吴茱萸次碱对脑缺血再灌注小鼠的保护作用及作用机制研究

Effects of Rutaecarpine on Cerebral Ischemia-Reperfusion in Mice and its Mechanisms

目的:观察吴茱萸次碱(Rut)对脑缺血再灌注(I/R)损伤小鼠的学习记忆能力的保护作用及作用机制。方法:采用改进的Himori法暂时性阻断两侧颈总动脉制备小鼠脑I/R损伤模型,采用跳台实验,观察腹腔注射吴茱萸次碱(84,252,504μg.kg-1)对脑I/R损伤小鼠的学习记忆能力的保护作用,并于缺血再灌注后48 h测定小鼠脑组织中一氧化氮(NO)的含量、一氧化氮合酶(NOS)和诱导性一氧化氮合酶(iNOS)的活性。结果:脑缺血再灌注后,小鼠学习记忆能力降低,脑组织中NO的含量,NOS和iNOS的活力升高。腹腔注射吴茱萸次碱可不同程度的改善脑I/R损伤造成的学习记忆能力障碍;吴茱萸次碱可降低NO的含量,NOS和iNOS的活力;与模型组比较,吴茱萸次碱(504μg.kg-1)可显著改善小鼠的学习记忆功能障碍,降低NO的含量,NOS和iNOS的活力(P<0.01)。结论:吴茱萸次碱对脑缺血再灌注(I/R)损伤小鼠的学习记忆能力具有保护作用,其机制可能与降低NO的含量,影响NOS和iNOS的活力有关。

Objective： To observe the protective function of rutaecarpine （Rut） on learning and memory impairment induced by cerebral ischemia-reperfusion in mice and its possible mechanisms. Method： The bilateral common carotid artery occlusion for 5 min were conducted in mice, the mice in Rut-treated groups were administered with Rut（84, 252, 504 μg·kg-1, respectively）ip before 30 min of the operation. The other groups were administered with DMSO（0.02 mL·10 g-1）.The abilities of learning and memory were examined by step-down test.The content of nitric oxide（NO） and the activities of nitric oxide syhthase（NOS） and inducible nitric oxide synthase（iNOS） were measured by UV spectrophotometry scenery. Result： Focal cerebral ischemia-reperfusion injury could induce the disorder of learning and memoryin step-down test, the latency of Rut-treated groups was significantly extended（P〈0.01）, rutaecarpine could decrease the content of NO significantly and the activities of NOS and iNOS in mice brain. Conclusion： Rut could significantly improve the impairment of learning and memory and might decrease cerebral ischemia reperfusion injury by decreasing the activities of NOS and iNOS of mice brain.