巴曲酶治疗大鼠耳鸣的实验研究

Experimental research of batroxobin on rats with tinnitus

目的 观察巴曲酶对耳鸣大鼠的治疗作用及其下丘神经递质的影响。方法 采用水杨酸钠腹腔注射诱导联合饮水抑制法建立大鼠耳鸣模型,随机分为模型组、卡马西平组(5 mg/kg)和巴曲酶组(1 BU/kg),另设正常组作为对照。腹腔注射给药15 d后,记录各组饮水抑制率恢复至正常的时间,检测大鼠在不同声音频率(4~28 kHz)下的听性脑干反应(auditory brainstem response,ABR)阈值,分别采用酶联免疫吸附测定和液相色谱液质谱法检测大鼠下丘递质~γ-氨基丁酸(~γ-aminobutyric acid,GABA)、5-羟色胺(5-hydroxytrptamine,5-HT)和乙酰胆碱(acetylcholine,ACh)的含量。结果 与模型组相比,巴曲酶组饮水抑制率恢复至正常的时间显著延长(P<0.01);在不同声音频率下,巴曲酶组ABR阈值较模型组显著下降(P<0.05或P<0.01);与模型组相比,巴曲酶组下丘GABA和ACh水平均显著升高(P<0.05或P<0.01),5-HT水平则显著降低(P<0.01)。结论 巴曲酶对水杨酸钠致大鼠耳鸣具有抑制作用,可能与调节中枢可塑性变化、恢复兴奋性和抑制性递质的平衡等途径有关。

Objective To evaluate the therapeutic effect of batroxobin on rats with tinnitus and investigate its effect on neurotransmitters in inferior colliculus.Methods The tinnitus model was established by intraperitoneal injection of sodium salicylate combined with ’’drinking water suppression’’.The model rats were randomly divided into model group,positive control carbamazepine(5 mg/kg) and batroxobin(1 BU/kg) groups.Normal rats were arranged as the control group.After 15 days of intraperitoneal injection,the recovery time of drinking water suppression in each group was documented.The threshold value of auditory brainstem response(ABR) at different sound frequencies(4~28 kHz) in each rat was measured.The levels of γ-aminobutyric acid(GABA),5-hydroxytrptamine(5-HT) and acetylcholine(ACh) in inferior colliculus in rats were detected by enzyme-linked immunosorbent assay(ELISA) and liquid chromatography/mass spectrometry(LC/MS),respectively.Results Compared with the model group,the recovery time of drinking water suppression in batroxobin group was significantly longer(P<0.01).Compared with the model group,the threshold value of ABR at different sound frequencies in batroxobin group were significantly reduced(P<0.05 or P<0.01).Compared with the model group,the GABA and ACh levels in inferior colliculus in batroxobin group were markedly increased(P<0.05 or P<0.01),while the 5-HT level was markedly decreased(P<0.01).Conclusion Batroxobin could relieve tinnitus symptoms induced by sodium salicylate in rats,which may be related to the regulation of central neural plasticity and recovery of the balance of excitatory/inhibitory neurotransmitters.