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目的探讨干扰素β(IFN-β)和丙种球蛋白(IVIG)对空肠弯曲菌(CJ)脂多糖(LPS)诱导的免疫性周围神经病的治疗机理。方法健康 Wister 大鼠40只,体重205～230 g,用 CJ LPS 成功诱导出免疫神经病后,随机分为 IFN-β组、IVIG 组、IFN-β联合 IVIG 组和正常对照组。IFN-β组:每隔1 d,给予 IFN-β 1.3μg/kg 皮下注射,共6周。IVIG 组:每隔2周,静脉注射 IVIG400 mg/(kg·d),连续5 d,共2次。IFN-β和 IVIG 联合组:IFN-β和 IVIG 的给药时间分别同 IFN-β组和 IVIG 组。对照组:以 PBS 溶液(200μl/只)替代 IFN-β或 IVIG。分别于治疗前和治疗后第2、4、6周取血,用 ELISA方法检测血清中抗 GM_1 IgG、MMP-9和 TNF-α滴度,第6周取坐骨神经进行病理学检查和免疫组化检测坐骨神经上特异性 IgG 结合。结果 (1)3个治疗组治疗2周时,抗 GM_1 IgG、MMP-9和 TNF-α滴度与对照组比较差异无统计学意义(P>0.05)。(2)3个治疗组治疗4周时,抗 GM_1 IgG、MMP-9和TNF-α滴度明显低于对照组(P<0.01);3组之间抗 GM_1 IgG滴度比较差异无统计学意义(P>0.05);联合治疗组 MMP-9和 TNF-α水平低于单一治疗组(P<0.05)。(3)3个治疗组治疗6周时,抗 GM_1 IgG、MMP-9和 TNF-α滴度、神经原纤维病变率和神经上特异性 IgG 结合明显低于对照组(P<0.01);各指标联合治疗组明显低于单一治疗组(P<0.01)。结论 IFN-β和 IVIG 通过对特异性体液免疫和细胞免疫的同时抑制,达到对 CJLPS 诱导的免疫性周围神经病的治疗作用;IFN-β和 IVIG 联合应用疗效更佳。
Objective To investigate the therapeutic mechanism of interferon β (IFN-β) and gammaglobulin (IVIG) on immune peripheral neuropathy induced by Campylobacter jejuni (CJ) lipopolysaccharide (LPS). Methods Forty healthy Wister rats weighing 205-230 g were randomly divided into IFN-β group, IVIG group, IFN-β combined with IVIG group and normal control group after CJ LPS successfully induced immune neuropathy. IFN-β group: IFN-β 1.3 μg / kg was given subcutaneously every other day for 6 weeks. IVIG group: intravenous IVIG 400 mg / (kg · d) every 2 weeks for 5 consecutive days for 2 times. Combination of IFN-β and IVIG: IFN-β and IVIG were administered to IFN-β and IVIG groups respectively. Control group: IFN-β or IVIG was replaced with PBS solution (200 μl / mouse). Blood samples were collected before treatment and at 2, 4, and 6 weeks after treatment. Serum anti-GM1 IgG, MMP-9 and TNF-α titers were detected by ELISA. At the 6th week, sciatic nerve was taken for pathological examination and immunohistochemistry Detection of specific IgG binding on the sciatic nerve. Results (1) There was no significant difference in anti-GM1 IgG, MMP-9 and TNF-α titers between the three treatment groups at 2 weeks and the control group (P> 0.05). (2) The titers of anti-GM1 IgG, MMP-9 and TNF-α in the three treatment groups were significantly lower than those in the control group at 4 weeks (P <0.01). There was no significant difference in anti-GM1 IgG titers between the three groups (P> 0.05). The levels of MMP-9 and TNF-α in the combined treatment group were lower than those in the single treatment group (P <0.05). (3) The anti-GM1 IgG, MMP-9 and TNF-α titers, neurofibrillary lesion rates and neuro-specific IgG binding in the three treatment groups were significantly lower than those in the control group (P <0.01) The index combination therapy group was significantly lower than the single treatment group (P <0.01). Conclusion IFN-β and IVIG can achieve the therapeutic effect on CJLPS-induced autoimmune peripheral neuropathy by inhibiting the specific humoral and cellular immunity simultaneously. The combined effect of IFN-β and IVIG is better.