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[干扰素-β和静脉注射免疫球蛋白治疗实验性周围神经病的机制]

[Therapeutic mechanisms of interferon-beta and intravenous immunoglobulin for experimental peripheral neuropathy].

作者信息

Gao Yu-xing, Li Shu-lan, Han Xiu-zhen, Sun Yan, Yao Chun-mei

机构信息

Department of Pediatric Neurology, Shandong Provincal Hospital, Jinan 250021, China.

出版信息

Zhonghua Er Ke Za Zhi. 2007 Aug;45(8):574-8.

Abstract

OBJECTIVE

To explore the therapeutic mechanisms of interferon-beta (IFN-beta) and intravenous immunoglobulin (IVIG) for experimental peripheral neuropathy induced by Campilobacter jejuni (Cj) lipopolysaccharide (LPS).

METHOD

Forty healthy Wistar rats weighing 205 - 230 g were divided into IFN-beta, IVIG, IFN-beta plus IVIG and control groups. After the immune neuropathy was induced in the rats by Cj LPS, IFN-beta (1.3 microg/kg) was given by subcutaneous injection to the rats every other day for 6 weeks; IVIG [400 mg/(kg x d)] was given to the rats for five days, every other week for two times and IFN-beta [1.3 microg/(kg x d)] and IVIG [400 mg/(kg x d)] were given to the rats on the same days. Meanwhile, the control group was given PBS. The sera were collected in the 2nd, 4th and 6th week after therapy, the titers of anti-GM(1) IgG, MMP-9 and TNF-alpha in sera of immunized rats were measured by ELISA; histological study of sciatic nerve was performed and IgG on sciatic nerve was detected by immunohistochemistry in the 6th week.

RESULTS

(1) There were no significant differences in titers of anti-GM(1) IgG, MMP-9 and TNF-alpha among the 3 therapeutic groups and control group after therapy for 2 weeks (P > 0.05). (2) The titers of anti- GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta and IVIG group after therapy for 4 weeks (P > 0.01) and there were no significant differences in titers of antibody among the 3 therapeutic groups (P > 0.05); the titers of MMP-9 or TNF-alpha in the IFN-beta and IVIG group were lower than those of the IFN-beta group or the IVIG group (P < 0.05). (3) The titers of anti-GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta with IVIG group after therapy for 6 weeks (P > 0.01); the IFN-beta with IVIG group had much lower levels of all indexes than the IFN-beta group or the IVIG group (P < 0.01).

CONCLUSION

IFN-beta and IVIG showed therapeutic effects on immune peripheral neuropathy through inhibiting the humoral and cellular immunity simultaneously in the peripheral neuropathy induced by CJ LPS, treatment with combined IFN-beta and IVIG was more effective.

摘要

目的

探讨β-干扰素(IFN-β)和静脉注射免疫球蛋白(IVIG)对空肠弯曲菌(Cj)脂多糖(LPS)诱导的实验性周围神经病的治疗机制。

方法

将40只体重205 - 230 g的健康Wistar大鼠分为IFN-β组、IVIG组、IFN-β加IVIG组和对照组。用Cj LPS诱导大鼠免疫性神经病后,IFN-β(1.3μg/kg)每隔一天皮下注射给大鼠,共6周;IVIG[400mg/(kg·d)]给大鼠连续5天,每隔一周给药2次,IFN-β[1.3μg/(kg·d)]和IVIG[400mg/(kg·d)]在同一天给药。同时,对照组给予PBS。治疗后第2、4和6周采集血清,用ELISA法检测免疫大鼠血清中抗GM(1)IgG、基质金属蛋白酶-9(MMP-9)和肿瘤坏死因子-α(TNF-α)的滴度;在第6周对坐骨神经进行组织学研究,并用免疫组化法检测坐骨神经上的IgG。

结果

(1)治疗2周后,3个治疗组与对照组之间抗GM(1)IgG、MMP-9和TNF-α的滴度无显著差异(P>0.05)。(2)治疗4周后,对照组抗GM(1)IgG、MMP-9或TNF-α的滴度明显高于IFN-β组、IVIG组或IFN-β与IVIG组(P>0.01),3个治疗组之间抗体滴度无显著差异(P>0.05);IFN-β与IVIG组MMP-9或TNF-α的滴度低于IFN-β组或IVIG组(P<0.05)。(3)治疗6周后,对照组抗GM(1)IgG、MMP-9或TNF-α的滴度明显高于IFN-β组、IVIG组或IFN-β联合IVIG组(P>0.01);IFN-β联合IVIG组所有指标水平均明显低于IFN-β组或IVIG组(P<0.01)。

结论

在Cj LPS诱导的周围神经病中,IFN-β和IVIG通过同时抑制体液免疫和细胞免疫对免疫性周围神经病显示出治疗作用,IFN-β与IVIG联合治疗更有效。

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