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目的探讨盐酸戊乙奎醚对大鼠三动脉阻断法急性全脑缺血-再灌流损伤的保护作用。方法144只雄性SD大鼠随机分为假手术组、缺血-再灌流组(生理盐水1 ml)、东莨菪碱组(0.01 mg/kg)和盐酸戊乙奎醚组(0.01 mg/kg),缺血前40 min分别腹腔注射相应药物,缺血时间为10 min,于再灌流24 h、3 d和7 d测定其行为学(开阔法、平衡木法、攀绳和肌力试验),再灌流2 h、12 h、24 h、3 d和7 d取材测定海马CA1区存活神经元数量(HE染色)、凋亡神经元数量(TUNEL染色)、bcl-2和bax蛋白表达(免疫组化染色),部分大鼠于再灌流4 d测定脑梗死体积(TTC法)。结果与缺血-再灌流组比较,盐酸戊乙奎醚组和东莨菪碱组海马CA1区凋亡神经元数量减少(P<0.01),bcl-2提前并延长表达(P<0.01),盐酸戊乙奎醚组bax表达下降(P<0.05或P<0.01)。同时,盐酸戊乙奎醚组和东莨菪碱组存活神经元数量增加(P<0.05),脑梗死体积缩小(P<0.05或P<0.01),行为学检测指标改善(P<0.05)。盐酸戊乙奎醚组较东莨菪碱组作用更加明显(P<0.05)。结论盐酸戊乙奎醚对脑缺血-再灌流损伤大鼠具有脑保护作用,并且优于同样剂量东莨菪碱。改变bcl-2/bax的比例可能是其机制之一。
Objective To investigate the protective effect of penehyclidine hydrochloride against acute global cerebral ischemia-reperfusion injury induced by triosarterial occlusion in rats. Methods 144 male Sprague-Dawley rats were randomly divided into sham operation group, ischemia-reperfusion group (1 ml normal saline), scopolamine group (0.01 mg / kg) and penehyclidine hydrochloride group (0.01 mg / kg) The animals were injected intraperitoneally with corresponding drugs for 40 min before ischemia. The ischemic time was 10 min. The behavior was measured at 24 h, 3 d and 7 d after reperfusion (open method, balance beam method, climbing rope and muscle strength test), reperfusion 2 The number of surviving neurons in hippocampal CA1 area (HE staining), the number of apoptotic neurons (TUNEL staining), the expression of bcl-2 and bax protein (immunohistochemical staining) were determined at 12 h, 12 h, 24 h, , Some rats in the reperfusion 4 d after cerebral infarction volume measurement (TTC method). Results Compared with ischemia-reperfusion group, the number of apoptotic neurons in hippocampal CA1 area of penehyclidine hydrochloride and scopolamine groups was decreased (P <0.01), bcl-2 was earlier and prolonged (P <0.01) The expression of bax in ketamine group decreased (P <0.05 or P <0.01). At the same time, the number of surviving neurons in penehyclidine hydrochloride and scopolamine groups increased (P <0.05), the volume of cerebral infarction decreased (P <0.05 or P <0.01), and the behavioral indexes improved (P <0.05). Penehyclidine hydrochloride group than the scopolamine group more obvious (P <0.05). Conclusion Penehyclidine hydrochloride has neuroprotective effect on cerebral ischemia - reperfusion injury in rats and is superior to the same dose of scopolamine. Changing the ratio of bcl-2 / bax may be one of its mechanisms.