尼莫地平对耳蜗缺血再灌注损伤的保护作用

The Protective Effects of Nimodipine on Cochlear Impairment Induced by Ischemia-Reperfusion

目的观察尼莫地平对豚鼠耳蜗缺血再灌注损伤的保护作用并探讨其作用机制。方法 42只豚鼠随机分为干预组、实验组和正常对照组,干预组和实验组各18只,用FeCl3诱导小脑前下动脉缺血后以尿激酶溶栓制备缺血再灌注模型,干预组在应用FeCl310分钟前腹腔注射尼莫地平0.5 mg/kg,实验组在相同条件下注射等量生理盐水;正常对照组6只,不造模,不注射任何药物。连续记录各组耳蜗血流量,基底膜Hoechest33342荧光染色观察细胞核形态学变化,耳蜗中轴切片免疫组织化学染色检测螺旋神经节Casepase-3的表达。三组均于实验术前检测ABR,实验组、干预组分别于再灌注后1、2、6 h再行ABR检测。结果小脑前下动脉缺血后,实验组和干预组耳蜗血流量明显下降,再灌注后又明显回升,ABR反应阈值较对照组上升,实验组较干预组上升明显,差异有统计学意义(P<0.01)。实验组、干预组均出现内毛细胞缺损,且实验组内毛细胞缺损率较对照组高,差异有统计学意义(P<0.01)。缺血再灌注后,实验组螺旋神经节Casepase-3较干预组表达增强,差异有统计学意义(P<0.01)。结论豚鼠耳蜗缺血再灌注导致内毛细胞和螺旋神经节细胞发生凋亡损伤,尼莫地平对耳蜗缺血再灌注损伤有一定保护作用。

Objective To sutdy the protective effection and the mechanism of L type Ca^2＋ channel inhibitor nimodipine on the guinea-pig cochlea after ischemical-reperfusion injury.Methods Guinea-pigs were divided into 3 groups which were experimental group,interventional group and normal control group.The guinea-pig cochlea ischemia was induced by FeCl3 and injection of uk（urokinase） to establish the model of ischemia-reperfusion.For interventional groups,nimodipine were injected infraperitoneally before establishing the model,while the experimental group were injected with the same amount of equivalent normal saline,the normal control group did not receive any injection.In the experimental group and the interventional group,ABR were detected at 1 h、2 h、6 h after reperfusion.Meanwhile the morphological changes in guinea-pigs cochlear hair cell（HC） were examined by HC nuclei stained with hoechest 33342,and casepase-3 in guinea-pig cochlear was detected by immunohistochemical staining.Results The thresholds of ABR in experimental group and interventional group were greater than that of normal control group,and ABR threshold in experimental group was greater than that of in interventional group with statistical significance（P〈0.01）.Defective（missing and injuried） inner hair cells（IHC） were observed in both the experimenal and the interventional groups.Inner hair cell damage in the experimental group was more severe than that of in the interrentional group.After ischemia-reperfusion,there were significantly higher expression casepase-3 in SGC in exeperement group and interrentional group than that in the normal control group（P〈0.01）.Conclusion Ischemical-reperfusion injury in cochlea induce IHC and spiral ganglion apoptosis.In some degree,nimodipine can protect cochlea from the injury of ischemical-reperfusion.