脑源性神经营养因子减轻神经性耳聋模型大鼠氧化应激反应的机制探究

Study on the mechanism of brain-derived neurotrophic factoralleviating oxidative stress response in rats with sensorineural hearing loss

目的探究脑源性神经营养因子(BDNF)对神经性耳聋(SNHL)大鼠的保护作用机制。方法SD大鼠分为空白组(6只)和实验组(24只),其中空白组正常饲养,未行任何处理;实验组进行SNHL大鼠造模并筛选符合要求的大鼠(18只)进一步分为BDNF组和对照组,两组分别经大鼠圆窗渗透给予BDNF工作液与生理平衡液。2周后行听信脑干反应测定,并处死大鼠取耳蜗行苏木素-伊红(HE)染色和免疫荧光染色,检测超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的活力水平。结果HE染色和免疫荧光染色显示,空白组大鼠耳蜗内螺旋神经节细胞病理形态无明显改变,对照组大鼠耳蜗内螺旋神经节细胞结构明显受损,免疫荧光染色可见大量坏死的细胞碎片,BDNF组螺旋神经节细胞与对照组比较损伤明显减轻。给药2周后,与空白组比较,对照组和BDNF组大鼠听觉脑干诱发电位(ABR)阈值差值明显增大(P<0.01或P<0.05);且与对照组比较,BDNF组ABR阈值差值明显减小(P<0.05)。与空白组比较,对照组和BDNF组CAT、SOD、GSH-Px的表达水平明显降低,MDA表达水平明显升高(P<0.05);与对照组比较,BDNF组CAT、SOD、GSH-Px的表达水平明显升高,MDA表达水平明显降低(P<0.05)。结论BDNF可减轻SNHL大鼠的氧化应激损伤反应,对受损耳蜗具有一定的保护作用。

Objective To explore the mechanism of the protective effect of brain-derived neurotrophic factor(BDNF)in sensorineural hearing loss(SNHL)rats.Methods SD rats were divided into the blank group(6 rats)and the experimental group(24 rats).The blank group was fed normally without any treatment.In the experimental group,a rat model of SNHL was established,and 18 qualified rats were selected and divided into the BDNF group and the control group.Rats in the BDNF group and the control group were administered with BDNF working solution and physiological balance solution through round window separately.After two weeks,the auditory brainstem response(ABR)was measured.The rats were sacrificed,and the cochlea was taken for hematoxylin-eosin(HE)staining and immunofluorescence staining.Then the activity levels of superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA),glutathione peroxidase(GSH-Px)were detected.Results HE and immunofluorescence staining showed that the pathological morphology of spiral ganglion cells in the blank group was not significantly changed,while the structure of spiralganglion cells in the control group was significantlydamaged.A large number of necrotic cell fragments were observed by immunofluorescence staining.Compared with the control group,the damage of spiral ganglion cells in the BDNF group was significantly reduced.Two weeks after administration,compared with the blank group,the changes of ABR thresholds difference in the control group and the BDNF group were significantly increased(P<0.01 or P<0.05);additionally,compared with the control group,the changes of ABR thresholds differencein the BDNF group was significantly decreased(P<0.05).Compared with the blank group,the expression levels of CAT,SOD and GSH-Px in the control group and the BDNF group were significantly increased,and the expression levels of MDA was significantly increased(P<0.05);additionally,compared with the control group,the expression levels of CAT,SOD and GSH-Px in the BDNF group were significantly increased,and the expression level of MDA was decreased(P<0.05).Conclusion BDNF can alleviate the oxidative stress injury response of SNHL rats,and has a certain protective effect on the damaged cochlea.