他克莫司对多发性硬化大鼠髓鞘碱性蛋白的动态变化及影响

摘要

目的 探讨他克莫司(FK506)对多发性硬化(MS)大鼠髓鞘碱性蛋白检测的动态变化及影响.方法 将试验动物随机分为两组,对照组(10只)予以实验性自身免疫性脑脊髓炎(EAE)+生理盐水组;研究组(12只)在EAE诱导的第1～7天,每日腹腔内注射剂量为1 mg/kg的FK506,其中急性发作期8只,缓解期 4只.检测研究组和对照组周围血和脑脊液髓鞘碱性蛋白(MBP)的水平,并动态观察应用他克莫司治疗前及治疗后不同时间MBP的变化情况.结果 研究组血清和脑脊液中的MBP水平均显著高于对照组(P ＜ 0.05).且两组脑脊液中的MBP水平均显著高于血清中MBP水平(P ＜ 0.05).研究组大鼠急性发作期及缓解期血清及脑脊液中MBP水平分别明显高于对照组(P ＜ 0.01),且大鼠急性发作期MBP水平血清及脑脊液中均分别显著高于MS缓解期(P ＜ 0.01).且大鼠脑脊液MBP和血清MBP水平呈正相关(r = 0.562,P ＜ 0.01).12只大鼠予以他克莫司腹腔注射后,治疗后的第3天及治疗后第7天血清和脑脊液MBP水平均较治疗前明显降低,且脑脊液MBP 水平较血清MBP水平降低更明显(P ＜ 0.01).结论 通过检测周围血和MBP的水平,并动态观察应用他克莫司治疗前及治疗后MBP的变化情况,一方面对判断MS预后、病情严重程度和临床诊断具有重要的临床意义,另一方面可能为预防多发性硬化的临床复发提供一种有效的新药提供指导依据.%Objective To explore the impact of the dynamic changes of tacrolimus for multiple sclerosis rat myelin basic protein detection. Methods Experimental animals were randomly divided into two groups, the control group were given the EAE + saline group, a total 10, study group in EAE induced daily intraperitoneal injection dose for 1 mg/kg FK506 from 1 to 7 days, a total of 12 acute exacerbation of 8 rats, 4 rats in remission. We examined the level of the blood and cere-brospinal fluid myelin basic protein (MBP) and dynamic observation for 12 cases MS rats (study group) and 10 normal healthy subjects (control group). Results MBP (research group) in serum and cerebrospinal fluid were significantly higher than that of the normal control group (P < 0.05). And MBP in the cerebrospinal fluid of two groups were significantly higher than the serum MBP level (P < 0.05). The serum and CSF MBP level of acute exacerbation and remission period of MS rats in the research group were significantly higher than that in the control group (P < 0.01), and MBP in serum and cerebrospinal fluid of acute exacerbation MS were respectively significantly higher than MS rats in remission (P < 0.01). In addition to the conventional basis for symptomatic 12 MS rates after admission tacrolimus treatment, after treatment 3 days and 7days, MBP level in the serum and CSF was significantly lower than before treatment, compared with serum,MBP levels in the cerebrospinal significantly decreased (P < 0.01). Conclusion Dynamic observation MBP the change by detecting the level of peripheral blood and MBP and the application of tacrolimus the secretary before treatment and after treatment on the one hand, to judge MS prognosis, the severity of the disease and the clinical diagnosis has importantthe clinical significance, on the other hand, it may be an effective new drug for the prevention of multiple sclerosis clinical recurrence provide the basis for guiding.