大麻二酚对大鼠抗脑缺血的作用机制

Effects of cannabidiol on cerebral ischemia in rats and its mechanism

目的探讨大麻二酚(CBD)对大鼠脑缺血的作用机制。方法随机将50只健康SD大鼠随机分为假手术组、模型组、CBD组(10、20、40 mg/kg),每组10只,不同组别分别给予相应的干预。造模后根据各组大鼠情况来确定最佳剂量。随机将30只健康SD大鼠分为假手术组、模型组和CBD组(最佳剂量),每组10只,再次同上造模,脑缺血再灌注24 h后采用蛋白质印迹法检测大脑皮层及海马组织中磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)以及p38丝裂原活化蛋白激酶(p38MAPK)蛋白的表达。结果与假手术组相比,模型组神经功能缺损评分降低(P<0.05);与模型组相比,CBD组(20 mg/kg和40 mg/kg)神经功能缺损评分差异具有统计学意义(P<0.05),最佳剂量为40 mg/kg。与模型组相比,CBD组PI3K、Akt、p38MAPK蛋白表达减少,差异具有统计学意义(P<0.01)。结论大麻二酚对大鼠脑缺血有保护作用,其可能作用机制是通过PI3K/Akt信号通路调控p38MAPK起到抗脑缺血作用。

Objective To investigate the protective effect and mechanism of cannabidiol(CBD)on cere-bral ischemia in rats.Methods Firstly,A total of 50 healthy SD rats were randomly divided into sham operation group,model group and cannabidiol group(10,20,40mg/kg),with 10 rats in each group.The intervention was ad-ministered separately in different groups.After modeling,the optimal dose was determined according to the condi-tions of each group of rats.Then,a total of 30 healthy SD rats were randomly divided into sham operation group,model group and cannabidiol group(optimal dose),with 10 rats in each group.The model was established again as above.The expressions of PI3K,Akt and p38MAPK in cerebral cortex and hippocampus were detected by West-ern-blot after cerebral ischemia and reperfusion 24 hours later.Results Compared with the sham operation group,the neurological deficit score of the model group was significantly reduced(P<0.05);Compared with the model group,the cannabidiol group(20 mg/kg and 40 mg/kg)had statistically significant differences in neurological deficit scores(P<0.05),and the optimal dose was 40 mg/kg,while there was no statistically significant difference in the 10 mg/kg group.Compared with the model group,the expressions of PI3K,Akt and p38MAPK proteins in cannabidiol group were decreased,and the differences were statistically significant(P<0.01).Conclusion Cannabidiol has a protective effect on cerebral ischemia in rats,and its possible mechanism of anticerebral is-chemia effect may be the regulation of p38MAPK through PI3K/Akt signaling pathway.