香荆芥酚对药物性耳聋模型大鼠的治疗作用及NOX3/STAT1信号通路的影响  

Therapeutic Effect of Carvacrol in Rats with Drug-induced Deafness and its Influence on NOX3/STAT1 Signaling Pathway

作　　者：臧雯 周鲲鹏 于颖 Zang Wen;Zhou Kunpeng;Yu Ying(Department of Otolaryngology,Shijiazhuang People's Hospital,Shijiazhuang 050011,China)

机构地区：[1]石家庄市人民医院耳鼻咽喉科,石家庄050011

出　　处：《中国药师》2021年第2期223-226,231,共5页China Pharmacist

基　　金：石家庄市科学技术研究与发展指导计划项目(编号:171201233)。

摘　　要：目的:探讨香荆芥酚对药物性耳聋模型大鼠的治疗作用及NADPH氧化酶3(NOX3)/转录活化因子1(STAT1)信号通路的影响。方法:72只Wistar大鼠随机分成4组:正常对照组、模型组、香荆芥酚低、高剂量组(1.25,2.5 mg·kg^(-1)),每组18只。除正常对照组外,其余各组建立顺铂耳聋模型,建模成功后,香荆芥酚低、高剂量组用相应剂量药物灌胃治疗,正常对照组和模型组给予等体积0.9%氯化钠溶液,连续给药4周。给药结束后,测定大鼠听性脑干反应(ABR)阈值,电镜观察大鼠耳蜗组织改变,实时荧光定量PCR(qRT-PCR)法及蛋白免疫印迹法(WB)法测定耳蜗组织NOX3、STAT1 mRNA及蛋白表达水平。结果:模型组ABR阈值水平、耳蜗组织NOX3、STAT1 mRNA和蛋白水平显著高于正常对照组(P<0.05);香荆芥酚低、高剂量组ABR阈值水平、耳蜗组织NOX3、STAT1 mRNA和蛋白水平显著低于模型组(P<0.05),且香荆芥酚高剂量组ABR阈值水平、耳蜗组织NOX3、STAT1 mRNA和蛋白水平显著低于香荆芥酚低剂量组(P<0.05)。正常对照组耳蜗毛细胞结构正常;模型组耳蜗内、外毛细胞排列紊乱,与螺旋神经节细胞周围突结合出现裂隙;香荆芥酚高剂量组耳蜗内、外毛细胞排列趋于正常,与螺旋神经节细胞周围突结合处仍然有裂隙,但裂隙较小;香荆芥酚低剂量组仍然可见耳蜗内、外毛细胞排列紊乱。结论:香荆芥酚可降低药物性(顺铂)耳毒性,其机制可能与香荆芥酚抑制药物性耳聋模型大鼠耳蜗组织中NOX3、STAT1 mRNA和蛋白的表达进而抑制NOX3/STAT1炎症通路的激活有关。Objective: To investigate the therapeutic effect of carvacrol in rats with drug-induced deafness and its influence on NADPH oxidase 3(NOX3)/signal transducer and activator of transcription(STAT1) signaling pathway. Methods: Totally 72 Wistar rats were randomly divided into four groups: normal control group,model group,carvacrol low and high dose groups(1.25,2.5 mg·kg^(-1)) with 18 ones in each group. Except the normal control group,the other groups established cisplatin deafness model. After the successful modeling,the rats in carvacrol low and high dose groups were treated with corresponding dose of drug by gavage,and the rats in the normal control group and the model group were given equal volume of 0.9% sodium chloride solution for 4 weeks. At the end of administration,the ABR threshold of rats was measured,and the changes of cochlear tissues were observed by electron microscopy,and the expression levels of NOX3 and STAT1 mRNA and protein in cochlear tissues were determined by real-time fluorescence quantitative PCR(qRT-PCR) and Western blot(WB). Results: The ABR threshold level,NOX3,STAT1 mRNA and protein levels of cochlea tissue in the model group were higher than those in the normal control group(P < 0.05). The ABR threshold level,NOX3,STAT1 mRNA and protein levels of cochlea tissue in carvacrol low and high dose groups were lower than those in the model group(P<0.05),and the ABR threshold level,NOX3,STAT1 mRNA and protein levels in carvacrol high dose group were lower than those in carvacrol low dose group(P<0.05). The cochlear hair cells of the normal control group were normal;the inner and outer hair cells of the model group were disorderly arranged,and there were cracks in conjunction with the peripheral ganglion of spiral ganglion cells;in carvacrol high dose group,the arrangement of inner and outer hair cells tended to be normal,and there were still cracks in conjunction with the peripheral processes of spiral ganglion cells,while the cracks were small;carvacrol low dose group still showed disordered

关 键 词：香荆芥酚 药物性耳聋 NADPH氧化酶3/转录活化因子1信号通路 

分 类 号：R965.1[医药卫生—药理学]