川芎嗪对顺铂诱导药物中毒性聋大鼠NO、H_(2)O_(2)、CAT及GSH-Px的影响  

Effects of Tetramethylpyrazine on Expression of NO,H_(2)O_(2),CAT and GSH-Px in Rats with Cisplatin-Induced Ototoxicity Deafness

作　　者：石磊[1] 冷辉[1] 马贤德[2] 王爱平[1] 曲中源[1] 马梽轩[1] 舒福 金婧 SHI Lei;LENG Hui;MA Xiande;WANG Aiping;QU Zhongyuan;MA Zhixuan;SHU Fu;JIN Jing(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China;Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)

机构地区：[1]辽宁中医药大学附属医院,辽宁沈阳110032 [2]辽宁中医药大学,辽宁沈阳110847

出　　处：《辽宁中医药大学学报》2022年第12期1-4,共4页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：辽宁省科技厅自然基金指导计划项目(2019-ZD-0952);国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号);辽宁省第一批优秀中医临床人才培养项目(辽卫办发[2021]29号)。

摘　　要：目的研究川芎嗪(tetramethylpyrazin,TMP)对顺铂(cisplatin,DDP)诱导药物中毒性聋(ototoxic deafness,OD)大鼠的一氧化氮(nitric oxide,NO)、过氧化氢(hydrogen peroxide,H_(2)O_(2))、过氧化氢酶(catalase,CAT)及谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)水平的影响,探究TMP对OD的干预作用与机制。方法先将72只健康雌性SPF级Wistar大鼠随机均分为空白组(B组)与模型组(M组),对B组大鼠进行常规饲养,对M组大鼠采用腹腔注射DDP的方式诱导OD模型,运用听性脑干反应测听(auditory brainstem response audiometry,ABR)与基底膜铺片技术对模型进行评价。于模型成功复制后,再次通过随机的方式将B组与M组各自再分为2组,分别是空白对照组(BC组),空白+川芎嗪组(BC+TMP组),模型对照组(MC组),模型+川芎嗪组(MC+TMP组)。BC+TMP组与MC+TMP组大鼠经腹腔注射TMP注射液(140 mg·kg^(-1)·d^(-1)),BC组及MC组大鼠接受等量生理盐水腹腔注射,均每日1次,连续干预2周,于末次注射给药后1 h处死大鼠。使用比色法检测各组大鼠血清中NO、H_(2)O_(2)、CAT及GSH-Px水平。结果ABR检测结果显示,与B组相比,M组大鼠ABR阈值明显提高且差异具有统计学意义(P<0.05);同时,基底膜铺片显示B组大鼠耳蜗毛细胞整齐排列,分布均匀,未见明显细胞缺失;M组大鼠耳蜗毛细胞明显变形,排列不均匀,许多细胞间连接不完全,可见大量毛细胞出现溶解破坏,ABR与基底膜铺片结果提示对M组的造模成功。此外,MC+TMP组大鼠基底膜铺片显示其耳蜗毛细胞可见缺失与变形,细胞间连接不完全,但其损伤程度低于MC组,同时,4组大鼠血清中NO、H_(2)O_(2)、CAT及GSH-Px水平检测结果显示,与BC组和BC+TMP组比较,MC组大鼠血清中NO与H_(2)O_(2)水平明显升高且差异具有统计学意义(P<0.05),CAT及GSH-Px水平明显降低且差异具有统计学意义(P<0.05);与MC组比较,MC+TMP组大鼠血清中NO与H_(2)O_(2)水平明显更低且差异具有统�Objective To study the effects of tetramethylpyrazine(TMP)on expression of nitric oxide(NO),hydrogen peroxide(H_(2)O_(2)),catalase(CAT)and glutathione peroxidase(GSH-Px)in rats with cisplatin-induced ototoxicity deafness,and to explore the intervention effect and mechanism of TMP on OD.Methods First,72 healthy female SPF Wistar rats were randomly and equally divided into blank group(group B)and model group(group M).Rats in group B were routinely fed,and rats in group M were injected with DDP intraperitoneally to induce OD model.The OD model was evaluated by auditory brainstem response audiometry(ABR)and basilar membrane technique.After the model was successfully replicated,group B and group M were randomly divided into two groups:blank control group(BC group),blank+tetramethylpyrazine group(BC+TMP group),model control group(MC group),model+tetramethylpyrazine group(MC+TMP group).Rats in BC+TMP group and MC+TMP group were intraperitoneally injected with TMP injection(140 mg·kg^(-1)·d^(-1)),and rats in BC group and MC group received intraperitoneal injection of the same amount of normal saline,once a day,for continuous intervention two weeks.Rats were sacrificed 1 hour after the last injection.The serum levels of NO,H_(2)O_(2),CAT and GSH-Px were detected by colorimetric method.Results The ABR test results showed that compared with group B,the ABR threshold of rats in group M was significantly increased and there was a statistical difference(P<0.05).At the same time,the basement membrane slice showed that the cochlear hair cells of the rats in group B were neatly arranged and evenly distributed,and there was no obvious cell loss;The cochlear hair cells of the rats in the M group were obviously deformed and unevenly arranged,and many intercellular connections were incomplete,and a large number of hair cells were dissolved and destroyed.The results of ABR and basement membrane slices indicated that the modeling of group M was successful.In addition,the basement membrane slices of the rats in the MC+TMP group showed

关 键 词：川芎嗪 顺铂 药物中毒性聋 氧自由基 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]