BAY 60-6583对MK-801介导小鼠脑髓鞘损伤的保护作用

The Protective Effects of BAY 60-6583 Against MK-801 Induced Cerebral Myelin Damage Model Mice

目的探究腺苷受体A2B激动剂BAY 60-6583对精神分裂症(SCZ)模型小鼠脑髓鞘损伤的保护作用。方法36只6周龄ICR雄性小鼠随机分为对照组(Control组)、模型组(MK-801组)、模型+BAY 60-6583组(MK-801+BAY组),每组12只。连续14 d腹腔注射MK-801[0.6 mg·(kg·d)^(-1)]制备SCZ小鼠模型,造模7 d后隔天腹腔注射BAY 60-6583[80μg·(kg·d)^(-1)]。旷场、悬尾实验观察动物焦虑和抑郁样行为改变;坚牢蓝(LFB)染色观察髓鞘着色范围改变;电镜观察髓鞘超微结构改变;Western blot检测髓鞘碱性蛋白(MBP)表达水平改变;免疫荧光检测少突胶质谱系细胞增殖改变。结果MK-801组小鼠较Control组小鼠表现出明显的焦虑、抑郁样行为,胼胝体LFB着色少而浅,髓鞘板层结构松散且出现局灶性溶解,MBP蛋白表达水平降低,Ki67^(+)/Olig2^(+)细胞数量减少(P均<0.05)。与MK-801组小鼠相比,MK-801+BAY组小鼠焦虑和抑郁样行为明显改善,胼胝体LFB着色呈深蓝色丝状物,髓鞘板层结构致密且局灶性溶解明显改善,MBP蛋白表达水平上调,Ki67^(+)/Olig2^(+)细胞数量升高(P均<0.05)。结论BAY 60-6583可改善模型小鼠焦虑和抑郁样行为及髓鞘损伤程度,可能与其影响少突胶质谱系细胞增殖有关。

Objective To investigate the protective effects of the adenosine receptor A2B agonist BAY 60-6583 against the brain myelin damage of schizophrenia(SCZ)model mice.Methods Thirty-six ICR male mice of 6-week old were randomly divided into three groups:control group(Control group),model group(MK-801 group),model+BAY 60-6583 group(MK-801+BAY group),with 12 mice per group.Mice were injected intraperitoneally with MK-801[0.6 mg·(kg·d)^(-1)]once a day for 14 consecutive days,and BAY 60-6583[80μg·(kg·d)^(-1)]was performed every 2 days after 7 days of injection MK-801.In the open field test and tail suspension test,the animal’s anxiety and depression-like behavioral changes were observed.luxol fast blue(LFB)was applied for the change in myelin staining.The ultrastructure of the myelin sheath,the expression level of myelin basic proteins MBP,and the proliferation of oligodendrocyte lineage cells were all studied using transmission electron microscopy,Western blot,and immunofluorescence,respectively.Results The MK-801 group showed obvious anxiety and depression-like behaviors,the light blue LFB-staining area in the corpus callosum,the loose and focal dissolution of the myelin lamella,the decreased MBP expression level,and the reduced Ki67^(+)/Olig2^(+)cell numbers in comparison with the control group(P all<0.05).Compared with the MK-801 group,in the MK-801+BAY group,the anxiety and depression-like behaviors were significantly improved,the LFB-staining area in the corpus callosum was dark blue,the myelin lamellar structure was dense and the focal dissolution of myelin was significantly improved,the expression level of MBP protein was up-regulated,and the number of Ki67^(+)/Olig2^(+)cells was increased(P all<0.05).Conclusion BAY 60-6583 may alleviate anxiety and depression-like behaviors as well as myelin damage in model mice,possibly by influencing the proliferation of oligodendrocyte line cells.