钩藤碱对脑缺血/再灌损伤的保护作用

 目的观察钩藤碱(rhynchophylline,Rhy)对脑缺血损伤的保护作用并初步探讨其作用机制。方法采用小鼠颈总动脉不完全结扎及大鼠四动脉结扎模型观察Rhy抗脑缺血损伤的效应,测定Rhy对脑缺血大鼠脑中超氧化物歧化酶(superoxide dis—umtase,SOD)、乳酸脱氢酶(lactare dehtdrogenase,LDH)活性及丙二醛(malondialdehyde,MDA)、一氧化氮(nitric oxide,NO)含量的影响,以及在光镜下观察脑缺血/再灌后海马CA1区的影响。结果iv Rhy 10,15 mg·kg^-1均能明显提高颈总动脉不完全结扎小鼠2 h生存率,明显改善大鼠全脑缺血/再灌后海马CA1区病变,并能提高全脑缺血/再灌后脑组织SOD,LDH活性而降低MDA,NO含量,上述作用与尼莫地平(nimodipine,Nim)0.15 mg·kg^-1相似,但Rhy 5 mg·kg^-1未见明显影响。结论iv Rhv 10,15 mg·kg^-1对脑缺血/再灌损伤有保护作用。其作用机制可能与抑制NO合成,提高SOD活性,抑制脂质过氧化有关。

Protective effects of rhynchophylline on cerebral ischemia-reperfusion injury

OBJECTIVE To observe the protective effect of rhynehophlline(Rhy) on cerebral ischemia-reperfusion injury and investigate action mechanism at the first stage. METHODS The effect of Rhy on cerebral ischemia was observed by duplicating cerebral ischemia-reperfusion models including incomplete the hgation of bilateral common carotid arteries model and four-vessel occlusion model.The activities of SOD and LDH and the contents of MDA and NO from the brain of animals subjected to cerebral ischemia-reperfusion were measured. The pathological changes of hippocampal CA1 region were observed by microscope. RESULTS The 2 h survival ratio of mice medicated intravenously with Rhy (at the doses of 10 and 15 mg·kg^-1) was significantly higher than that of control group (P<0.01). Rhy 10 and 15 mg·kg^-1 ameliorated the pathological changes of hippocampal CA1 region significantly. The average activity of SOD or LDH in the groups treated with Rhy 10 and 15 mg·kg^-1 was significantly higher than that of control group (P<0.01) .The average content of MDA or NO declined significantly (P<0.01). The protective effect showed no difference among the groups treated with Rhy 10,15 mg·kg^-1 and nimodipine 0.15 mg·kg^-1 significantly. CONCLUSION Rhy 10 and 15 mg·kg^-1 facilitated the protection against cerebral ischemia-reperfusion damage. The action mechanism might be:inhibiting the production of NO, increasing the SOD activity and inhibiting lipoperoxidation.