] 谭亚洲 郭向东[2] YANG Xuehua;MA Wenxin;TAN Yazhou;GUO Xiangdong(Department of Otolaryngology,Anyang District Hospital,Puyang 455000,China;the First Affiliated Hospital of He nan University of CM,Zhengzhou 450000,China)

机构地区：[1]濮阳市安阳地区医院耳鼻咽喉科,濮阳455000 [2]河南中医药大学第一附属医院,郑州450000

出　　处：《西北药学杂志》2023年第2期80-85,共6页Northwest Pharmaceutical Journal

基　　金：河南省医学科技攻关计划项目(编号:LHGJ20190194)。

摘　　要：目的 观察熊果酸对变应性鼻炎(allergic rhinitis, AR)大鼠Th1/Th2平衡及鼻黏膜嗜酸性粒细胞的影响,探究其作用机制。方法 将大鼠随机分为正常组,模型组,氯雷他定组(5 mg·kg^(-1)),熊果酸高、中、低剂量组(100、50和25 mg·kg^(-1)),每组10只。使用卵清蛋白建立大鼠AR模型,评估鼻部症状积分,用RT-qPCR法检测大鼠鼻黏膜白细胞介素-2(interleukin-2,IL-2)、干扰素-γ(interferon-γ,INF-γ)、白细胞介素-4(interleukin-4,IL-4)、白细胞介素-5(interleukin-5,IL-5)和嗜酸性粒细胞趋化因子(eosinophil activated chemotactic factor, Eotaxin)mRNA的表达水平,HE染色观察鼻黏膜病变,计数嗜酸性粒细胞(eosinophil granulocyte, EOS),用Western blot法检测大鼠TLR4/NF-κB信号通路蛋白的表达水平。结果 与正常组比较,模型组大鼠鼻部症状积分升高,鼻黏膜组织IL-2和INF-γ mRNA的表达水平显著降低,IL-4和IL-5 mRNA的表达水平上升,鼻黏膜上皮可见显著不连续,有较多EOS浸润,Eotaxin mRNA的表达水平显著升高,TLR4、MyD88和p-NF-κB p65蛋白的表达水平显著升高(P<0.05)。与模型组比较,熊果酸组大鼠鼻部症状积分降低,鼻黏膜组织IL-2和INF-γ mRNA的表达水平上升,IL-4和IL-5 mRNA的表达水平降低,鼻黏膜上皮细胞生长有序、结构完整,有少量EOS浸润,Eotaxin mRNA的表达水平降低,TLR4、MyD88和p-NF-κB p65蛋白的表达水平降低(P<0.05)。结论 熊果酸可调节AR大鼠的Th1/Th2平衡,减少EOS浸润,其机制可能与调节TLR4/NF-κB通路有关。Objective To observe the effect of ursolic acid on Th1/Th2 balance and eosinophils of the nasal mucosa in rats with allergic rhinitis(AR),and to explore its mechanism of action. Methods Rats were randomly divided into normal group, model group, loratadine Group(5 mg·kg^(-1)),ursolic acid high, medium and low dose groups(100,50 and 25 mg·kg^(-1)),with 10 rats in each group. By using ovalbumin to establish rat AR model and evaluate nasal symptom score, the expression levels of interleukin-2(IL-2),interferon-γ(INF-γ),interleukin-4(IL-4),interleukin-5(IL-5) and eosinophil activated chemotactic factor(Eotaxin) mRNA in the nasal IL-2 of rats were detected by RT-qPCR. The expression levels of IL-4, IL-5 and Eotaxin mRNA in the nasal mucosa of rats were determined by eosinophil granulocyte, the staining was used to observe the pathological changes of nasal mucosa. Eosinophil granulocyte eosinophil granulocyte(EOS) was counted. The expression of TLR4 NF-κB signal pathway protein was detected by Western blot.Results Compared with the normal group, the expression of IL-2 and INF-γ mRNA in the nasal mucosa of the model group was significantly decreased, and the expression of IL-4 and IL-5 mRNA was significantly increased, the expression of Eotaxin mRNA,TLR4,Myd88 and p-NF-κB p65 protein were significantly increased(P<0.05). Compared with the model group, the score of nasal symptoms in ursolic acid group was decreased, the expression levels of IL-2 and INF-γ mRNA in nasal mucosa were increased, and the expression levels of IL-4 and IL-5 mRNA were decreased, the epithelial cells of nasal mucosa grew well and had intact structure, with a little EOS infiltration. The expression levels of Eotaxin mRNA,TLR4,Myd88 and p-NF-κB p65 protein were decreased(P<0.05). Conclusion Ursolic acid can regulate Th1/Th2 balance and decrease EOS infiltration in AR rats, which may be related to the regulation of TLR4/NF-κB pathway.

关 键 词：熊果酸 变应性鼻炎 TH1/TH2细胞因子 嗜酸性粒细胞 

分 类 号：R965[医药卫生—药理学]