线粒体保护剂对异氟醚麻醉老年小鼠海马线粒体功能和突触可塑性的影响

摘要

目的：观察线粒体保护剂 SS-31对异氟醚麻醉老年小鼠线粒体功能和突触可塑性的影响。方法老年雄性 C57BL/6小鼠48只随机均分为四组(n=12)：氧气+生理盐水组(CN 组)、氧气+SS-31组(CS 组)、异氟醚+生理盐水组(IN 组)和异氟醚+SS-31组(IS 组)。根据分组,于氧气或异氟醚吸入前30 min 腹腔注射等容生理盐水(CN、IN 组)或 SS-31(5 mg/kg,CS、IS 组),于气体吸入2 h 后取小鼠海马组织。提取线粒体检测电子传递链复合物Ⅰ~Ⅳ酶活性、三磷酸腺苷(ATP)和线粒体膜电位(MMP)水平,组织匀浆检测突触可塑性相关蛋白突触蛋白1(synapsin-1)、突触后密度蛋白95(PSD-95)、NMDA 受体2A (NMDAR2A)、NMDAR2B、钙调蛋白依赖的蛋白激酶Ⅱα(CaMKⅡα)和 CaMKⅡβ的含量。结果与 IN 组比较,IS 组复合物Ⅰ酶活性、ATP 和 MMP 水平升高,synapsin-1和 PSD-95含量增加,NMDAR2B、CaMKⅡα和 CaMKⅡβ含量降低(P <0.05),而复合物Ⅱ~Ⅳ酶活性及 NMDAR2A 含量差异无统计学意义。结论线粒体保护剂 SS-31可改善异氟醚麻醉所致老年小鼠海马线粒体及神经元突触可塑性损伤。%Objective To observe the effects of mitochondrial protectant on hippocampal mito-chondrial function and synaptic plasticity in isoflurane-anesthesia aged mice.Methods Forty-eight fif-teen-month-old male C57BL/6 mice were equally divided into 4 groups (n=12):oxygen+normal sa-line (group CN),oxygen+SS-31 (group CS),isoflurane+normal saline (group IN),and isoflurane+SS-31 (group IS).SS-31(5 mg/kg)or normal saline was intraperitoneally administered with a vol-ume of 0.4 ml/kg 30 min before gas inhalation.After two hours gas inhalation,the hippocampus was removed to determine complex Ⅰ-Ⅳ activities,adenosine triphosphate (ATP)and mitochondrial membrane potential (MMP)levels from isolated mitochondria,and measure the content of synapsin-1,PSD-95,NMDAR2A,NMDAR2B,CaMKⅡα and CaMKⅡβ.Results Compared with the group IN,complex Ⅰ activity,ATP and MMP levels were increased,synapsin-1 and PSD-95 were up-regu-lated,whereas NMDAR2B,CaMK Ⅱα and CaMK Ⅱβ were down-regulated in the group IS (P <0.05).No significant difference was observed in the complex Ⅱ-Ⅳ activities and NMDAR2A expres-sion.Conclusion Mitochondrial protectant SS-31 attenuates isoflurane-induced mitochondrial dysfunc-tion and neuron synaptic plasticity impairments in aged mice.