复方甘草酸苷对儿童过敏性紫癜Th17/Treg细胞免疫的影响

Effect of compound glycyrrhizin on Th17/Treg cells in children with Henoch-Schonlein purpura

摘要:

目的：探讨复方甘草酸苷（compound glycyrrhizin，GL）治疗儿童过敏性紫癜（Henoch-Schonlein purpura，HSP）的临床疗效，从Treg、Th17细胞及促炎因子方面探讨其免疫学机制。方法：27例初发HSP病人作为治疗组，26例作为疾病对照组，25例健康儿童作为正常对照组。治疗组在疾病对照组的基础上增加GL（0.5～2.0 ml/kg）静脉注射7 d治疗；留取治疗前后全血PBMC行流式检测Treg、Th17细胞阳性率，血浆ELISA法检测促炎因子TNF-α，干扰素诱导蛋白-10（interferon inducible protein-10，IP-10），白介素17（interleukin-17，IL-17），干扰素-γ（interferon-γ，IFN-γ）浓度变化。结果：①临床症状：治疗组皮疹消退时间较疾病对照组有缩短趋势，肾损害有缓解，1月内紫癜复发率低；②Treg、Th17细胞比例：治疗组治疗前Treg细胞阳性率低于正常对照组（P=0.010）；治疗后与正常对照组无统计学差异（P=0.059）；疾病对照组治疗后Treg低于治疗前及正常对照组（P=0.006，P=0.013）。治疗组治疗前Th17细胞阳性率高于治疗后及正常对照组水平（P=0.024，P=0.013）；治疗后Th17与正常对照组无统计学差异（P=0.337）。疾病对照组治疗前Th17亦明显高于治疗后水平（P=0.014）。③炎症因子：2组HSP治疗前血浆IL-17，IFN-γ浓度均高于正常对照组水平（P=0.013，P=0.010）；治疗组治疗后与正常对照组无统计学差异（P=0.052，P=0.154），疾病对照组两指标治疗前后比较无统计学差异（P=0.218，P=0.970）。治疗组治疗前血浆TNF-α、IP-10均高于治疗后（P=0.011，P=0.037），疾病对照组治疗前后2指标无统计学差异（P=0.247，P=0.709）。结论：①GL治疗儿童HSP，可减轻肾损害、短期内减少紫癜复发。②HSP患儿急性期，具有促炎作用的Th17和抗炎作用的Treg可能共同参与了其免疫发病。③GL具有下调Th17、上调Treg细胞比例，降低血浆IL-17、IFN-γ、TNF-α、IP-10水平的作用，提示GL可能具有一定T细胞免疫调节功能，在佐治儿童HSP免疫炎症方面有一定疗效。

Abstract:

Objective：To investigate the role of Th17/Treg and some cytokines imbalance in the pathogenesis of childhood Henoch-Schonlein purpura（HSP） and to further explore the clinical effectiveness and immunomodulatory effects of compound glycyrrhizin（GL） in HSP. Methods：Twenty-seven HSP patients were chose as GL-treated group，another 26 patients were used as conventional therapy group，and 25 age-and sex-matched healthy children were used as healthy controls. Intravenous injection of 0.5-2.0 ml/kg GL for 7 days was provided in GL-treated group on the basis of treatments in conventional therapy group. Blood samples of patients were ob－tained at the acute stage and after 7 days’ treatment.Postive cell rates of peripheral Th17 and Treg cells were detected by flow cytom－etry using intracellular staining. Serum levels of interleukin-17，interferon-γ，TNF-α，interferon inducible protein-10 were detected by ELISA. Results：①Clinical effectiveness：renal complications in GL-treated group were relieved and recurrence of HSP within 1 month was lower. ②Positive cell rate of Treg and Th17 cell：compared with that of healthy controls，the positive cell rate of Treg in GL-treated group was significantly down-regulated during acute phase（P=0.010） and was up-regulated after the treatment（P=0.059）. In conventional therapy group，positive cell rate of Treg was lower after the treatment compared with that before treatment and that of healthy control group（P=0.006，P=0.013）. The positive cell rate of Th17 in GL-treated group was significantly higher before the treat－ment compared with that after the treatment and that of conven－tional therapy group（P=0.024，P=0.013）. After the treatment，there was no difference in the positive cell rate of Th17 between GL-treated group and conventional therapy group（P=0.337）. The positive cell rate of Th17 in conventional therapy group was significantly higher before the treatment compared with that after the treatment（P=0.014）. ③Cytokines：Serum levels of IL-17 and IFN-γ were higher in GL-treated group and conventional therapy group than in healthy control group before the treatment（P=0.013，P=0.010）. There was no difference in serum levels of IL-17 and IFN-γ between GL-treated group after the treatment and healty control group（P=0.052，P=0.154）. There was no difference in serum levels of IL-17 and IFN-γ in conventional therapy group before and after the treatment（P=0.218，P=0.970）. Serum levels of TNF-α and IP-10 in GL-treated group were down-regulated after the treatment（P=0.011，P=0.037）. But no difference was detected in conventional therapy group before and after the treatment（P=0.247，P=0.709）. Conclusion：①GL could relieve the renal complications and decrease recurrence of HSP in a short period of time. ②Treg and Th17 might in part contribute to the process of HSP. ③GL could help to up-regulate Treg and down-regulate Th17，IL-17，IFN-γ，TNF-α，IP-10 level，thus regulating the Th17/Treg deviation and cytokine im－balance and alleviating cellular immunity in HSP.