丹参酮ⅡA对高原缺氧大鼠认知功能障碍的影响

The effects of Tanshinone ⅡA on high altitude hypoxia-induced cognitive deficits in rats

目的:探讨丹参酮ⅡA(TanⅡA)对高原缺氧(HH)大鼠认知功能障碍的预防作用及其可能机制。方法:将54只成年雄性SD大鼠分为对照组(control)、高原缺氧组(HH)和TanⅡA治疗组(TanⅡA)。通过低压氧舱模拟高原环境,低氧28 d造模。利用Morris水迷宫试验评估大鼠认知功能;利用膜片钳技术记录海马长时程增强(LTP),评估各组大鼠认知功能;取海马组织低温匀浆,利用试剂盒检测其SOD、GSH-Px、GSH、MDA等氧化应激相关指标,评价各组大鼠海马氧化应激状态。结果:HH组大鼠在水迷宫试验中逃避潜伏期较control组延长(P <0. 05),缺氧大鼠在目标象限游动时间百分比下降;与HH组相比,TanⅡA治疗组逃避潜伏期缩短(P <0. 05),在目标象限游动时间百分比升高(P <0. 05),HH组LTP幅度较对照组显著降低(P <0. 05),TanⅡA干预后,海马LTP较模型组明显增强(P <0. 05);相对control组,HH组大鼠海马SOD、GSH-Px、GSH水平显著降低(P <0. 05)、MDA水平明显升高(P <0. 05),TanⅡA治疗组可显著逆转上述结果(P <0. 05)。结论:TanⅡA可通过降低高原缺氧大鼠海马氧化应激水平、提高其清除氧自由基能力保护海马神经元,进而减轻大鼠认知功能障碍。

Objective:The purpose of the study was to investigate the effect of tanshinoneⅡA(TanⅡA)on cognitive deficits induced by high altitude hypoxia(HH)and the possible mechanism.Methods:54 male SD rats were assigned to one of the 3 groups including control group(control),high altitude hypoxia group(HH)and TanⅡA treatment group(TanⅡA).Cognitive function in 3 groups was tested by the water maze task.Hippocampal long-term potentiation(LTP)was measured using patch-clamp recordings in rat brain slices.Glutathione(GSH)and maleic dialdehyde(MDA)content in the hippocampal homogenate were measured;The activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the hippocampal homogenate were detected.Results:Hypobaric hypoxia can cause severe cognitive deficits,and TanⅡA could attenuate HH-induced cognitive deficits.Hippocampal LTP inhibition induced by HH were significantly improved by administration of TanⅡA.HH can markedly increase content of MDA,decrease content of GSH and the activities of SOD and GSH-PX in the hippocampal homogenate,which can be reversed by TanⅡA.Conclusion:TanⅡA reveals therapeutic potential for HH-induced cognitive deficits,which is most likely related,at least in part,to its anti-oxidative stress actions in hippocampus.