白藜芦醇对脑梗死小鼠线粒体生物合成及脑水肿的影响

Effects of resveratrol on cerebral edema and mitochondrial biogenesis in mice with cerebral infarction

目的探讨白藜芦醇对脑梗死小鼠线粒体生物合成及脑水肿的影响。方法将36只C57BL/6雄性小鼠随机分为3组,即空白对照组(C组)、大脑中动脉栓塞组(MCAO组)和白藜芦醇组(R组),每组12只。MCAO组和R组采用线栓法构建大脑中动脉栓塞模型,随后MCAO组按1 m L/100 g剂量给予生理盐水灌胃,3次/日;R组按1 m L/100 g剂量给予2%白藜芦醇生理盐水溶液灌胃,3次/日;C组不进行任何处理。手术后72 h,进行神经功能损伤评分(m NSS),评分后立即颈椎离断法处死,取10 mg缺血半暗带脑组织,QPCR法检测PGC-1α、PPARδ、NRF1、TFAM基因表达水平和mt DNA拷贝数,剩余的患侧脑组织行脑含水量测量。结果 R组和MCAO组m NSS评分显著高于C组(P<0.05);R组和MCAO组大鼠脑组织中PGC-1α、PPARδ和TFAM基因表达以及mt DNA拷贝数均显著高于C组,且R组高于MCAO组,差异有统计学意义(P<0.05);R组和MCAO组大鼠脑组织中NRF1表达水平比较,差异无统计学意义(P>0.05),但均显著高于C组(P<0.05);MCAO组和R组大鼠脑组织含水量显著高于C组,且MCAO组高于R组,差异有统计学意义(P<0.05)。结论白藜芦醇可能通过激活PGC-1α及其下游通路,促进mt DNA生物合成,改善缺血缺氧区脑组织的能量供应,从而减轻脑水肿,发挥脑保护作用。

Objective To explore the effects of resveratrol on cerebral edema and mitochondrial biogenesis in mice with cerebral infarction. Methods Thirty-six C57 BL/6 male mice were divided into three groups,including Control group（ C group）,middle cerebral artery occlusion group（ MCAO group） and resveratrol group（ R group）. MCAO group and R group were conducted with middle cerebral artery occlusion by the intraluminal filament technics. MCAO group was given physiological saline at the dose of 1 ml/100 g by intragastric administration3 times per day. R group was given 2% resveratrol at the dose of 1 ml/100 g by intragastric administration 3 times per day. Three days after operation,the neurological function was measured and then the mice were sacrificed by cervical transection. The tissue in ischemic penumbra was taken and the expressions of PGC-1α,PPARδ,NRF1 and TFAM and the mt DNA copy number were measured by QPCR. Brain water content was measured through the remained brain tissue. Results The modified neurological severity scores（ m NSS） in R group and MCAO group were significantly increased,compared with C group（ P〈0. 05）. The PGC-1α,PPARδ and TFAM gene expression and copy number of mt DNA in R group and MCAO group were significantly increased than those in C group,in which these indexes in R group were higher than those in MCAO group. The expression of NRF1 in R and MCAO group was significantly higher than that in C group（ P〈0. 05） with no significant difference of the expression of NRF1 in R group and MCAO group shown（ P〈0. 05）. The water content of brain tissue in MCAO group and R group was significantly higher than that in C group,where the water content in MCAO group was higher than that in R group. Conclusion Resveratrol could play a protective role on brain by activating PGC-1αand downstream pathways and promoting the biosynthesis of mt DNA,thereby enhancing the energy supply during ischemia and improving brain edema.