熊果酸通过MAPK/ERK信号通路对变应性鼻炎小鼠炎症反应的影响  

Ursolic Acid Attenuate Inflammatory Response in Allergic Rhinitis Mice Through MAPK/ERK Signaling Pathway

作　　者：房相娟[1] 关素贞 刘永刚[2] 王慧敏[3] FANG Xiangjuan;GUAN Suzhen;LIU Yonggang;WANG Huimin

机构地区：[1]南阳市中心医院药学部,河南南阳473000 [2]南阳市中心医院耳鼻咽喉头颈外科,河南南阳473000 [3]新乡医学院第一附属医院耳鼻咽喉头颈外科,河南卫辉453100

出　　处：《新中医》2023年第5期1-6,共6页New Chinese Medicine

摘　　要：目的:探讨熊果酸对变应性鼻炎小鼠模型炎症状态的影响。方法:将40只BALB/c小鼠随机分为模型组、熊果酸组和对照组,熊果酸组小鼠根据熊果酸干预浓度差异(150 mg/mL和300 mg/mL)分成2组亚组(低剂量和高剂量熊果酸组)。模型组小鼠:将100μg卵清蛋白联合2 mg Al(OH)3溶于0.1 mL浓度为0.9%氯化钠溶液中,第0、2、4、6、8、10、12、14天对小鼠进行腹腔注射,第15天开始将500μg卵清蛋白溶于10μL 0.9%氯化钠溶液中并对小鼠进行滴鼻(每个鼻孔10μL)处理,连续激发11 d,制备变应性鼻炎小鼠模型;熊果酸组:将熊果酸溶于浓度为0.9%氯化钠溶液中配置成150 mg/mL和300 mg/mL浓度,造模的同时额外进行腹腔注射熊果酸溶液每天0.3 mL;对照组:参照模型组,采用0.9%氯化钠溶液进行处理。观察小鼠过敏性症状如喷嚏、流涕、挠鼻等行为并进行评分。检测各组小鼠鼻黏膜组织中磷酸化细胞外信号调节激酶(P-ERK)、磷酸化丝裂原活化蛋白激酶(P-MAPK)、白细胞介素-17 (IL-17)和白细胞介素-33 (IL-33)的蛋白表达水平及血清炎症因子IL-17、IL-33、肿瘤坏死因子-α (TNF-α)水平。结果:模型组小鼠症状累计得分为(8.26±0.35)分,显著高于150 mg/mL熊果酸组小鼠(6.11±0.44)分和300 mg/mL熊果酸组小鼠(4.25±1.02)分,差异均有统计学意义(P<0.05);150 mg/mL熊果酸组小鼠症状得分显著高于300 mg/mL熊果酸组小鼠,差异有统计学意义(P<0.05)。4组小鼠鼻黏膜组织中P-ERK、P-MAPK、IL-17、IL-33蛋白表达水平存在显著差异(P<0.05)。与模型组相比,熊果酸组小鼠P-ERK、P-MAPK、IL-17及IL-33蛋白表达水平均显著降低(P<0.05);对比不同剂量熊果酸组发现,300 mg/mL熊果酸组P-ERK、P-MAPK、IL-17及IL-33蛋白表达水平显著低于150 mg/mL熊果酸组(P<0.05)。与模型组比较,150 mg/mL熊果酸组小鼠血清炎症因子IL-17、IL-33及TNF-α水平显著降低;但与300 mg/mL熊果酸组相比,150 mg/mL熊果酸组血清Objective:To investigate the effect of ursolic acid on inflammatory status in allergic rhinitis mice. Methods:A total of 40 BALB/c mice were enrolled and randomly divided into model group,ursolic acid group and control group. The ursolic acid group was further divided into two sub-groups(low-dose and high-dose of ursolic acid groups) according to the different concentration of ursolic acid(150 mg/mL and300 mg/mL). Model group:the 100 μg ovalbumin combined with 2 mg Al(OH)3was dissolved in 0.1 mL of0.9% sodium chloride solution and the mice were injected intraperitoneally on day 0,2,4,6,8,10,12 and 14. On day 15 to 25,500 μg ovalbumin was dissolved in 10 μL 0.9% sodium chloride solution and treated with nasal drops(10 μL/nostril) every day. Ursolic acid group:ursolic acid was dissolved in 0.9%sodium chloride solution, and the final concentration of ursolic acid was allocated to 150 mg/mL and300 mg/mL,respectively. Ursolic acid solution was injected intraperitoneally 0.3 mL based on the model group every day. Control group: all mice were treated with 0.9% sodium chloride solution according to model group. The allergic symptoms of mice such as sneezing,runny nose and scratching were observed and scored. The protein expression levels of phosphorylated extracellular signal-regulate kinase(P-ERK),phosphorylated mitogen activated protein kinase(P-MAPK),interleukin-17(IL-17),interleukin-33(IL-33)in nasal mucosa and serum. IL-17,IL-33 and tumor necrosis factor-α(TNF-α) levels in each group of mice were detected. Results:The cumulative symptom scores of mice in the model group being(8.26±0.35),which were significantly higher than those being(6.11±0.44) in the 150 mg/mL ursolic acid group and(4.25±1.02) in the 300 mg/mL ursolic acid group,and the differences were statistically significant(P<0.05);the symptom scores of mice in the 150 mg/mL ursolic acid group were significantly higher than those in the 300 mg/mL ursolic acid group,and the differences were statistically significant(P<0.05). The protein expression lev

关 键 词：变应性鼻炎 熊果酸 炎症反应 丝裂原活化蛋白激酶/细胞外信号调节激酶信号通路 白细胞介素-17 白细胞介素-33 肿瘤坏死因子-α 

分 类 号：R285.5[医药卫生—中药学]