阿魏酸钠治疗梅尼埃病模型小鼠的效果及机制研究  

Effect and mechanism of sodium ferulate on Ménière disease model mice

作　　者：崔彦儒[1] 郑艳秋[1] 高伟[1] CUI Yanru;ZHENG Yanqiu;GAO Wei(Department of Otolaryngology Head and Neck Surgery,Inner Mongolia Medical University Affiliated Hospital,Hohhot 010059,China)

机构地区：[1]内蒙古医科大学附属医院耳鼻咽喉头颈外科,010059

出　　处：《天津医药》2024年第6期584-588,共5页Tianjin Medical Journal

基　　金：内蒙古自治区自然科学基金项目(2019LH08009)。

摘　　要：目的探讨阿魏酸钠治疗梅尼埃病(MD)模型小鼠的效果及机制。方法BALB/c小鼠采用后颅窝硬膜外入路内淋巴囊阻塞术联合腹腔注射醛固酮的方法构建MD模型,将造膜成功的60只小鼠随机分为模型组,阿魏酸钠低、中、高剂量组,地塞米松组,每组12只。另取12只BALB/c小鼠作为假手术组。分组鼓室给药后以听觉诱发脑干反应(ABR)检测各组小鼠听力水平。HE染色及磁共振成像(MRI)观测各组小鼠耳蜗形态及其膜迷路积水情况;酶联免疫吸附试验检测各组小鼠血清脂蛋白(a)[Lp(a)]及促炎因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平;免疫组织化学染色及Western blot法检测各组小鼠Lp(a)表达。结果与假手术组比较,模型组小鼠ABR阈值、膜迷路积水评分、中阶面积占比、血清Lp(a)、IL-6与TNF-α水平、耳蜗组织Lp(a)阳性表达的IOD值与Lp(a)蛋白表达增加(P<0.05);与模型组比较,阿魏酸钠低、中、高剂量组及地塞米松组小鼠ABR阈值、膜迷路积水评分、中阶面积占比、血清Lp(a)、IL-6与TNF-α水平、耳蜗组织Lp(a)阳性表达的IOD值与Lp(a)蛋白表达降低(P<0.05),且高剂量阿魏酸钠效果更明显。结论阿魏酸钠可下调Lp(a)蛋白表达,减少促炎因子产生,抑制炎症反应,进而减轻MD小鼠膜迷路积水症状,并改善其听觉功能。Objective To investigate the effect and mechanism of sodium ferulate in the treatment of Ménière disease(MD)model mice.Methods BALB/c mice were selected,and an MD model was constructed using posterior fossa epidural approach combined with intraperitoneal injection of aldosterone.Sixty model mice were randomly grouped into the model group,the low dose sodium ferulate group,the medium dose sodium ferulate group,the high dose sodium ferulate group and the dexamethasone group,with 12 mice in each group.Another 12 BALB/c mice were selected as the sham operation group.After grouping and tympanic administration,auditory evoked brainstem response(ABR)was applied to detect the hearing level of mice in each group.HE staining and magnetic resonance imaging(MRI)were applied to observe the morphology of cochlea and membranous labyrinth hydrops of mice in each group.Enzyme-linked immunosorbent assay was applied to detect serum levels of lipoprotein a[Lp(a)],pro-inflammatory factor interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in each group.Immunohistochemical staining and Western blot assay were applied to detect the expression of Lp(a)in each group.Results Compared with the sham operation group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,serum levels of Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly increased in the model group(P<0.05).Compared with the model group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,levels of serum Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly decreased in the low,medium and high dose sodium ferulate groups and the dexamethasone group(P<0.05),and the effect of high dose sodium ferulate was more obvious.Conclusion Sodium ferulate can down regulate the expression of Lp(a)protein,reduce the production of

关 键 词：梅尼埃病 脂蛋白(a) 阿魏酸钠 鼓室给药 

分 类 号：R764.3[医药卫生—耳鼻咽喉科]