摘要
目的观察格列本脲对脑外伤大鼠脑水肿的影响,并初步探究其治疗创伤性脑损伤的相关分子机制。方法以Feeney′s自由落体撞击法构建外伤性脑损伤模型,将造模大鼠分为模型组、格列本脲低剂量组(腹腔注射5μg·kg^(-1)格列本脲)和格列本脲高剂量组(腹腔注射10μg·kg^(-1)格列本脲),每组32只;另选32只作为假手术组(仅开骨窗,不进行撞击处理,其余操作同模型组),模型组与假手术组均腹腔注射等量二甲基亚砜(DMSO),每日1次,连续给药5 d;分别于术后观察各组大鼠基本情况;分别于术后6 h、1 d、3 d、5 d时,各取8只大鼠处死测定脑组织中含水量、伊文思蓝(EB)含量,采用实时荧光定量聚合酶链反应(qRT-PCR)法检测各组大鼠脑组织中水通道蛋白(AQP)-4、基质金属蛋白酶(MMP)-2、MMP-9 mRNAs在脑组织中的表达。采用Western blot检测各组大鼠脑组织中AQP-4、MMP-2及MMP-9蛋白的表达。结果模型组大鼠在脑损伤后均出现呼吸急促、心率加快等症状,格列本脲治疗后大鼠呼吸及心率逐渐下降恢复稳定状态,假手术组无明显病理现象;病理结果显示,模型组大鼠神经元水肿明显,格列本脲高、低剂量组大鼠神经元细胞体积亦增大,但病理损伤程度均低于模型组。模型组大鼠脑组织含水量及EB含量显著高于假手术组(P<0.05),水平活动及垂直活动均显著低于假手术组(P<0.05);格列本脲高剂量组和低剂量组脑组织含水量及EB含量均较模型组显著降低(P<0.05),水平活动及垂直活动均较模型组显著升高(P<0.05),且呈一定剂量依赖性;模型组大鼠脑组织中AQP-4、MMP-2和MMP-9 mRNA及蛋白的表达水平均显著高于假手术组(P<0.05);格列本脲高剂量组和低剂量组脑组织中AQP-4、MMP-2和MMP-9 mRNA及蛋白的表达水平均较模型组显著下调(P<0.05),呈一定剂量依赖性。结论格列本脲能改善脑外伤大鼠血脑屏障的通透性减轻创伤性脑水肿,并改
Objective To observe the effect of glibenclamide on brain trauma-induced brain edema in rats with traumatic brain injury and preliminarily explore its related molecular mechanism for the treatment of traumatic brain injury.Methods The traumatic brain injury model was established by Feeney′s free falling impact method.The modeling rats were divided into 3 groups(n=32 each):model group,glibenclamide low dose group(intraperitoneal injection of 5μg·kg-1 glibenclamide)and glibenclamide high dose group(intraperitoneal injection of 10μg·kg-1 glibenclamide).The other 32 rats were used as sham operation group(open the bone window only without impact processing,and the rest of the operation was the same with modeling group).The rats in model group and sham operation group were administered by intraperitoneal injection of equal amounts of dimethyl sulfoxide(DMSO)for continuous administration of 5 days.The basic situation of rats in each group after operation was observed.Eight rats in each group were executed at 6 h,1 d,3 d and 5 d,respectively after operation to determine the water content and content of Evans blue(EB)in brain tissues.Real time fluorescence quantitative polymerase chain reaction(qRT-PCR)method was used to detect the expressions of aquaporin-4(AQP-4),matrix metalloproteinase 2(MMP-2)in brain tissues and matrix metalloproteinase 9(MMP-9)mRNAs.Western blot method was used to detect the expressions of AQP-4,MMP-2 and MMP-9 proteins in brain tissues.Results In model group,the symptoms such as shortness of breath,rapid heart rate and so on appeared,and breathing and heart rate gradually decreased and restored to stable state after treatment of glibenclamide.There was no obvious pathological phenomenon in sham operation group.In model group,water content and EB content in brain tissues was significantly higher than that in sham operation group(P<0.05),and horizontal activities and vertical activities were significantly lower than those in sham operation group(all P<0.05).Water content and EB content of brai
作者
马喜明
王卫军
MA Xi-ming;WANG Wei-jun(Department of Pharmacy,Qinghai People's Hospital,Xining,Qinghai 810000,China)
出处
《中国临床研究》
CAS
2019年第3期404-409,共6页
Chinese Journal of Clinical Research
