α-硫辛酸对实验性自身免疫性脑脊髓炎大鼠模型干预的初步研究

Effect of α-lipoic acid on rats with experimental autoimmune encephalomyelitis

目的研究α-硫辛酸(α-LA)对实验性自身免疫性脑脊髓炎(EAE)大鼠模型干预的有效性,探讨α-LA临床治疗多发性硬化的可能性。方法Wistar大鼠30只,其中22只制作EAE模型,分为α-LA干预组(11只)及免疫组(11只),另8只为非免疫组。α-LA干预组大鼠于免疫当天开始每天1次腹腔注射α-LA(100mg/kg),至实验28d结束处死日止;免疫组及非免疫组大鼠每天腹腔注射等量0.9%氯化钠溶液。对各组大鼠进行神经功能缺损评分、病理学及免疫组织化学检查。结果α-LA干预组的EAE发病率为5/11,显著低于免疫组的9/11(P<0.01)。α-LA干预组大鼠免疫后第14天及第16～28天的神经功能缺损评分显著低于免疫组(P值均<0.05)。α-LA干预组大鼠脑组织切片脱髓鞘病灶数为(3.85±1.21)个,脊髓组织切片病灶数为(4.26±2.65)个,均显著少于免疫组的(9.09±5.61)和(14.45±5.10)个(P值均<0.05)。免疫组织化学髓鞘碱性蛋白(MBP)染色也显示,α-LA干预组病理切片的髓鞘松散、脱失明显轻于免疫组。结论α-LA能显著改善EAE大鼠的神经功能,干预EAE的发病。

Objective To explore the efficacy of α-lipoic acid（α-LA） in treating rat with experimental autoimmune encephalomyelitis（EAE）,and to discuss the feasibility of using α-LA for treatment of multiple sclerosis（MS）.Methods Twenty-two rats with EAE were randomly divided into the treatment group（n=11） and immunization group（n=11）;another 8 rats served as non-immunization controls（n=8）.The treatment group was given daily intraperitoneal α-LA（100 mg/kg） from the 1^st day of research till the 28^th day when the animals were sacrificed;the immunization group and non-immunization group received equal volume of normal saline.Meanwhile,we also observed the clinical neurological scores and the pathology,immunohistochemistry outcomes of all rats.Results The treatment group had a EAE incidence of 5（5/11）,which was significantly lower than that in the immunization group（9 [9/11],P〈0.01）.The clinical neurological score of the treatment group was significantly lower than that of the immunization group on the 14^th,16^th-28^th day（P〈0.05）.The demyelinating lesions were 3.85±1.21 in the brain and 4.26±2.65 in the spinal cord of the treatment group,which were significantly lower than those of the immunization group（9.09±5.61 in brain and 14.45±5.10 in the spinal cord,P〈0.05）.Immunohistochemistry examination showed that demyelinating lesions of the treatment group were obviously slighter than those of the immunization group.Conclusion α-LA can greatly improve the clinical neurological functions of rat EAE model,preventing the progression of EAE.