1-溴丙烷致大鼠认知功能障碍的炎性机制研究  

The study on inflammatory mechanism of cognitive dysfunction induced by 1-bromopropane in rats

作　　者：单姗 王增金[1,2] 赵秀兰 Shan Shan;Wang Zengjin;Zhao Xiulan(School of Public Health,Shandong University,Jinan 250012,China;Shandong Provincial Qianfoshan Hospital,Jinan 250014,China)

机构地区：[1]山东大学公共卫生学院,济南250012 [2]山东省千佛山医院,济南250014

出　　处：《中华行为医学与脑科学杂志》2022年第3期212-219,共8页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金(81172708,81872654)。

摘　　要：目的采用1-溴丙烷(1-bromopropane,1-BP)诱导大鼠认知功能障碍,探讨神经炎性反应在1-BP致中枢神经毒性中的作用。方法60只清洁级雄性Wistar大鼠按照随机数字表法分为对照组(Control组)、1-BP组、吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)组(PDTC组)和PDTC+1-BP组,每组15只。1-BP组和1-BP+PDTC组大鼠灌胃800 mg/kg的1-BP,Control组和PDTC组大鼠给予等体积玉米油,1次/d,连续灌胃12 d;PDTC组和PDTC+1-BP组在灌胃30 min后腹腔注射100 mg/kg的PDTC,Control组和1-BP组注射等体积生理盐水,1次/d,连续干预12 d。实验第7~12天每组随机取10只大鼠采用Morris水迷宫检测大鼠神经行为学指标,定位航行实验检测大鼠的学习记忆能力,空间探索实验评价大鼠对空间位置的记忆能力。行为学实验结束后,每组随机选取10只大鼠处死,分离大脑前额叶皮质,采用Western blot检测NF-κB的激活情况,qRT-PCR检测TNF-α及IL-1βmRNA水平;每组剩余5只大鼠经体内灌注固定后,取大脑制作冷冻切片,采用免疫组化染色和尼氏染色观察胶质细胞激活及神经元损伤情况。采用SPSS 20.0对实验数据进行统计学处理,游泳总距离和逃避潜伏期数据采用重复测量方差分析,穿越平台次数及其他数据采用单因素方差分析,进一步两两比较采用Turkey’s检验。结果Morris水迷宫结果显示,各组大鼠游泳总距离的组别和训练时间交互作用显著(F=3.762,P<0.05)。简单效应分析显示,1-BP组大鼠第1~4天的游泳总距离均长于Control组(均P<0.05),而PDTC+1-BP组大鼠第1~4天的游泳总距离均短于1-BP组(均P<0.05)。各组大鼠逃避潜伏期的组别和训练时间交互作用显著(F=6.541,P<0.01)。简单效应分析显示,与正常Control组相比,1-BP组大鼠的逃避潜伏期在第1~4天均长于Control组(均P<0.05),而PDTC+1-BP组的逃避潜伏期在第1~4天均短于1-BP组(均P<0.05)。空间探索实验结果显示,四组大鼠的穿越平台次�Objective To observe the role of neuroinflammation in cognitive dysfunction induced by 1-bromopropane(1-BP)in rats.Methods Male Wistar rats were randomly divided into control group,1-BP group,pyrrolidine dithiocarbamate(PDTC)+1-BP group and PDTC group,with 15 rats in each group.Rats in 1-BP group and PDTC+1-BP group were given 800 mg/kg 1-BP by gavage,and rats in control group and PDTC group were given equal volume corn oil once a day for 12 days;rats in PDTC group and PDTC+1-BP group were intraperitoneally injected with 100 mg/kg PDTC 30 minutes after gavage,while rats in control group and 1-BP group were injected with equal volume of normal saline once a day for 12 days.From the 7th to 12th day of the experiment,ten rats in each group were randomly selected and subjected to Morris water maze test for detect the cognitive function.In the positioning navigation test,the learning ability of rats was evaluated by the escape latency and total swimming distance respectively.In the space exploration experiment,the memory ability of experimental animals was evaluated by the number of times crossing the target platform.After the experiment,ten rats were sacrificed,the cerebral prefrontal cortex was harvested.The cytosolic and nuclear NF-κB expression and phosphorylation were detected by Western blot,the mRNA levels of TNF-αand IL-1βwere detected by qRT-PCR.After cardiac perfusion fixation,the brains of 5 rats were taken to make frozen sections for immunohistochemical staining and Nissl staining.SPSS 20.0 software was used for statistical analysis,repetitive measurement deviation analysis was used for the analysis of the swimming distance and the escape latency in positioning navigation test,One-way ANOVA was used for the analysis of the number of times crossed the target platform in spatial probe test and other data.Tukey's test was used for Post hoc comparison.Results The results of Morris water maze showed that there was significant interaction between group and training time in the total swimming distance of rats

关 键 词：1-溴丙烷 吡咯烷二硫代氨基甲酸盐 NF-ΚB 认知功能 神经炎症 大鼠 

分 类 号：R114[医药卫生—卫生毒理学] R749.1[医药卫生—公共卫生与预防医学]