丁基苯酞对肌萎缩侧索硬化转基因小鼠神经保护作用的初步探讨  

A preliminary study of the neuroprotective effect of dl-3-n-butylphthalide in a transgenic mouse model of amyotrophic lateral sclerosis

作　　者：冯新红[1] 袁伟[2] 彭英[3] 刘明生[4] 崔丽英[4] 

机构地区：[1]大连医科大学附属第二医院神经内科,116027 [2]北京大学人民医院创伤骨科,100044 [3]中国医学科学院药物研究所,100050 [4]中国医学科学院北京协和医院神经内科,100730

出　　处：《中国神经免疫学和神经病学杂志》2013年第1期20-23,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家自然科学基金资助项目(No.30971002;No.30911120496)

摘　　要：目的观察丁基苯酞对肌萎缩侧索硬化(ALS)转基因小鼠腓肠肌运动单位及脊髓前角运动神经元数目的影响,并初步探讨其神经保护作用。方法将雌性ALS-SOD1G93A转基因小鼠分为溶剂对照组和丁基苯酞组,野生型同窝ALS-SOD1G93A小鼠为野生组。丁基苯酞组自小鼠发病日起每天按体质量60mg/kg给予丁基苯酞灌胃,溶剂对照组和野生组予等同体积的植物油灌胃。应用统计学法运动单位数目估计测定腓肠肌运动单位的数目。焦油紫染色观察脊髓前角运动神经元。结果野生型组、溶剂对照组和丁基苯酞组小鼠腓肠肌复合肌肉动作电位(CMAP)平均波幅分别为(24.30±0.30)、(12.80±7.15)和(18.20±7.27)mV,野生型组与溶剂对照组间比较有统计学差异(P<0.01),丁基苯酞组与溶剂对照组比较无统计学差异(P=0.209);野生型组、溶剂对照组和丁基苯酞组小鼠腓肠肌的运动单位数目分别为(135.80±8.64)、(63.20±31.87)、(110.50±9.68)个,脊髓前角大的运动神经元数目分别为(28.50±6.36)、(9.50±2.92)、(14.80±2.64)个,溶剂对照组小鼠腓肠肌的运动单位数目和脊髓前角大的运动神经元数目均较野生型组明显减少,与溶剂对照组相比,丁基苯酞治疗能延缓腓肠肌和脊髓前角运动单位丢失的速度(均P<0.01)。结论丁基苯酞对ALS转基因小鼠的保护作用可能是通过减缓脊髓前角运动神经元和腓肠肌运动单位的丢失而实现。Objective To investigate the effect of dl-3-n-butylphthalide （DL-NBP） in the transgenic mouse model of amyotrophic lateral sclerosis （ALS） （ALS-SOD169aa）. Methods ALS-SOD1-93A female mice were divided into the DL-NBP group and the vehicle control group; the wild-type group was composed of wildtype littermate mice. The DL-NBP group received 60 mg DL-NBP/ （kg day）, the vehicle control group and the wild-type group received the same volume of peanut oil daily. Gastrocnemius muscle motor unit number was measured by a modified statistical method of motor unit number estimation （MUNE）. A total of 200 serial transverse sections （10 μm thick） of spinal cords （L4-5） were stained with 1% cresyl violet to count the number of spinal cord large anterior horn motor neurons. Results The average compound muscle action potentials of the wild-type group, the vehicle control group and the DL-NBP group were （24.30----＋-_ 0.30）, （12.80 ± 7.15） and （18.20±7.27） mV. The motor unit numbers of the 3 groups were （135.80±8.64）, （63.20±31.87）, （110.50±9.68） and the numbers of spinal cord large anterior horn motor neurons were （28.50±6.36）, （9.50 ± 2.92）, （14.80± 2.64）. There were significant decreases in MUNE and spinal cord large anterior horn motor neurons in vehicle control ALS-SOD1G93a mice. 60 mg/kg DL-NBP significantly slowed the rate of MUNE reduction （P 〈 0.01）. Conclusions DL-NBP treatment significantly delayed motor unit reduction and motor neuron loss of ALS-SOD1^G93A mice. These results suggest that DL-NBP might be a promising compound in the treatment of ALS.

关 键 词：丁基苯酞 肌萎缩侧索硬化 运动单位数目估计 

分 类 号：R745.4[医药卫生—神经病学与精神病学]