五苓散对脑梗死小鼠脑水肿及线粒体生物合成的影响

The Influence of Wuling Powder on the Cerebral Edema and Mitochondrial Biogenesis in Mice with Cerebral Infarction

目的探讨五苓散对脑梗死小鼠脑水肿及线粒体生物合成的影响。方法将30只雄性C57BL/6小鼠随机分为对照组(S组)、大脑中动脉栓塞组(MCAO组)和五苓散组(W组),各10只。MCAO组和W组采用线栓法构建右侧大脑中动脉栓塞模型,之后MCAO组以1mL/100g生理盐水灌胃,每日3次;W组以1mL/100g五苓散灌胃,每日3次;S组仅暴露相应部位后缝合。手术后72h进行神经功能损伤评分(mNSS),之后取10mg缺血半暗带脑组织,QPCR法检测受体γ辅激活因子1α(PGC-1α)、核呼吸因子(NRF)1、NRF2、线粒体转录因子A(TFAM)基因的表达和线粒体DNA(mtDNA)拷贝数,剩余脑组织进行脑含水量测定。结果S组、W组和MCAO组mNSS评分依次升高,差异有统计学意义(P<0.05);S组、MCAO组和W组大鼠脑组织PGC-1α和TFAM基因表达及mtDNA拷贝数依次均增高,差异有统计学意义(P<0.05);MCAO组和W组大鼠脑组织NRF1和NRF2表达水平比较,差异无统计学意义(P>0.05),但均显著高于S组(P<0.05);MCAO组、W组和S组大鼠患侧脑组织含水量依次降低,差异有统计学意义(P<0.05)。结论五苓散可能通过激活PGC-α及下游通路,促进mtDNA的生物合成,增强缺血缺氧脑组织的能量供应,进而改善脑水肿程度,发挥脑保护作用。

Objective To explore the impacts of Wuling powder（WLP）on the cerebral edema and mitochondrial biogenesis in mice with cerebral infarction.Methods Thirty male C57 BL/6 mice were randomly divided into three groups equally,including shame group,middle cerebral artery occlusion（MCAO）group,and WLP group.MCAO model were established by the intraluminal filament technics in MCAO group,and WLP group.The mice were intragastrically administered with 1 mL/100 g normal saline in MCAO group and 1 mL/100 g WLP in WLP group,three times per day.The mice were sutured after exposure of the corresponding site in shame group.At 72 hours after operation,the neurological function was evaluated by modified neurological severity scores（mNSS）,and 10 mg ischemic penumbra tissue was then taken.The expression levels of peroxisome proliferator-activated receptor-γcoactivator-1α（PGC-1α）,nuclear respiratory factor 1（NRF1）,NRF2,and mitochondrial transcription factor A（TFAM）gene expression mitochondrial DNA（mtDNA）copy number were measured by QPCR.The brain water content were performed on remaining brain tissue.Results The mNSS were increased successively in shame group,WLP group,and MCAO group（P〈0.05）.The expression of PGC-1α,TFAM and the mtDNA copy number were increased successively in shame group,MCAO group,and WLP group（P〈0.05）.The expression of NRF1 and NRF2 in MCAO group and WLP group were higher than that in shame group（P〈0.05）.The brain water contents were decreased successively in MCAO group WLP group,and shame group（P〈0.05）.Conclusion WLP can activate PGC and downstream pathways,and contribute to the biosynthesis of mtDNA,thereby enhancing the energy supply of ischemic and hypoxic brain tissue,and then improve brain edema,and play aprotective role in brain.