【作者】 杨承志；

【导师】 徐忠信；

【作者基本信息】 吉林大学 ， 神经病学， 2004， 硕士

【摘要】 吉兰－巴雷综合征（GBS）是以周围神经和神经根的脱髓鞘及小血管周围淋巴细胞和巨噬细胞的炎性反应为病理特点的自身免疫病，其病因还不完全清楚，大部分患者病前有感染史或疫苗接种史。分子模拟机制认为，GBS 的发病是由于病原体某些组分与周围神经组分相似，机体免疫系统发生错误的识别，产生自身免疫性 T 细胞和自身抗体，并针对周围神经组分发生免疫应答，引起周围神经髓鞘脱失。目前，其治疗主要包括支持对症和病因治疗，病因治疗的目的是调节机体免疫系统，消除致病性因子对神经的损害，并促进神经再生。最早的病因治疗应用的是糖皮质激素，近年来，血浆交换、亲和吸附、静脉注射免疫球蛋白等疗法在临床应用日趋广泛，并取得了较好的疗效。其中，静脉注射免疫球蛋白（IVIG）由于其操作简便，疗效肯定，是目前应用最有前景的药物。尽管有人报道糖皮质激素治疗 GBS 无效，但动物试验表明激素对 EAN 疗效确切。因此，目前临床仍未完全放弃应用激素治疗 GBS。本研究观察了免疫球蛋白联合激素治疗重症 GBS 的疗效，并与单用激素治疗进行比较，通过观察临床见效时间、临床作用效果特别是对呼吸麻痹的影响等方面综合评价其疗效，同时测定了部分患者治疗前后肌电图变化，计算运动神经传导速度的改变。 对 1998 年 1 月至 2004 年 1 月收治的 67 例临床确诊的 GBS 患者进行回顾性分析：对照组 35 例（其中男 14 例，女 21 例，年龄 12～62 岁，平均 27.6±6.8 岁；8 例累及呼吸肌，6 例气管切开）。确诊后即在支持治疗基础上应用地塞米松 10mg 每日一次静滴，7 天后减量；同时对不伴呼吸麻痹患者予地塞米松 5mg 鞘内注射，隔 3 天一次，共三次。治疗组 32 例（其中男 12 例，女 20 例，年龄 12～68 岁，平均 28.3±7.2 岁；9 例累及 37<WP=43>呼吸肌，3 例气管切开）。确诊后即在对照组治疗基础上加用免疫球蛋白（哈尔滨生化制品研究所生产，2.5g/支）0.4g/kg 体重每日一次静滴，静滴速度 3～4ml/min，连用 5 天。治疗前及治疗 7、14、21 天分别依照 Hughes量表进行功能评价临床分级，比较两种治疗方法的临床分级评分改善情况及临床见效时间。治疗后 21 天，对其临床疗效按以下标准进行评定：痊愈：脱离呼吸机，肌力恢复至 4＋级以上，生活能自理；有效：达不到痊愈标准，但病情明显好转；无效;经治疗病情无任何好转或更重。对部分患者在入院 1 周后及治疗 4 周后进行肌电图检查。治疗前后临床分级比较和临床见效时间等及临床痊愈率、有效率等数据应用 PC.SPSS 软件进行统计学分析。 两组病例年龄、性别、发病后距治疗时间、病情按 Hughes 量表分级均未发现统计学差异（P>0.05）。两组病人均已除外严重感染、结核、糖尿病等慢性病及严重脏器功能不全情况。两组治疗前后临床分级评分比较：对照组和治疗组病人病情在治疗前按 Hughes 功能量表进行评价两组无显著差异（P>0.05），而在 7、14、21 天时比较则有显著差异（14 天时P<0.01，7、21 天时 P<0.02）。两组临床见效时间评定：观察两组病人按Hughes 功能量表进行评价功能改善 1 级和 2 级的时间，并进行比较，治疗组病人 Hughes 评分改善 1 级和 2 级的时间明显短于对照组。两组比较，有显著性差异（P<0.01）。两组临床疗效评定：对照组有 6 例患者，治疗组有 3 例患者在治疗 2 周后临床症状改善不明显而自动出院，在本研究中作无效处理。治疗组痊愈率为 62.50%，对照组痊愈率为 37.14%，两者有显著差异。治疗组总有效率为 90.63%，对照组总有效率为 82.85%，虽然治疗组略高于对照组，但无统计学意义。治疗组呼吸困难平均持续时间及气切后恢复自主呼吸时间短于对照组，气管切开少于对照组。在入院 1 周后进行肌电图检查发现 MCV 减慢的病人 4 周后复查可见免疫球蛋白治疗 38<WP=44>后 MCV 恢复快于激素治疗。由于观察例数较少，对 IVIG 治疗伴呼吸困难病人的疗效及 MCV 的变化情况未进行统计学分析。两组均未见严重不良反应。 IVIG 治疗 GBS 的机制尚不完全清楚，可能与以下因素有关：（1）影响抗体。IVIG 含有具有不同特异性的特异性抗体和抗特异性抗体，有结合并中和致病性自身抗体的潜能，因而能阻断自身抗体与自身抗原的相互反应。IVIG 的抗特异性抗体还可能通过对 B 细胞施加负性信号影响抗体产物。IVIG 还能够加速内源性致病性 IgG 的分解代谢，降低致病性自身抗体的水平。（2）抑制超抗原，阻止超抗原触发的细胞毒性 T 细胞的活化和克隆扩增，干扰 T 细胞的抗原识别。（3）阻止补体结合并防止膜溶解性攻击性复合体（MAC）形成。（4）通过饱和、转化或下调 Fc 受体的亲和力而诱导巨噬细胞的 Fc 受体阻断，使致敏巨噬细胞失去功能。（5）影响细胞因子如 IL－1、IL－8、IL－6 和 TNF－α，影响 Th1和 Th2型 T 细胞，并能影响单核细胞释放细胞因子，因此而发挥抗炎作用。（6）通过间接作用使髓鞘修复。IVIG 还具有局部作用，对 CSF 有渗透性。因为血－神经屏障在神更多还原

