不同菌型空肠弯曲菌免疫诱发大鼠变态反应性周围神经病的对比研究

目的　明确空肠弯曲菌（CJ）两种不同血清型（Pen19和Pen43）与格林-巴利综合征（GBS）的关系。方法　分别用CJ-Pen19和CJ-Pen43菌体灭活粗抗原加完全福氏佐剂并充分乳化后，经皮下多点注射反复致敏60只Wistar大鼠，对两种菌株空肠弯曲菌(Pen19和Pen43)进行分组对比研究。结果　（1）Pen19和Pen43免疫后，两组大鼠血清IgG类抗CJ抗体滴度均增高，并于3～4周后稳定于高峰水平；（2）Pen19组坐骨神经病变率（60.0%）及原纤维病变率（17.7%）均比Pen43组（分别为10.0%和0.5%）和生理盐水组（分别为5.0%和0.5%）明显增高（P＜0.001），后两组间比较差异无显著意义（P＞0.05）；（3）Pen19组原纤维病变类型（轴索变性∶髓鞘脱失）比较，初期以轴索变性为主，比值为3.4%∶0.7%，后期则以髓鞘脱失占优势，比值为5.3%∶24.1%；（4）Pen19组大鼠血清IgG类特异性抗CJ抗体水平与神经轴索变性率呈正相关(r=0.801)，而与脱髓鞘率关系不大(r=0.353)，IgM的水平与轴索变性及髓鞘脱失的发生均无关（r分别为0.253和0.281）。结论　（1）CJ对周围神经免疫性损伤能力与其血清类型密切相关；（2）CJ-Pen19所诱发的实验性周围神经病变病理类型初期以轴索变性为主，后期髓鞘脱失占优势；（3）特异性IgG类抗CJ抗体在轴索变性的发生中可能起重要作用。

Immunological mechanism of peripheral neuropathy induced by Campylobacter jejuni-Incidences of experimental peripheral neuropathy induced by Pen19 and Pen43

Recent studies have suggested that Campylobacter jejuni (CJ) may be the most common pathogen causing Guillain-Barre syndrome (GBS). Fifteen to seventy-five percent of patients with GBS had had a recent CJ infection. The serotypes of CJ isolated from stool usually are Penner (Pen) 19, Pen4, Pen41, and so on. Although some serotypes of CJ have been proved to associate with GBS, the directly evidence from the animal model is needed. Objective　 To clarify the association of peripheral neuropathy with GBS by using the different serotypes of CJ to immunize Wistar rats respectively. Methods　Sixty Wistar rats were divided into three groups: CJ-Pen 19 group, CJ-Pen43 group and normal saline control group. Each rat was immunized repeatedly with Freund′s adjuvant and inactivation antigen of CJ-Pen19, Pen43 and normal saline, respectively. The serum titers of specific anti-CJ antibodies were detected by ELISA. The pathologic examination of sciatic nerves was performed at different time points: 1, 2, 3, 4 and 5 weeks, respectively after the immunization. Results　(1) Compared with the normal saline group, the serum titer of anti-CJ IgG elevated after immunization and sustained at a higher level after the 3rd-4th week in the CJ-Pen19 and Pen43 groups of rats. (2) The incidences of pathologic nerves and fibers in CJ-Pen19 group (60.0% and 17.7%, respectively) were much higher than those of CJ-Pen43 group (10.0% and 0.5%, respectively) and of normal saline group (5.0% and 0.5%, respectively, P＜0.001). There was no significant difference between CJ-Pen43 and normal saline groups (P＞0.05). (3) At the initial stage, the type of pathologic fibers was mostly axon degeneration. The ratio of axon degeneration to demyelination was 3.4% to 0.7%. But at advanced stage, the proportions of demyelination increased rapidly and the ratio of axon degeneration to demyelination was 5.3% to 24.1%. (4) There was a positive correlation between the antibody titer of specific anti-CJ IgG and the incidence of axon degeneration (r=0.801) compared with the demyelination. There was no correlation between the IgM level and the incidence of axon degeneration or demyelination (r=0.253 and 0.281, respectively). Conclusions　 (1) The incidence of experimental peripheral neuropathy might depend on CJ serotypes; (2) The majority of pathologic fibers showed axonal degeneration at the initial stage and remarkable demyelination at the later stage. (3) The specific anti-CJ IgG antibody might act as an important pathogenic factor in the process of axon degeneration.