目的:观察七氟烷预处理对缺氧小鼠脑损伤的影响及其可能机制.方法:将60只雄性C57BL/6J小鼠,随机分为对照(C)组、缺氧(H)组、2%七氟烷预处理30min组(S1+H组)、2%七氟烷预处理60min组(S2+H组)和4%七氟烷预处理30min组(S3+H组),每组10只.缺氧即持续吸入O2体积分数为(6.5±0.1)%的氮氧混合气体24h构建缺氧模型;预处理即以O2体积分数为(21.0±0.5)%的氮氧混合气体为载气,分别吸入2%七氟烷30min、2%七氟烷60min和4%七氟烷30min,洗脱15min后进行缺氧处理.用光学显微镜及透射电子显微镜(TEM)观察海马CA1区形态学改变;比色法检测血清乳酸脱氢酶(LDH)活性;ELISA测定脑组织促红细胞生成素(EPO)和血管内皮生长因子(VEGF)含量;同时测定脑组织丙二醛(MDA)含量及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)活性.结果:缺氧24h后,光镜下可见海马CA1区细胞水肿或固缩;各预处理组病理改变轻于H组.TEM下S2+H组细胞超微结构最为完整.H组血清LDH活性及脑组织EPO、VEGF、MDA含量显著高于C组,脑组织的SOD及GPx活性较C组明显降低.七氟烷预处理后血清LDH活性及脑组织EPO、VEGF含量较H组降低,以S2+H组最为显著;脑组织MDA含量及SOD活性降低,而GPx活性有所升高.结论:七氟烷预处理能减轻缺氧引起的脑组织损伤,其机制可能与调节抗缺氧蛋白合成及降低氧化应激有关.%AIM:To observe the effects of sevoflurane preconditioning on brain injury in hypoxic mice and its possible mechanism. METHODS:Male C57BL/6J mice were randomly divided into control (C) group, hypoxia (H) group,2% sevoflurane preconditioning for 30 min + hypoxia(S1+H) group,2% sevoflurane preconditioning for 60 min+hypoxia (S2+H) group and 4% sevoflurane preconditioning for 30 min + hypoxia(S3+H) group. The hypoxia model was established by continuous inhalation of(6.5±0.1)% O2for 24 h. The sevoflurane preconditioning treatments,S1,S2 and S3,were conducted by inhalation of 2% sevoflurane for 30 min,2% sevoflurane for 60 min and 4% sevoflurane for 30 min,respectively,with the carrier of(21.0±0.5)% O2,followed by washout for 15 min and then hypoxia treatment. The histological changes of the hippocampal CA1 area were observed under light microscope and transmission electron micro-scope(TEM),and serum lactate dehydrogenase (LDH) activity was measured by colorimetric method. Furthermore, the protein levels of erythropoietin (EPO) and vascular endothelial growth factor(VEGF) in brain tissue homogenate were ex-amined by ELISA,and the content of malondialdehyde(MDA) and the activity of superoxide dismutase(SOD) and gluta-thione peroxidase(GPx) were measured by microplate reader. RESULTS:After hypoxia for 24 h,cell edema or pyknosis in the hippocampal CA1 area was observed in H group. Sevoflurane preconditioning reduced hypoxic injury, and the cell ultrastructure under TEM was significantly improved in S2+H group. Compared with C group,the serum LDH activity and the levels of EPO,VEGF and MDA in brain tissues were significantly increased in H group,while the activity of SOD and GPx decreased. After sevoflurane pretreatment,the serum LDH activity and the levels of EPO and VEGF in brain tissues were lower than those in H group,and the most significant difference was observed in S2+H group. Moreover, the MDA content and SOD activity decreased,and the GPx activity increased in the sevoflurane preconditioning groups. CONCLU-SION:Sevoflurane preconditioning attenuates brain injury in hypoxic mice by regulating antihypoxic protein synthesis and reducing oxidative stress.
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