环胞霉素A对局部脑缺血海马细胞外液氨基酸及微环境变化的影响

Effect of CsA on amino acid contents and microenvironment of hippocampal extracellular fluid after local cerebral ischemia in tree shrews

目的观察环胞霉素A(CsA)对局部脑缺血时海马细胞外液氨基酸及微环境的影响,并探讨可能的神经元保护机制。方法将实验动物(树鼩)分为3组:假手术组于舌下静脉注射孟加拉红生理盐水,不照射;脑缺血组注射孟加拉红生理盐水循环15 min后进行光化学反应形成局部脑缺血;实验治疗组于缺血后6 h一次性舌下静脉注射CsA(40 mg/kg),上述各组于24h时间点测量氨基酸及微环境指标。结果给CsA后,天冬氨酸、谷氨酸及甘氨酸均降低,而γ-氨基丁酸升高,与脑缺血组相比差异有统计学意义(P<0.01)。而pH、PO2及HCO3-均增高,与脑缺血组相比差异有统计学意义(P<0.05),PCO2变化不明显。脑缺血后,海马组织有明显的缺血坏死表现,给CsA后,缺血坏死明显减轻。结论选择缺血后6 h"治疗时间窗"注射CsA,可有效改善海马细胞外液兴奋性与抑制性氨基酸比例和微环境,保护神经元功能。

Objective To observe the effect of cyclosporin A（CsA）on amino acid and micro environement,and to explore the possible mechanisms of neuron protection.Methods To establish three groups：sham,ischemia and treatment groups.The experimental animals were pretreated by CsA（40 mg/kg） at 6 h after occlusion.The focal thrombotic cerebral ischemia was formed by photochemistry-induced technology in tree shrews.Amino acids and pH,PCO2,PO2 and HCO3-of the above groups were detected by blood gas analyzer and HPLC-PITC technology respectively.Results In CsA group,the contents of Asp,Glu and Gly was decreased,but GABA increased,and there were notable difference compared with the ischemic group（P〈0.01）.The most hippocampal neurons were normal;few was defective after pretreatment with CsA.Conclusion CsA could improve contents of amino acid and microenvironment after occlusion in choosing the 6 h ＂therapy window＂.CsA probably protect neuron by changing contents of excitatory amino acid or inhibitory amino acid through different mechanisms.