摘要
目的探讨托吡酯(TPM)对大鼠脑缺血再灌注损伤的神经保护作用及其机制。方法将健康30只雄性SD大鼠随机分为假手术组、缺血再灌注组和TPM干预组。用线栓法建立大鼠脑缺血再灌注模型,TPM干预组给予TPM80mg/kg腹腔注射,2次。缺血再灌注24h时进行神经功能评分、TTC染色法测量梗死体积、高效液相色谱分析法测定脑组织谷氨酸(Glu)及γ-氨基丁酸(GABA)的含量;免疫组化法检测GABAA受体阳性表达。结果(1)与缺血再灌注组比较,TPM干预组神经功能评分明显增高(P<0.01),脑梗死体积减少(P<0.05);(2)TPM干预组缺血侧脑皮质Glu含量显著低于缺血再灌注组(P<0.01),与假手术组比较差异无显著性;GABA含量显著高于假手术组和缺血再灌注组(均P<0.01);(3)TPM干预组缺血侧脑皮质GABAA受体阳性细胞数显著高于缺血再灌注组(P<0.01)。结论TPM对脑缺血再灌注损伤有神经保护作用,其机制可能为TPM降低兴奋性递质Glu水平、增加抑制性递质GABA的释放及GABAA受体的表达。
Objective To investigate the neuroprotective effects of Topiramate (TPM) on rat brain with ischemia-reperfusion damage and its mechanisms. Methods The 30 male SD rats were randomly assigned to sham operated group, ischemia-reperfusion group and TPM treated group. The cerebral ischamia and reperfusion model was made by suture occlusion of right middle cerebral artery (MCAO). Rats in TPM treated group were intraperitoneally injected TPM (80 mg/kg) twice. At 24 h following onset of MCAO, the nerve function score was evaluated with Neurological Grading Scale. The infarction volume was measured with TIC staining. The contents of glutamate (Glu) and gamma-aminobutyric acid (GABA) of cerebral cortex were tested by the high performance liquid chromatography with fluorescent detection. GABAA receptors were observed by immunohistochemistry. Results ( 1 ) Compared with the ischemia-reperfusion group, the Neurological Grading Scale of TPM treated group was significantly higher ( P 〈 0. 01 ), and its infarct volume reduced (P 〈 0.05 ); (2) Rats in TPM treated group had a lower Glu concentration of the cerebral cortex in ischemic hemisphere than those in ischemia-reperfusion group ( P 〈 0.01 ), and an elevated GABA concentration than those in ischemia-reperfusion group and sham operated group ( all P 〈 0. 01 ). ( 3 ) The numbers of GABAA positive cell in TPM treated group were significantly increased than those in the ischemiareperfusion group ( P 〈 0.01 ). Conclusions By inhibiting the exitotoxicity of Glu, increasing endogenous GABA and expression of GABAA receptors, TPM may reduce the brain damage after cerebral ischemia-reperfusion and has neuroprotective effects.
出处
《临床神经病学杂志》
CAS
北大核心
2007年第1期38-41,共4页
Journal of Clinical Neurology
关键词
脑缺血
托吡酯
神经保护
cerebral ischemia
Topirmate
neuroprotection