硫柳汞对早产大鼠行为学及免疫球蛋白变化的影响

Effect of thiomersalate exposure on the behaviour and humoral immunity of premature rats

目的 探讨硫柳汞对早产大鼠行为学及免疫球蛋白的影响.方法 根据表面积转换法,以人用疫苗中常用的硫柳汞水平为参照,分别选取1、2、3、4倍剂量并转换成大鼠适合剂量（32.8、65.6、98.4和131.2μg/kg）,按体质量分别一次性注射给孕20 d剖腹出生第1天的大鼠（早产）,同时选注射9g/L盐水组作为对照.并于注射后第44-48天通过水迷宫实验检测大鼠空间学习记忆功能,且测量注射后第49天大鼠血和脑脊液中免疫球蛋白水平.结果 水迷宫实验：131.2 μg/kg组的学习功能比9g/L盐水组明显减低（P＜0.001）;65.6μg/kg、98.4μg/kg和131.2 μg/kg组记忆功能明显较9 g/L盐水组减低（P均＜0.001）.脑脊液与血液中免疫球蛋白的变化：不同暴露剂量硫柳汞引起的脑脊液与血液免疫球蛋的改变存在显著性差异,其中98.4 μg/kg、131.2 μg/kg组各免疫球蛋白与9 g/L盐水组比较差异均有统计学意义（P均＜0.01）.免疫球蛋白与学习功能变化的直线相关关系：血液中IgG、IgA、IgE与学习功能变化具有相关关系（r=0.36、0.47、0.50,P均＜ 0.05）,IgG、IgA、IgE、IgM与记忆功能变化呈相关性（r=-0.39、-0.43、-0.49、-0.38,P均＜0.05）.脑脊液中IgG、IgA、IgE、IgM与大鼠学习和记忆功能变化具有相关关系（r=0.48、0.59、0.54、0.41,P均＜0.05;r=-0.39、-0.61、-0.57、-0.44,P均＜0.05）.结论 随暴露硫柳汞浓度增加,早产大鼠体液免疫和行为学产生持续变化.

Objective To discover the influence of thiomersalate exposure on the behavior and humoral immunity of premature rats.Methods According to common thiomersalate dose of vaccine used in human,the surface conversation method was used to change the dose to 1,2,3,4 times for rats（32.8,65.6,98.4 and 131.2 μg/kg）,and the thiomersalate was separately injected to the gluteus maximus of premature rats respectively,which were delivered on the 20th day of gestation by cesarean for the injection on day 1 （premature）.Simultaneously,saline was injected to the control group.On day 44 to 48 after injection,the Morris water maze test was used to evaluate the spatial learning and memory abilities of rats and on the post-injection day 49,immunoglobulin content in rat blood and cerebrospinal fluid was measured.Results The spatial learning abilities of rats in 131.2 μg/kg group and the memory abilities in 65.6 μg/kg,98.4 μg/kg and 131.2 μg/kg group were significantly weaker than those in 9 g/L saline group（all P ＜0.001）.The immunoglobulin content in blood and cerebrospinal fluid changed in different groups exposed to thiomersalate.The levels of IgG,IgA,IgE,IgM in 98.4 μg/kg group and 131.2 μg/kg group rose significantly higher than those in 9 g/L saline group（all P ＜ 0.01）.Analysis of rectilinear correlation between the immunoglobulin and learning abilities of rats revealed that IgG,IgA,IgE levels in the blood were correlated with the spatial learning abilities （r =0.36,0.47,0.50,all P ＜ 0.05） and the levels of IgG,IgA,IgE,IgM in blood were rectilinear correlated with the memory abilities of rats （r =-0.39,-0.43,-0.49,-0.38,all P ＜ 0.05）.In rats＇cerebrospinal fluid,IgG,IgA,IgE,IgM levels were rectilinear correlative with both the spatial learning and memory abilities （r =0.48,0.59,0.54,0.41,all P＜0.05;r=-0.39,-0.61,-0.57,-0.44,all P＜0.05）.Conclusion With the dose ofthiomersalate increased,the learning and memory and humoral immunity are sustained damaged for premature rats.