研究白果内酯对大鼠脑缺血/再灌注损伤的保护作用

Protective Effects of Bilobalide on Cerebral Ischemia-Reperfusion Injury in Rats

目的:观察白果内酯对大鼠脑缺血/再灌注损伤的保护作用。方法:采用MCAO方法制备大鼠脑缺血/再灌注损伤模型,健康雄性SD大鼠,体重250~280 g,随机分为假手术组、模型组、MCAO+白果内酯2.5 mg·kg^(-1)组、MCAO+白果内酯5 mg·kg^(-1)组、MCAO+白果内酯10 mg·kg^(-1)组和MCAO+3 mg·kg^(-1)依达拉奉组。实验动物于MCAO手术后10 min舌下静脉给不同浓度药物1次,假手术组及模型组于同时间点给予同体积的生理盐水+DMSO,缺血2 h,再灌注24 h后,对大鼠行神经功能行为评分;取出前脑做TTC染色,测定脑梗死面积以及脑水肿体积;用western blot法测定脑组织中IL-6、IL-1β以及NF-κB的含量。结果:(1)与模型组相比,各剂量白果内酯治疗后大鼠神经功能评分均降低,差异有统计学意义(P<0.01);(2)各剂量白果内酯治疗后脑梗死体积均缩小;(3)模型组大鼠脑水肿体积升高(P<0.001),各剂量白果内酯组脑水肿体积降低,各剂量组差异有统计学意义(P<0.001);(4)模型组大鼠脑组织炎性细胞因子IL-6(P<0.001)、IL-1β(P<0.01)、NF-κB(P<0.05)的含量升高;各剂量白果内酯组脑组织IL-6(高剂量P<0.01,中剂量P<0.01,低剂量P<0.05)、IL-1β(高剂量P<0.001,中剂量P<0.001,低剂量P<0.001)、NF-κB(高剂量P<0.01、中剂量P<0.01、低剂量P<0.01)含量均降低。结论:白果内酯可能通过脑梗死面积、脑水肿体积,减少脑组织中IL-6、NF-κB以及IL-1β的含量,从而减少脑组织损伤,保护大鼠脑神经功能。

Objective： To observe the protective effect of bilobalide on cerebral ischemia-reperfusion injury in rats. Methods ： Focal cerebral ischemia-reperfusion model in rats was made by transient occlusion of middle cerebral artery. Healthy male SD rats, 250 - 280 g, were randomly divided into control group, model group, MCAO ＋ bilobalide 2.5 mg ·kg^-1 group, MCAO ＋ 5 mg·kg^-1 group, MCAO ＋ 10 mg·kg^-1 group and MCAO ＋ 3 mg·kg^-1edaravone group. The experimental animals were treated with different doses of bilobalide using sublingual vein injection 10 min after MCAO surgery. The sham operation group and model group were given the same volume of normal saline ＋ DMSO at the same time. 2 h of ischemia and 24 h of reperfusion after, the neurological function was scored. The cerebral tissue was stained by using the TTC method; the cerebral edema and the volume of infarction were investigated. The left brain tissue was used to detect the levels of IL-6,IL-1β,NF-κB in them by western blot. Results： （1） Compared with the model group, the rats nerve function scores were lower after treatment of different dose of bilobalid; the difference was statistically significant （ P 〈 0.01 ）. （2） Infarct volumes were reduced in the groups of bilobalide treatment. （3） The cerebral edema in model group increased （P 〈 0. 001 ） ,while in different dose of bilobalide treantment group reduced; difference was statis- tically significant （ P 〈 0. 001 ）. （4） In model group, the levels of proinflammatory cytokines IL-6 （ P 〈 0. 001 ）, IL-1β （ P 〈 0.01 ）, NF-KB（ P 〈 0.05 ） increased in serum ; in the different doses of bilobalide group, the levels of IL-6 （ high-dose P 〈 0. 01, middle-dose P 〈 0.01, low-dose P 〈 0. 05 ）, IL-1β （ high-dose P 〈0. 001, middle-dose P 〈 0. 001, low- dose P 〈0. 001 ）, NF-κB （ high-dose P 〈 0. 01, middle-dose P 〈 0. 01,low-dose P 〈 0. 01 ） in serum were reduced. Con- dusion： Bilobalide protects the function of brain nerve in rats possibly by reducing brain injury through decreasing the volume of cerebral infarction area and cerebral edema, reducing the content of IL-6 ,IL-113,NF-KB in brain tissue.