白术内酯Ⅰ调控Janus激酶2/信号转导和转录激活因子3通路对分泌性中耳炎大鼠听功能及炎症反应的影响

Influences of atractylenolideⅠon auditory function and inflammatory response in rats with secretory otitis media by regulating Janus kinase 2/signal transducer and activator of transcription 3 pathway

目的探究白术内酯Ⅰ调控Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)通路对分泌性中耳炎(SOM)大鼠听功能及炎症反应的影响。方法用卵清蛋白和氢氧化铝致敏构建SOM模型大鼠,并随机分为模型组、联合组和低、高剂量实验组,每组12只;另选12只正常SD大鼠做对照组。低、高剂量实验组分别灌胃给予120和240 mg·kg^(-1)白术内酯Ⅰ,联合组灌胃给予240 mg·kg^(-1)白术内酯Ⅰ+21 mg·kg^(-1)RO8191;对照组和模型组均灌胃给予等量0.9%NaCl。5组大鼠每天给药1次,连续给药14 d。用听觉脑干诱发电位(ABR)仪检测大鼠听功能(ABR反应阈值),用蛋白质印迹法检测大鼠中耳黏膜组织JAK2/STAT3通路相关蛋白的表达情况。结果低、高剂量实验组和联合组、模型组、对照组的ABR反应阈值分别为(47.26±5.91)、(26.89±3.75)、(63.37±9.87)、(68.71±10.32)和(24.62±3.53)dB SPL,p-JAK2/JAK2分别为0.48±0.09、0.16±0.05、0.73±0.12、0.79±0.11和0.12±0.03,p-STAT3/STAT3分别为0.53±0.10、0.20±0.06、0.79±0.15、0.84±0.13和0.15±0.04。低、高剂量实验组和对照组的上述指标与模型组和联合组相比,差异均有统计学意义(均P<0.05)。结论白术内酯Ⅰ可通过下调JAK2/STAT3通路抑制炎症,减轻SOM大鼠中耳炎症状及中耳黏膜病理损伤,修复其听功能。

Objective To explore the influences of atractylenolideⅠon auditory function and inflammatory response in rats with secretory otitis media(SOM)by regulating Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods The SOM model rats were sensitized with ovalbumin and aluminum hydroxide.They were randomly divided into model,combined and experimental-L,-H groups,with 12 rats in each group.Another 12 normal SD rats were selected as the control group.The experimental-L,-H groups were given 120 and 240 mg·kg^(-1)atractylenolide I by gavage;the combined group was given 240 mg·kg^(-1)atractylenolide I and 21 mg·kg^(-1)RO8191 by gavage;the control and model groups were given 0.9%NaCl by ga vage.Five groups were administered once a day for 14 days.Auditory brainstem response(ABR)apparatus was used to detect rat auditory function(ABR response threshold).Western blotting was used to detect the expression of JAK2/STAT3 pathway-related proteins in the middle ear mucosa of rats.Results The ABR reaction thresholds of experimental-L,experimental-H,combined,model and control groups were(47.26±5.91),(26.89±3.75),(63.37±9.87),(68.71±10.32)and(24.62±3.53)dB SPL;p-JAK2/JAK2 were 0.48±0.09,0.16±0.05,0.73±0.12,0.79±0.11 and 0.12±0.03;p-STAT3/STAT3 were 0.53±0.10,0.20±0.06,0.79±0.15,0.84±0.13 and 0.15±0.04,respectively.The above indexes of the experimental-L,-H groups and control group were compared with those of model and combined groups,and the differences were statistically significant(all P<0.05).Conclusion AtractylenolideⅠcan inhibit inflammation by down-regulating JAK2/STAT3 pathway,relieve the symptoms of otitis media and pathological damage of middle ear mucosa in SOM rats,and restore their auditory function.