超氧化物歧化酶1 G41S和G41D在小鼠中枢神经系统过表达对其运动功能影响的初步研究

Effect of Superoxide Dismutase 1 G41S and G41D Overexpression in the Central Nervous System of Mice on Motor Function

目的探究超氧化物歧化酶1(SOD1)的SOD1G41S和SOD1G41D基因对小鼠运动功能的影响。方法实验小鼠分为对照组(转染空的重组腺相关病毒)、SOD1WT组、SOD1G41S组和SOD1G41D组,均n=12。利用重组腺相关病毒基因过表达的特点,构建携带SOD1WT、SOD1G41S和SOD1G41D的重组腺相关病毒,分别注射至小鼠双侧侧脑室和鞘内,建立转基因小鼠模型。1个月后测量对照组、SOD1WT组、SOD1G41S组和SOD1G41D组小鼠的体重,并通过握力测试、悬尾实验、转棒疲劳实验和旷场实验评估各组小鼠的运动功能。结果成功构建了携带SOD1WT、SOD1G41S、SOD1G41D的重组腺相关病毒,不同相关病毒处理1个月对小鼠的体重无明显影响。握力测试显示SOD1G41S组和SOD1G41D组握力值显著低于SODWT组(P<0.001)而高于对照组(P<0.01);但SOD1G41S组与SOD1G41D组比较差异无统计学意义(P>0.05)。转棒疲劳实验中,SOD1G41D组坠落潜伏期显著低于SOD1WT组和SOD1G41S组(P<0.05),但3组坠落潜伏期均高于对照组(P<0.01)。旷场实验中,SOD1WT组和SOD1G41S组的运动距离显著高于对照组(均P<0.05);SOD1G41D组运动距离与对照组比较(P>0.05)。各组实验小鼠在中心区域停留时间比较差异无统计学意义(均P<0.05)。结论SOD1WT、SOD1G41S和SOD1G41D在中枢神经系统过表达均能提高重组腺相关病毒模型小鼠的运动能力,其能力大小依次为SOD1WT、SOD1G41S和SOD1G41D。

Aim To investigate the effects of SOD1G41S and SOD1G41D overexpression on motor function in mice.Methods The mice were divided into a control group(transfected empty recombinant adeno-associated virus),a SOD1WT group,a SOD1G41S group and a SOD1G41D group,the number of mice was 12 in each group.The SOD1WT,SOD1G41S and SOD1G41D recombinant adeno-associated virus were built and injected through bilateral lateral ventricle combination with intrathecal to transfect the central nervous system widely in mice.A month later,the body weight of mice of the four groups whose central nervous system overexpressed SOD1WT,SOD1G41S,SOD1G41D and no exogenous SOD1 control were measured and the motor function were evaluated by grip strength test,tail suspension test,rod fatigue test and open field test.Results The recombinant adeno-associated virus carrying SOD1WT,SOD1G41S and SOD1G41D was successfully constructed.In the behavioral test,the mice of the four groups were no significant difference in body weight,and the pathological reflex was normal.In the grip strength test,the grip strength of SOD1G41S and SOD1G41D group was significantly lower than that of SODWT group(P<0.001).However,they were higher than that of the control group(P<0.01).There was no difference between SOD1G41S and SOD1G41D group.In the rod fatigue test,the fall latency of SOD1G41D group was significantly lower than that of SOD1WT group and SOD1G41S group(P<0.05),but the fall latency of SOD1WT,SOD1G41S and SOD1G41D groups was significantly higher than that of the control group(P<0.01).In the open feild test,the movement distance of SOD1WT group and SOD1G41S group was significantly higher than that of the control group(P<0.05),and the movement distance of SOD1G41D group was no difference when compared with the control group(P>0.05).The residence time in the central region between the each group was no significant difference(all P>0.05).Conclusion The overexpression of exogenous SOD1WT,SOD1G41S or SOD1G41D in the central nervous system could improve the motor ability of mice.The improvement of motor ability was as following in turn:SOD1WT,SOD1G41S and SOD1G41D.