不同低氧胁迫方式下SD大鼠急进高原模型的比较研究

Comparative study on SD rat models of rapid high-altitude entry under different hypoxia stress modes

目的对SD大鼠在高原实地和模拟高原环境这2种低氧胁迫方式下建立的急进高原模型进行比较研究,进而鉴定模拟高原实验舱的可靠性。方法将SD大鼠分别急进模拟高原动物实验舱(4000 m)或高原实地实验室(4010 m)来建立大鼠急进高原模型,在暴露24 h或72 h后采集并测定高原生理病理变化相关指标,主要包括血常规、血生化、血气、氧化损伤指标(超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px))、炎症指标(白细胞介素-1β(interleukin 1β,IL-1β)、γ干扰素(interferon-γ,IFN-γ)、单核细胞趋化蛋白1(monocyte chemotactic protein 1,MCP-1)和白细胞介素-6(interleukin 6,IL-6))、病理组织分析和低氧敏感基因(低氧诱导因子-1α(hypoxia inducible factor-1α,Hif-1α)和血管内皮生长因子A(vascular endothelial growth factor A,Vegfa))等,最终对结果进行差异性分析,得出差异性评估报告。结果相同海拔高度下,高原实地或模拟高原暴露72 h后均可以产生明显的肺部和脑部损伤。相同暴露时间下,动物机体的血常规、血生化和血气结果相近,炎症指标(IL-6,IL-1β,MCP-1和IFN-γ)、氧化损伤指标(MDA,SOD和GSH)和脑部低氧敏感基因(Hif-1α和Vegfa)等检测结果无显著性差异。但是,模拟72 h组的二氧化碳分压(partial pressure of carbon dioxide,PaCO_(2))和碱剩余(base excess,BE)显著高于其他低氧处理组、模拟72 h组的肺部低氧敏感基因(Hif-1α和Vegfa)与空白对照组无显著性差异,以及高原实地处理组脑系数显著高于模拟高原处理组等结果提示高原实地和模拟高原环境可能存在细微区别。结论模拟高原实验舱在4000 m海拔可成功建立急进高原动物模型,最优暴露时间应大于24 h但略短于72 h。模拟高原实验舱具有良好的可靠性,但条件允许情况下应尽量前往高原实地来建立急进高原动物模型。

Objective A comparative study was conducted on rapid high-altitude models established in SD rats under two hypoxic stress modes,namely,a high-altitude field and simulated high-altitude environment,to evaluate the reliability of the simulated high-altitude test chamber.Methods SD rats were placed in a simulated rapid high-altitude animal experimental chamber(4000 m)or rapid high-altitude field laboratory(4010 m)to establish a rapid high-altitude rat model.After 24 or 72 h of exposure,physiological and pathological indicators related to high-altitude changes were collected and measured,mainly routine blood parameters,blood biochemistry,blood gas,oxidative damage indicators(superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)),and inflammation indicators(interleukin 1β(IL-1β),interferon-γ(IFN-γ),monocyte chemotactic protein 1(MCP-1)and interleukin 6(IL-6)),and pathological tissue analysis and hypoxia sensitive gene(hypoxia inducible factor-1α(Hif-1α)and vascular endothelial growth factor A(Vegfa))testing were performed.Finally,differential analysis was conducted on the result to obtain a differential evaluation report.Results At the same altitude,both high-altitude field and simulated high-altitude exposure for 72 h caused significant lung and brain damage.Under the same exposure time,the routine blood parameter,blood biochemistry,and blood gas result for the rats were similar.There were no significant differences in the detection of inflammation indicators(IL-6,IL-1β,MCP-1,and IFN-γ),oxidative damage indicators(MDA,SOD,and GSH),or hypoxia-sensitive gene expression(Hif-1αand Vegfa)in the brain.However,partial pressure of carbon dioxide(PaCO2)and base excess(BE)were significantly higher in the simulated-72 h group than the other treatment group.The lung hypoxia-sensitive genes(Hif-1αand Vegfa)in the simulated-72 h group showed no significant expression difference with control group,and the brain coefficient of the high-altitude field treatment group was significantly higher than that of the simulated high-altitude treatment group.These result indicate that there may be slight differences between models prepared in high-altitude field and simulated high-altitude environments.Conclusions The simulated high-altitude animal experimental chamber can successfully establish a rapid high-altitude animal model.The simulated altitude can be appropriately increased on the basis of 4000 m.If an altitude of 4000 meters is used,the exposure time should be greater than 24 h but slightly shorter than 72 h.The simulated high-altitude experimental module has good reliability,but it is advisable to use plateaus for on-site experiments as much as possible,if conditions permit.