川芎嗪对顺铂耳毒性大鼠耳蜗组织Nrf2/NQO1信号通路相关蛋白表达影响  

Effect of Ligustrazine on the Expression of Nrf2/NQO1 Signal Pathway Related Proteins in the Cochlea of Cisplatin Ototoxic Rats

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

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

出　　处：《辽宁中医药大学学报》2023年第2期28-32,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：辽宁省自然基金项目(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〔2022〕29号)。

摘　　要：目的探讨川芎嗪(即四甲基吡嗪,tetramethylpyrazine,TMP)对顺铂耳毒性大鼠的作用机制,以及血清中谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)含量变化、耳蜗组织中肌腱膜纤维肉瘤癌基因(musculoaponeurotic fibrosarcoma,Maf)、血红素氧合酶1(HO-1)和还原型辅酶/醌氧化还原酶(NQO1)蛋白表达对其的影响。方法采用腹腔注射顺铂(4 mg/kg)诱导顺铂耳毒性大鼠模型。将大鼠随机分为空白对照组、空白+TMP组、模型对照组(M组)、模型+TMP组。通过比较大鼠听性脑干反应(auditory brainstem response,ABR)听力阈值的变化、基底膜铺片技术观察内耳毛细胞纤毛形态变化(硝酸银染色),评估TMP对顺铂耳毒性大鼠耳蜗毛细胞结构的影响。比色法测定大鼠血清中GSH-Px含量变化。Western blot检测法检测各组大鼠耳蜗组织中Maf、HO-1和NQO1的表达变化。结果与空白组相比,模型组大鼠血清中抗氧化酶GSH-Px活性显著下降(P<0.05),耳蜗组织中Maf、NQO1和HO-1基因表达均呈上升趋势;与模型对照组比较,模型+TMP组能够显著提高药物性耳聋大鼠血清中抗氧化酶GSH-Px(P<0.05)活性,增加耳蜗组织中Maf,NQO1和HO-1的蛋白的相对表达(P<0.05)。结论TMP对药物性耳聋大鼠病理损伤具有恢复作用,其机制可能与血清中GSH-Px含量变化和Nrf2/NQO1信号通路相关蛋白的表达有关。Objective To investigate the mechanism of tetramethylpyrazine(TMP)on cisplatin ototoxicity in rats,and the changes of glutathione peroxidase(GSH-Px)in serum,musculo aponeurotic fibrosarcoma oncogene(Maf)in cochlea,effects of heme oxygenase-1(HO-1)and reduced coenzyme/quinone oxidoreductase(NQO1)protein expression on them.Methods The rat model of cisplatin ototoxicity was induced by intraperitoneal injection of cisplatin(4 mg/kg).The rats were randomly divided into blank control group,blank+TMP group,model control group and model+TMP group.The effect of TMP on the structure of cochlear hair cells in cisplatin ototoxic rats was evaluated by comparing the changes of auditory brainstem response(ABR)hearing threshold and the changes of cilia morphology of inner ear hair cells(silver nitrate staining).The content of GSH-Px in rat serum was measured by colorimetry.The expressions of Maf,HO-1 and NQO1 in the cochlea of rats in each group were detected by Western blot.Results Compared with the blank group,the activity of antioxidant enzyme GSH-Px in serum of model group decreased significantly(P<0.01),and the expression of Maf,NQO1 and HO-1 genes in cochlea increased;Compared with model control group,model+TMP group could significantly increase the activity of serum antioxidant enzyme GSH-Px(P<0.01)and the relative expression of Maf,NQO1 and HO-1 proteins in cochlea(P<0.05).Conclusion TMP can restore the pathological injury of drug-induced deafness rats,and its mechanism may be related to the change of GSH-Px content in serum and the expression of Nrf2/NQO1 signal pathway related proteins.

关 键 词：川芎嗪 氧化应激 药物性耳聋 Nrf2/NQO1 

分 类 号：R285.5[医药卫生—中药学]