广藿香酮对脑卒中大鼠的影响及其作用机制

Impact of Pogostone on Rats with Stroke and Its Mechanism

背景广藿香酮(POG)具有抗癌、抗炎、抗菌等多重药理作用,但目前关于其治疗脑卒中的研究报道较少。目的探讨POG对脑卒中大鼠的影响及其作用机制。方法本实验于2018年12月-2019年4月完成。选取7~8周龄SPF级雄性Sprague-Dawley大鼠36只,随机分为空白对照组(未经模型诱导,n=6)、对照组(建模后未经治疗,n=6)、低剂量组(建模24 h后给予POG 5 mg/kg,n=6)、中剂量组(建模24 h后给予POG 15 mg/kg,n=6)、高剂量组(建模24 h后给予POG 45 mg/kg,n=6)和LY294002组(建模24 h后给予0.1%~0.3%二甲亚砜溶解浓度为0.1%,n=6)。比较六组大鼠磷酸化PI3K(p-PI3K)、磷酸化AKT(p-AKT)、磷酸化内皮型一氧化氮合酶(p-eNOS)蛋白相对表达量,血管内皮生长因子(VEGF)、B细胞淋巴瘤2 (Bcl-2)、Bcl-2相关X蛋白(Bax)蛋白及mRNA相对表达量,大脑皮质和外周血中的超氧化物歧化酶(SOD)、丙二醛(MDA)和一氧化氮(NO)水平。结果 (1)高剂量组大鼠p-PI3K、p-AKT、p-eNOS蛋白相对表达量低于对照组,p-AKT和p-eNOS蛋白相对表达量高于LY294002组(P<0.05)。(2)高剂量组大鼠Bcl-2蛋白相对表达量高于对照组,Bax、VEGF蛋白相对表达量低于对照组(P<0.05);高剂量组大鼠Bcl-2、VEGF mRNA相对表达量高于对照组,Bax mRNA相对表达量低于对照组(P<0.05)。(3)高剂量组大鼠大脑皮质和外周血NO、SOD水平高于对照组,大脑皮质和外周血MDA水平低于对照组(P<0.05);高剂量组大鼠大脑皮质和外周血MDA水平高于LY294002组,大脑皮质和外周血SOD水平低于LY294002组(P<0.05)。结论 POG可通过抑制PI3K/AKT-eNOS信号通路及脂质过氧化而减轻脑卒中大鼠脑组织损伤,且无剂量依赖性。

Background Pogostone(POG)has multiple pharmacological action,such as anti-cancer,antiinflammatory and anti-bacterial effect,however,there are few reports about POG in the treatment of stroke. Objective To investigate the impact of POG on rates with stroke and its mechanism. Methods This experiment was conducted from December 2018 to April 2019. A total of 36 SPF male Sprague-Dawley rats(7 to 8 weeks old)were selected and randomly divided into blank control group(did not prepared for stroke model,n=6),control group(did not treated after preparation of stroke model,n=6),low-dose group(received POG by 5 mg/kg 24 hours after preparation of stroke model,n=6),middle-dose group(received POG by 15 mg/kg 24 hours after preparation of stroke model,n=6),high-dose group(received POG by 45 mg/kg 24 hours after preparation of stroke model,n=6)and LY294002 group(received 0.1% to 0.3% dimethyl sulfoxide that being ultimately dissolved to 0.1% 24 hours after preparation of stroke model,n=6). Comparison was conducted in the six groups,involving relative protein expression quantity of p-PI3 K,p-AKT and p-eNOS,relative protein and RNA expression quantity of VEGF,Bcl-2 and Bax,as well as SOD,MDA and NO in cerebral cortex and peripheral blood. Results(1)Relative protein expression quantity of p-PI3 K,p-AKT and p-eNOS in high-dose group was statistically significantly lower than that in control group,respectively,while relative protein expression quantity of p-AKT and p-eNOS in high-dose group was statistically significantly higher than that in LY294002 group,respectively(P<0.05).(2)Relative protein expression quantity of Bcl-2 in high-dose group was statistically significantly higher than that in control group,relative protein expression quantity of Bax and VEGF in high-dose group was statistically significantly lower than that in control group,respectively(P<0.05);relative mRNA expression quantity of Bcl-2 and VEGF in high-dose group was statistically significantly higher than that in control group,respectively,while relative mRNA expression quantity of Bax in high-dose group was statistically significantly lower than that in control group(P<0.05).(3)NO and SOD in cerebral cortex and peripheral blood in high-dose group was statistically significantly higher than that in control group,respectively,while MDA in cerebral cortex and peripheral blood in high-dose group was statistically significantly lower than that in control group,respectively(P<0.05);MDA in cerebral cortex and peripheral blood in high-dose group was statistically significantly higher than that in LY294002 group,respectively,while SOD in cerebral cortex and peripheral blood in high-dose group was statistically significantly higher than that in LY294002 group,respectively(P<0.05). Conclusion POG may reduce the damage of brain tissue through inhibiting PI3 K/AKT-eNOS signaling pathway and lipid peroxidation in rats with stroke,without dose dependence.