钙蛋白酶抑制剂calpeptin对大鼠海马脑片缺氧无糖损伤的保护作用

目的通过观察电生理学和神经元凋亡的变化,研究钙蛋白酶抑制剂calpeptin对大鼠离体海马脑片缺氧无糖损伤的保护作用。方法40片SD大鼠海马脑片随机分为两组:对照组和calpeptin组。根据人工脑脊液中calpeptin的浓度,再细分为1μmol.L-1组、10μmol.L-1组、100μmol.L-1组和200μmol.L-1组,每组8片脑片。采用细胞外记录技术观察calpeptin对大鼠离体海马脑片在缺氧无糖条件下顺向群峰电位(orthodromicpopulationspikes,OPS)及缺氧损伤电位(hypoxicinjurypotential,HIP)变化的影响,采用TUNEL法观察缺氧无糖损伤后海马脑片CA1区锥体细胞凋亡情况及calpeptin对它的影响。结果10μmol.L-1组、100μmol.L-1组和200μmol.L-1组HIP出现率及海马CA1区锥体细胞层凋亡细胞数减少,OPS恢复率和OPS恢复程度与对照组比较提高。而10μmol.L-1组、100μmol.L-1组和200μmol.L-1组之间各项指标差异无显著性。结论(10～200)μmol.L-1calpeptin可以减轻大鼠海马脑片的缺氧无糖损伤,其机制可能与calpeptin减少海马CA1区神经元凋亡有关。

Protective effects of calpain inhibitor calpeptin on hypoxia/glucose deprivation injury in rat hippocampal slices

Aim To investigate effects of calpain inhibitor calpeptin against hypoxia/glucose deprivation injury in rat hippocampal slices.Methods Forty hippocampal slices were randomly divided into two groups:Control group and calpeptin group.Calpeptin group then divided again into 1 μmol·L-1 group,10 μmol·L-1 group,100 μmol·L-1 group and 200 μmol·L-1 group according to the concentration of calpeptin in ACSF_ OGD(n=8 per group).By using electrophysiology method,changes of OPS and HIP during hypoxia/glucose deprivation process and effects of different concentration of calpeptin on it were observed.We also observed the neuronal apoptosis in hippocampal CA1 region after hypoxia/glucose deprivation and effects of different concentration of calpeptin on it.Results The HIP appearance rate and neuronal apoptosis in hippocampal CA1 region of 10 μmol·L-1 group,100 μmol·L-1 group and 200μmol·L-1 group significantly reduced,the OPS recovery amplitude and OPS recovery rate significantly increased,and every index among 10 μmol·L-1 group,100 μmol·L-1 group and 200 μmol·L-1 group had no significant difference.Conclusion(10～200)μmol·L-1 calpeptin improved the hypoxia/glucose deprivation induced brain injury of rat hippocampal slices and the mechanism might be related to the inhibition of the neuronal apoptosis by calpeptin.