摘要
目的探究罗氟普兰对噪声性耳鸣小鼠海马NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶-1(caspase-1)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的影响。方法选取24只6~8周龄的无特定病原体雄性C57BL/6J小鼠,体重18~20 g,采用随机数字表法将其分为对照组、噪声暴露组、罗氟普兰干预组、罗氟普兰耳毒性检测组,各6只。其中噪声暴露组和罗氟普兰干预组通过100 d B宽带白噪声单次暴露2 h造模,罗氟普兰干预组、罗氟普兰耳毒性检测组连续注射7 d罗氟普兰[1 mg/(kg·d)],噪声暴露组、对照组连续注射7 d等量生理盐水。实验结束后,对四组进行听性脑干反应(ABR)、耳鸣行为学检测,对四组耳蜗基底膜进行荧光染色,采用实时荧光定量和蛋白质印迹法检测对照组、噪声暴露组、罗氟普兰干预组海马的NLRP3、caspase-1、IL-1β、TNF-α的mRNA及蛋白水平。结果干预后,四组ABR反应阈与干预前比较无明显变化。噪声暴露组间歇前抑制惊跳反射抑制率(GPIAS%)低于对照组,罗氟普兰干预组GPIAS%高于噪声暴露组(P<0.05)。罗氟普兰耳毒性检测组GPIAS%与对照组比较,差异无统计学意义(P>0.05)。四组耳蜗基底膜荧光染色显示四组内外毛细胞无明显异常。噪声暴露组NLRP3、caspase-1、IL-1β、TNF-αmRNA表达量及蛋白水平均高于对照组,罗氟普兰干预组低于噪声暴露组(P<0.05)。结论100 d B宽带白噪声可成功建立无明显听力损失的耳鸣小鼠模型,罗氟普兰无明显耳毒性,噪声暴露所致耳鸣可能与海马中炎症因子的表达量相关。
Objective To investigate the effects of Roflumram on NOD-like receptor thermal protein domain associated protein 3(NLRP3),cysteine aspartic acid specific protease-1(caspase-1)interleukin-1β(L-1B)and tumor necrosis factor-α(TNF-α)in hippocampus of noise-induced tinnitus mice.Methods A total of 24 specific pathogen free male C57BL/6J mice aged six to eight weeks,weighing 18 to 20 g,were selected and divided into control group,noise exposure group,Roflupram intervention group,and Roflupram toxicity detection group with six mice each by random number table method.Among them,the noise exposure group and the Roflupram intervention group were made by single exposure of 100 dB wide-band white noise for 2 h,the Roflupram intervention group and the Roflupram toxicity detection group were injected with Roflapram[1 mg/(kg·d)]for 7 d,and the noise exposure group and the control group were injected with the same amount of normal saline for 7 d.After the experiment,auditory brainstem response(ABR)and tinnitus behavior were detected in the four groups,and the basement membrane of cochlea in the four groups was fluorescently stained.Real-time fluorescence quantification and western blot were used to detect the mRNA and protein levels of NLRP3,caspase-1,IL-1β,and TNF-αin the hippocampus of control group,noise exposure group,and Roflupram intervention group.Results After intervention,there was no significant change in ABR response threshold in the four groups compared with before intervention.The gap prepulse inhibition of acoustic startle response inhibition ratio(GPIAS%)in the noise exposure group was lower than that in the control group,and the GPIAS%in the Roflupram intervention group was higher than that in the noise exposure group(P<0.05).There was no significant difference in GPIAS%between Roflupram toxicity detection group and control group(P>0.05).Fluorescence staining of the basement membrane of cochlea in the four groups showed no obvious abnormalities in the internal and external hair cells.The mRNA and protein ex
作者
林世童
罗丽霞
胡玉琳
农丰靖
杜政徳
刘津
LIN Shitong;LUO Lixia;HU Yulin;NONG Fengjing;DU Zhengde;LIU Jin(Graduate School,Youjiang Medical University for Nationalities,Guangxi Zhuang Autonomous Region,Baise 533000,China;Department of Otolaryngology-Head and Neck Surgery,Beijing Friendship Hospital,Capital Medical University,Beijing 100000,China;Department of Otolaryngology-Head and Neck Surgery,Affiliated Hospital of Youjiang Medical University for Nationalities,Guangxi Zhuang Autonomous Region,Baise 533000,China)
出处
《中国医药导报》
CAS
2024年第10期1-5,共5页
China Medical Herald
基金
国家自然科学基金资助项目(82171132)。
关键词
耳鸣
噪声
炎症
罗氟普兰
Tinnitus
Noise
Inflammation
Roflupram
