白桦脂酸预处理对小鼠脑缺血再灌注时氧化应激反应的影响

Effect of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion in mice

目的 评价白桦脂酸预处理对小鼠脑缺血再灌注时氧化应激反应的影响.方法 健康3月龄雄性昆明小鼠72只,体重25 ～ 35 g,采用随机数字表法分为3组（n=24）：假手术组（S组）、脑缺血再灌注组（I/R组）和白桦脂酸预处理组（BP组）.采用阻塞大脑中动脉2h恢复灌注的方法制备小鼠脑缺血再灌注损伤模型.BP组每天胃饲白桦脂酸50 mg/kg,7d后制备模型,S组和I/R组给予等容量二甲基亚砜.于再灌注22 h时行神经行为学评分,随后处死小鼠取脑,测定脑梗死体积,计算脑梗死体积百分比,检测NADPH氧化酶（Nox1、Nox2和Nox4）及其配体p22phox的mRNA的表达,测定ROS活性及梗死区细胞凋亡率.结果 与S组比较,I/R组小鼠神经行为学评分、脑梗死体积比、ROS活性和梗死区细胞凋亡率升高,Nox1、Nox2、Nox4及其配体p22phox的mRNA表达上调（P＜0.05）;与I/R组比较,BP组小鼠神经行为学评分、脑梗死体积比、ROS活性和梗死区细胞凋亡率降低,Nox1、Nox2、Nox4及其配体p22phox的mRNA表达下调（P＜0.05）.结论 白桦脂酸预处理通过抑制氧化应激反应减轻小鼠脑缺血再灌注损伤.

Objective To evaluate the effects of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion （I/R） in mice.Methods Seventy-two male Kunming mice,aged 3 months,weighing 25-35 g,were randomly divided into 3 groups （n =24 each） using a random number table：sham operation group （group S）,I/R group,and betulinic acid preconditioning group （group BP）.Cerebral I/R was induced by middle cerebral artery occlusion in mice anesthetized with 10% chloral hydrate 40 ml/kg.In group BP,betulinic acid 50 mg/kg was administered by intragastric gavage everyday for 7 days before ischemia,while the equal volume of solvent dimethyl sulfoxide was given in S and I/R groups.At 22 h of reperfusion,neurological function was assessed and scored.The mice were then sacrificed and brains were removed for determination of infarct size,expression of NADPH oxidase （Nox1,Nox2 and Nox4） and p22phox mRNA,activity of ROS and apoptosis rate in the infarcted zone.Results Compared with S group,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly increased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was up-regulated in group I/R.Compared with group I/R,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly decreased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was down-regulated in group BP.Conclusion Betulinic acid preconditioning mitigates cerebral I/R injury through inhibiting oxidative stress response in mice.