VPA对颅脑损伤大鼠脑组织及行为能力的影响

Effect of VPA on brain tissue and behavioral ability of brain injury rat

[目的]探讨丙戊酸钠(valproic acid,VPA)对创伤性颅脑损伤大鼠脑组织及行为能力的影响。[方法]将100只成年雄性SD大鼠随机分为假手术组、创伤性颅脑损伤组、VPA低剂量组(30 mg)、VPA中剂量组(150 mg)、VPA高剂量组(300 mg),每组20只。比较各组大鼠改良神经功能缺损评分(modified neurological severity scores,mNSS)、脑组织含水量、垂直以及水平活动得分、脑组织中基质金属蛋白酶(MMP)-9、水通道蛋白(AQP)-4、雌激素受体(ERα)、Wnt3a和β-Catenin表达量。[结果]创伤性颅脑损伤组和VPA低、中、高剂量组大鼠mNSS评分、脑组织含水量、AQP4、MMP-9水平均高于假手术组(P<0.05),且VPA低、中、高剂量组均呈下降趋势,均存在显著差异(P<0.05)。创伤性颅脑损伤组和VPA低、中、高剂量组大鼠各时间点的水平和垂直运动水平均明显下降(P<0.05);且VPA低、中、高剂量组大鼠呈逐渐改善趋势,均存在显著差异(P<0.05)。Western Blot结果显示不同剂量VPA对大鼠脑组织ERα、Wnt3a和β-Catenin表达存在显著影响(P<0.05),且以VPA高剂量组ERα、Wnt3a和β-Catenin升高最显著(P<0.05)。[结论]VPA能够通过激活ERα-Wnt/β-Catenin信号通路和降低脑损伤模型大鼠脑组织AQP4、MMP-9蛋白表达水平改善大鼠脑水肿症状,发挥脑保护作用,且高剂量作用更显著。

[Objective]To investigate the effect of valproic acid(VPA)on brain tissue and behavior in rats with traumatic brain injury(TBI).[Method]100 adult male SD rats were randomly divided into sham operation group,TBI group,VPA low dose group(30 mg),VPA medium dose group(150 mg),VPA high dose group(300 mg),20 mice per group.The modified neurological severity scores(mNSS),brain tissue water content,vertical and horizontal activity scores,expression of matrix metalloproteinase(MMP)-9,aquaporin(AQP)-4,estrogen receptor(ERα),Wnt3 a andβ-Catenin in brain tissue were compared.[Result]The mNSS score,brain tissue water content,AQP4 and MMP-9 levels of rats in TBI and low,medium and high VPA groups were higher than those in sham operation group(P<0.05),and VPA low,medium and high dose groups showed a downward trend,with significant differences(P<0.05).The horizontal and vertical movement levels of rats in TBI group and VPA low,medium and high dose groups were significantly decreased(P<0.05).VPA low,medium and high dose groupss showed a trend of gradual improvement,there were significant differences(P<0.05).Western Blot results showed that different doses of VPA had a significant effect on the expression of ERα,Wnt3 a andβ-Catenin in rat brain tissue(P<0.05),and the highest increase in ERα,Wnt3 a andβ-Catenin in the high-dose VPA group significantly(P<0.05).[Conclusion]VPA can improve the symptoms of brain edema in rats by activating the ERα-Wnt/β-Catenin signaling pathway and reducing the expression of AQP4 and MMP-9 protein in the brain tissues of rats with brain injury,and the high-dose effect is more significant.