丹参酮ⅡA对放射性脑损伤小鼠的神经保护作用及机制研究

Protective effect of Tan ⅡA on brain injury induced by radiation in mice and its molecular mechanism

目的:探讨丹参酮ⅡA(Tan ⅡA)对小鼠放射性脑损伤的神经保护作用及其可能机制。方法:小鼠144只分为空白对照组、单纯照射组和各用药组。比较各组小鼠Morris水迷宫实验结果、脑组织含水量、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性水平、脑细胞凋亡率、脑脊液ATP含量以及脑组织P2X7受体表达水平。结果:单纯照射组小鼠平均潜伏期时间和寻找平台的路径总长均明显长于空白对照组,20mg/kg和40mg/kg丹参酮ⅡA组明显短于单纯照射组;单纯照射组脑含水量明显高于空白对照组,20mg/kg和40mg/kg丹参酮ⅡA组明显低于单纯照射组;单纯照射组海马组织中SOD活性和MDA含量分别较空白对照组显著降低和升高,而20mg/kg和40mg/kg丹参酮ⅡA组与单纯照射组相比SOD活性升高、MDA含量则降低;单纯照射组脑细胞凋亡率和明显高于空白对照组,20mg/kg和40mg/kg丹参酮ⅡA组明显低于单纯照射组;单纯照射组脑脊液ATP含量明显高于空白对照组,20mg/kg和40mg/kg丹参酮ⅡA组明显低于单纯照射组;单纯照射组小鼠脑组织P2X7受体蛋白的表达较空白对照组升高,而20mg/kg和40mg/kg丹参酮ⅡA组较单纯照射组表达下降。结论:丹参酮ⅡA可能通过抑制ATP介导的P2X7R活化炎症介质释放和自由基累积,进而减少细胞凋亡和脑水肿,起到保护放射性脑损伤所致的神经损害作用。

Objective： To investigate the neuroprotective effects of Tan ⅡA on radiation-induced brain injury in mice and its possible molecular mechanism.Methods： 144 mice were divided into control group,radiation group and the treatment group.Then,the ATP content in cerebrospinal fluid,the expression level of P2X7 receptor,MDA content and SOD activity,the apoptosis rate of brain cells,the brain water content and data in Morris water maze test were compared among groups.Results： ATP content in CSF in the radiation group was significantly higher than that in the control group,while that in 20mg/kg and 40mg/kg Tan ⅡA groups were significantly lower than that in radiation group（ P 〈 0.05）; The expression of P2X7 in brain tissue of radiation group compared with control group was increased,while the 20mg/kg and40mg/kg Tan ⅡA groups compared with the irradiation group decreased（ P 〈 0.05）; SOD activity and MDA content in the radiation group were compared with control group significantly decreased and increased respectively,while the SOD activity in 20mg/kg and 40mg/kg Tan ⅡA groups increased and MDA content decreased significantly compared with radiation group（ P 〈 0.05）; The apoptosis of brain cells and brain water content in radiation group were significantly higher than that of the control group,those in 20mg/kg and 40mg/kg Tan ⅡA groups were significantly lower than that in the radiation group（ P 〈 0.05）; The average latency and path length of mice to find the platform were significantly longer than that in the control group,those in 20mg/kg and 40mg/kg Tan ⅡA groups were significantly shorter than that in the simple irradiation group（ P 〈 0.05）.Conclusion： Tan ⅡA may inhibit the release of ATP,which mediated P2X7 receptor,then inflammatory mediators increased and free radical accumulation,further protected the nerve damage caused by radiation brain injury.