奥沙利铂化疗对小鼠行为及内侧前额叶皮层中少突胶质细胞前体细胞的影响  

Effects of oxaliplatin chemotherapy on behavior and oligodendrocyte precursor cells in the medial prefron‐tal cortex of mice

作　　者：岳亮 李坤 庞金卫 熊源长 YUE Liang;LI Kun;PANG Jinwei;XIONG Yuanchang(Department of Pain Management,the First Affiliated Hospital,Naval Medical University,Shanghai 200433,China;Department of Anesthesiology,the 985th Hospital of the Joint Logistic Support Force,PLA,Taiyuan 030001,Shanxi,China)

机构地区：[1]海军军医大学第一附属医院疼痛治疗科,上海200433 [2]解放军联勤保障部队第九八五医院 [3]解放军联勤保障部队第九八五医院麻醉科,太原030001

出　　处：《医学研究与战创伤救治》2025年第1期1-8,共8页Journal of Medical Research & Combat Trauma Care

基　　金：国家自然科学基金(81971048)。

摘　　要：目的探究奥沙利铂化疗对小鼠行为的影响,并进一步分析这种影响与小鼠内侧前额叶皮层(mPFC)中的少突胶质细胞前体细胞(OPCs)之间的潜在联系。方法构建奥沙利铂诱导的小鼠抑郁模型,采用随机数字表法将26只小鼠随机分为对照组和奥沙利铂组,每组13只小鼠。在每组中随机选取10只小鼠进行行为学实验,以评估其抑郁样行为,具体通过强迫游泳实验、糖水偏好实验和悬尾实验来完成,另外3只小鼠进行5-溴脱氧尿嘧啶核苷(Brdu)标记实验。在行为学试验结束后,每组随机取4只小鼠,应用免疫荧光技术检测小鼠mPFC中OPCs的密度和增殖情况。将来自SD大鼠的体外培养OPCs用随机数字表法分为对照和不同浓度奥沙利铂处理组(0.25、0.5、1、2μmol/L),每组4孔,应用免疫荧光技术检测体外大鼠OPCs的增殖情况。结果奥沙利铂组小鼠的强迫游泳实验中不动时间较对照组延长,蔗糖偏好指数较对照组降低,悬尾实验中不动时间较对照组延长,差异均有统计学意义(P<0.05)。第22天时,奥沙利铂组小鼠mPFC区内每平方毫米的OPCs数量及OPCs占总细胞数的比例较对照组明显减少(P<0.05)。第9天时,奥沙利铂组小鼠mPFC区OPCs每平方毫米的数量相较于对照组明显减少(P<0.05),奥沙利铂组小鼠mPFC区域中Brdu+OPCs占OPCs的比例相较于对照组显著减少(P<0.05)。体外实验显示,各浓度奥沙利铂Brdu+OPCs占OPCs的比例及Ki67+OPCs占OPCs的比例较对照明显减少,差异有统计学意义(P<0.01)。结论奥沙利铂化疗可诱导小鼠出现抑郁样行为,降低了小鼠mPFC中OPCs的密度,并抑制了其增殖,OPCs增殖受损与奥沙利铂化疗导致的抑郁样行为之间存在潜在的联系。Objective To investigate the effect of oxaliplatin chemotherapy on the behavior of mice,and to further analyze the potential relationship between this effect and oligodendrocyte precursor cells(OPCs)in the medial prefrontal cortex(mPFC)of mice.Methods A depression model was established in mice by the induction of oxaliplatin.Through random number table method,26 mice were randomly divided into control group and oxaliplatin group with 13 mice in each group.Ten mice in each group were randomly selected for behavioral experiments to assess depression-like behavior,which were completed through forced swimming test,sucrose preference test and tail suspension test.The remaining 3 mice in each group were used for 5-bromo-2´-deoxyuridine(Brdu)labeling experiments.After the behavioral experiment,4 mice were randomly selected from each group to detect the density and proliferation of OPCs in mPFC of mice by immunofluorescence technique.OPCs cultured in vitro from SD rats were divided into control groups and oxaliplatin treatment groups(0.25,0.5,1,2μmol/L)with different concentrations by random number table method,with 4 wells in each.The proliferation of OPCs in vitro rats was detected by immunofluorescence technique.Results The immovable time in oxaliplatin group was longer than that in control group in forced swimming test,the sucrose preference index was lower than that in control group,and the immovable time in tail suspension test was longer than that in control group,the differences were statistically significant(P<0.05).On day 22,the number of OPCs per square millimeter and the proportion of OPCs to total cell number in mPFC area of oxaliplatin group were significantly decreased compared with control group(P<0.05).On day 9,the number of OPCs per square millimeter in mPFC region of mice in oxaliplatin group was significantly reduced compared with control group(P<0.05),and the proportion of Brdu+OPCs in mPFC region of mice in oxaliplatin group was significantly reduced compared with control group(P<0.05).In vitro ex

关 键 词：奥沙利铂 抑郁 内侧前额叶皮层 少突胶质细胞前体细胞 

分 类 号：R979.1[医药卫生—药品]