左旋四氢巴马汀在脑缺血再灌注损伤中作用的实验研究

Experimental Study of Protective Effect of L-Tetrahydropalmatine on Cerebral Ischemia/Reperfusion Injury

目的 :探讨左旋四氢巴马汀 (L tetrahydropalmatine,L THP)对脑缺血再灌注损伤的保护作用。方法 :采用小鼠和大鼠脑缺血模型 ,并术前 30min分别腹腔内注射生理盐水 (10ml/kg)、L THP(5 ,10 ,2 0mg/kg)和尼莫地平(0 0 4mg/kg) ,观察小鼠存活时间、大鼠神经功能缺损评分、脑梗死范围、超氧化物歧化酶 (SOD)活性、丙二醛 (MDA)和一氧化氮 (NO)含量的改变。结果 :与生理盐水组比较 ,L THP组可显著延长脑缺血小鼠的存活时间 ,改善脑缺血2h再灌注不同时间大鼠的神经功能缺损 ,缩小脑梗死范围 ,增加SOD活性、降低MDA和NO含量 (P <0 0 5 ) ;10、2 0mg/kgL THP作用与尼莫地平差异无显著性 (P >0 0 5 )。结论 :L THP可通过抗自由基与减轻NO介导的神经毒性机制发挥对脑缺血再灌注损伤的神经保护作用。

Objective: To evaluate the neuroprotective effects of L-Tetrahydropahmatine (L-THP) on cerebral ischemia/reperfusion injury. Methods: The mouse model of cerebral ischemia was established by bilateral carotid artery occlusion and rat model of middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for different time were established using thread embolism. Group Ⅰ was treated with 0.9 % saline (10 ml/kg), group Ⅱ received L-THP (5, 10, 20 mg/kg) and group Ⅲ received Nimodipine (0.04 mg/kg) intraperitoneal injection 30 min prior to vascular occlusion. At the end of experiments, the survival time, neurologic deficits, infarct area, the activity of superoxide disroutase (SOD), and the contents of malondialdehyde (MDA) and nitric oxide (N0) were measured. Results:As compared with group Ⅰ, L-THP could significantly prolong the survival time of the mice, improve the neurologic deficits of the rats subject to cerebral ischemia for 2 h and reperfusion for different time, shrink the infarct area, increase the SOD activity and decrease the MDA and NO contents, respectively ( P <0.01). No difference was found between group Ⅱ (10, 20 mg/kg L-THP) and group Ⅲ respectively ( P >0.05). Conclusion:L-THP provides neuroprotection by antagonizing free radicals and alleviating NO-induced neurotoxic effect on cerebral ischemia/reperfusion injury.