化学预处理对低氧预适应模型小鼠的影响

Effects of chemical pretreatment on hypoxic preconditioned mice

背景:低氧诱导因子1α调节一些增加抗低氧耐受的基因的表达。氯化钴是一种能够稳定低氧诱导因子1α的化学试剂。目的:检测氯化钴预处理对急性重复低氧小鼠的影响。方法:Balb/C小鼠随机分为预处理组和对照组,实验前3h,两组分别注射氯化钴和生理盐水后,分别进行0次(正常对照组),1次,4次缺氧暴露,随即分别取海马组织进行指标检测。结果与结论:预处理组缺氧暴露1次对低氧耐受时间显著高于对照组缺氧暴露1次,预处理组缺氧暴露1次,4次低氧耐受时间差异无显著性意义。对照组中缺氧暴露4次组低氧诱导因子1的DNA结合活力显著高于缺氧暴露1次组和正常对照组,组间比较差异有显著性意义。预处理组中缺氧暴露1次组低氧诱导因子1的DNA结合活力显著高于正常对照组(P<.01),缺氧暴露4次组低氧诱导因子1的DNA结合活力急剧下降,显著低于缺氧暴露1次组和正常对照组。对照组促红细胞生成素和血管内皮生长因子mRNA在缺氧暴露1次组和缺氧暴露4次组升高,各组间比较差异有显著性意义(P<0.05)。预处理组促红细胞生成素和血管内皮生长因子mRNA表达组间比较差异无显著性意义。提示氯化钴预处理能够提高低氧耐受时间,降低低氧预适应诱导的耐受时间及低氧诱导因子1DNA结合能力。

BACKGROUND：Hypoxia-inducible factor-1 α（HIF-1α） regulates the expression of genes which increase resistance to hypoxia tolerance.CoCl2 is a chemical reagent that can stabilize HIF-1α.OBJECTIVE：To detect the effects of CoCl2 pretreatment on acute repetitive hypoxic exposure of mice.METHODS：Balb/c mice were randomly divided into chemical pretreatment group and normal group.At 3 hours before treatment,the mice in the two groups were respectively injected with CoCl2 and normal saline.After that,the mice in the two groups were subjected to hypoxic exposure for 0 run（normal control group）,1 run,and 4 runs,respectively.Subsequently,hippocampi of mice were removed immediately after the exposure for index detection.RESULTS AND CONCLUSION：The tolerance time after one-time hypoxic exposure in the chemical pretreatment group was higher than that in the control group,but there was no significant difference in four times hypoxic exposure between the chemical pretreatment and control groups.HIF-1 DNA binding activity of the four times hypoxic exposure subgroup in the control group was significantly higher than that of the one-time hypoxic exposure subgroup in the chemical pretreatment group and the normal control group.There was significant difference in each group.HIF-1 DNA binding activity of the one-time hypoxic exposure subgroup in the chemical pretreatment group was obviously higher than that in the normal group（P0.01）.In the control group,erythropoietin and vascular endothelial growth factor mRNA level in the one-time hypoxic exposure and four times hypoxic exposure subgroups showed increased.Each group had significant difference（P0.05）.There was no significant difference in erythropoietin and vascular endothelial growth factor mRNA levels among the chemical pretreatment group.These results suggest that CoCl2 chemical pretreatment can improve the tolerance time in hypoxic exposure,and thereby reduce induction of tolerance after hypoxic preconditioning and HIF-1 DNA binding activity.