【Abstract】 Guillain-Barre Syndrome(GBS), i.e, acute inflammatory demyelinatingpolyneuropathies, is an autoimmune disease characterized by demyelinating inperipheral nerves and nerve roots and inflammatory reaction on lymphocyteand megaphocyte. It,s etiology remains not very clear, most of the patientshave a infection history of upper respiratory tract or diarrhea. Some has ahistory of vaccinating. According to the molecular mimicry mechanism,because some components of the pathogen are similar to that of peripheralnerves, the human,s immunity system cannot discern it correctly, then excretesauto-immunity T cell and auto-antibodies and responses to the components ofthe PNS, causing the demyelinating on peripheral nerves. Nowadays, themainstay treatment is the causal treatment which based on supportingtreatment, that is, to regulate body,s immunity system, eliminate pathogenicfactors and promote regenerating of the nerve and remyelinating of the sheath.The glucocorticosteroid is the earliest medicine applied to GBS. Recently,plasma exchange, immunoadsorption and intravenous immunoglobulin aregradually applied and have manifested a better effect. IVIG, because it is easyto use and has a confirmed effect, is the most popular medicine for GBS now.Although someone has reported that glucocorticosteroid was useless to GBS,the animal experiments show that glucocorticosteroid is effective to EAN. Soglucocorticosteroid is still applied to GBS extensively. Our research observed 40<WP=46>the effect of combining glucocorticosteroid and intravenous immunoglobulinon treating severe GBS and compared it to that which only glucocorticosteroidwas applied then gave it a comprehensive evaluation. From Jan. of 1998 to Jan. of 2004, 67 severe patients who receivedtreatment in our department were admitted in this study. All patients wereclinically diagnosed GBS. Glucocorticosteroid was given to 35 cases. Afterdiagnosed, the 35 patients received intravenous DXM 10mg/d for 7 days onthe base of supportive treatment, then reduced the dosage gradually. At thesame time, intrathecally DXM 5mg applied to those who had no dyspneaevery 3 days, totally 3 times. 32 cases received IVIG(0.4mg/kg/d, totally 5days, produced by Harbin biochemistry institute) additionally. Evaluated thegrade before treatment and on the seventh and fourteenth day after treatmentrespectively according to Hughes scale, compared the effective time and thedecrease of the Hughes grade of the 2 groups by t test, then compared the validrate of the two groups by X2 test by PC.SPSS software. Change of MCV wasalso recorded and meliorating of dyspnea was observed particularly. The two groups had no significant difference in age, sex, course andHughes scale（P>0.05）before treatment。Patients with severe infection,tuberculosis, diabetes and other severe viscera dysfunction were excluded.Evaluated the curative effect by assessing the improving grade of Hughesscale: There was no statistic difference by Hughes scale beforetreatment(P>0.05) between two groups，but on the 7th day, 14th day and 21thday after treatment, there were significant difference (P<0.01,P<0.02respectively). Compared the course of improving 1 and 2 grades according toHughes scale of two groups, we found that the course of the combined group 41<WP=47>was significantly shorter than that of the DXM group (P<0.01). The valid rateof the combined group were slightly higher than that of the DXM group( 90.63% and 82.85% respectively)when evaluated on the 21th day (P>0.05).IVIG could alleviate dyspnea swiftly and could promote the recovery of MCV.The risk of onset of side effects was 8.57% for DXM group, 9.37% forcombined group. No severe side effects appeared during treatment. Conclusions: IVIG combined with GS on treating GBS excelled thatwhich using GS only on clinical effective time, on improving Hughes scaleand effective rate. IVIG combined更多还原