α硫辛酸对实验性自身免疫性脑脊髓炎大鼠轴索损伤的保护作用

Effect ofα-thioctic acid on axonal injury in rats with experimental autoimmune encephalomyelitis

目的探讨α硫辛酸对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)大鼠轴索损伤的影响。方法选取36只Wistar大鼠,采用豚鼠全脊髓匀浆(guinea pig spinal cord homogenate,GPSCH)诱导免疫以建立EAE大鼠模型。EAE大鼠于第1次发病之日起分别给予生理盐水(EAE组)、100mg·kg-1·d-1α硫辛酸(LA组)、2mg·kg-1·d-1地塞米松(DXM组)进行腹腔注射,连续注射7d。统计各组大鼠复发率;采用Kono评分评估各组大鼠神经功能变化;采用组织病理学观察大鼠轴索损伤变化。结果EAE组、LA组和DXM组复发率分别为58.3%(7/12)、8.3%(1/12)、0;LA组和DXM组复发率均明显小于EAE组,组间比较差异有统计学意义(P<0.05);LA组与DXM组比较差异无统计学意义(P>0.05)。发病后7d、14d,LA组和DXM组神经功能评分均明显低于EAE组,组间比较差异有统计学意义(P<0.05);LA组与DXM组比较差异无统计学意义(P>0.05)。组织病理学结果显示,正常对照组轴索粗细均匀、走行方向一致、轴索的连续性完好;EAE组出现不同程度轴索改变,可见轴突肿胀、增粗、弯曲,着色不均,呈锯齿状或串珠状,不连续,甚至断裂,髓鞘结构层次紊乱;LA组轴索改变较EAE组明显减轻,但仍有少部分轴索肿胀、粗细不均、排列紊乱;DXM组轴索改变情况与LA组类似。结论α硫辛酸对EAE大鼠轴索损伤具有一定保护作用。

Objective To evaluate the effect ofα-thioctic acid on axonal injury in rats with experimental autoimmune encephalomyelitis（EAE）.Methods The study selected 36 Wistar rats,and guinea pig spinal cord homogenate（GPSCH）was used to establish EAE model rats.From this first seizure,the EAE model rats respectively were given to normal saline（EAE group）,α-thioctic acid 100mg·kg-1·d-1（LA group）and dexamethasone 2 mg·kg-1·d-1（DXM group）,continuously intraperitoneal injected for 7 d.The recurrence rate of different groups were recorded.Kono score was used to assess neurological function.The immunohistochemistry was adopted to observe the axonal injury.Results The recurrence rate of EAE group,LA group and DXM group were 58.3%（7/12）,8.3%（1/12）and 0.The recurrence rate of LA group and DXM group were significantly less than that of EAE group（P〈0.05）.After seizure 7dand 14 d,the neurological function score of LA group and DXM group were significantly less than that of EAE group（P〈0.05）.The normal control group showed axon even thickness direction in the same direction,the continuity of axon intact.EAE group manifested different degrees of axon change,visible axon swelling,enlargement,bending,uneven color,a serrated or beaded,discontinuous,even rupture,myelin sheath structure level disorder.Compared with EAE group,the axonal injury of LA group significantly reduced,but there were still a few axon swelling,uneven thickness,disordered arrangement.The axonal injury of DXM group was similar to LA group.Conclusionα-thioctic acid has certain protective effect on axonal injury of EAE rats.