地黄合剂在多发性硬化患者中抗炎性反应及调节免疫平衡机制探讨

Anti-inflammatory and immune-modulating effects of Dihuang Heji in the treatment of multiple sclerosis

目的观察地黄合剂（DHHJ）在多发性硬化（MS）患者中发挥的双向治疗作用并探讨其机制，方法将40例MS患者采用随机数字表法分为激素治疗组（n-20）与激素治疗＋DHHJ组（n=201，根据组名采取相应治疗.另设20例排除免疫系统疾病及感染类疾病的外科手术患者作为对照组、分别用ELISA法和流式细胞仪检测两组观察对象脑脊液（CSF）和外周血中胶质原纤维酸性蛋白（GFAP）和S100B的含量及CD4^＋细胞，CD8^＋细胞数目。用下肢功能状态的评分（Al）、延展残疾状态评分（EDSS）、上肢功能状态评分（9HPT）对MS患者进行临床评分并分析其与GFAP、S100B之间的关系。随访MS患者的复发情况。结果与对照组比较，MS组CSF中GFAP和S100B表达明显增强。差异有统计学意义（P〈0．05），并且与MS患者的AI、9HPT评分存在相关关系。DHHJ＋激素治疗组与激素治疗组患者CSF中GFAP和S100B含量差异也有统计学意义（P〈0．05），同时DHHJ＋激素治疗组MS的复发次数与激素治疗组比较芹异也有统计学意义（P〈0．05）。MS患者的外周血和CSF中出现CD4^＋细胞明显增多，CD8^＋细胞明显减少：CSF中更明显。给予不同的治疗后，CD4^＋细胞数目减少，CD8^＋细胞数目增多，DHHJ＋激素治疗组与激素治疗组之间差异有统计学意义（P〈0．05）。结论DHHJ一方面能够影响MS患者CSF中GFAP和S100B的表达，抑制胶质细胞的激活，达到抗炎性反应作用：另一方面DHHJ还可以通过上凋免疫抑制性CD8^＋细胞的数目，下调免疫辅助性CD4^＋细胞，发挥调节免疫平衡作用，最终达到双向治疗MS的作用，减少MS患者复发的次数。

Objective To observe the anti-inflammatory and immune-modulating effects of Dihuang Heji （DHHJ）, a compound traditional Chinese medicinal preparation, in patients with multiple sclerosis （MS） and explore the possible mechanisms underlying these effects. Methods Forty MS patients were randomized into prednisone treatment and prednisone＋DHHJ group for the corresponding treatments. Another 20 surgical patients without immune or inflammatory diseases undergoing lumbar anesthesia served as the control group. Glial fibrillary acidic protein （GFAP） and S100B levels in the cerebrospinal fluid （CSF） and the peripheral blood of these subjects were detected using enzyme-linked immunosorbent assay （ELISA）, and the numbers of CD4^＋ and CD8^＋ cells were detected by flow cytometry, The ambulation index （AI）, expanded disability status scale （EDSS） and 9-hole PEG test （9HPT） were used to assess the patients＇ clinical symptoms. All the patients were followed up for 3 years to record the number of times of MS relapse. Results GFAP and S100B levels in the CSF were significantly higher in the MS patients than in the healthy subjects, but lower in MS patients treated with prednisone plus DHHJ than in those with prednisone treatment only （P〈0.05）. In the MS patients, AI and 9HPT scores were correlated to the GFAP and S 100B levels in the CSF. Prednisone plus DHHJ treatmentwas associated with significantly reduced MS relapse in comparison with prednisone treatment alone （P〈0.05）. Before the treatment, the MS patients showed increased CD4^＋ cell number and decreased CD8^＋ cell number especially in the CSF; after the treatments, the CD4^＋ cells decreased and CD8^＋ cells increased, and this effect was stronger with prednisone plus DHHJ treatment （P〈0.05）. Conclusions DHHJ produces anti-inflammatory effect by inhibiting glial cell activation and modulating immune balance in MS, thus alleviating the symptoms of MS and reducing MS relapse. DHHJ may provide an ideal adjuvant therapy for MS.