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作者	单位	E-mail
唐华燕	上海中医药大学附属市中医医院风湿科上海 200071	doctanghuayan@163.com
徐星宇	上海中医药大学附属市中医医院风湿科上海 200071
张　娜	上海中医药大学附属市中医医院风湿科上海 200071
顾明珠	上海中医药大学附属市中医医院风湿科上海 200071
王不易	上海中医药大学附属市中医医院风湿科上海 200071

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中文摘要:

摘要目的：研究羌活地黄汤对佐剂性类风湿关节炎（RA）大鼠辅助性T细胞/调节性T细胞（Th17/Treg）失衡、血清基质金属蛋白酶-3（MMP-3）、基质金属蛋白酶-13（MMP-13）以及滑膜组织血管内皮生长因子（VEGF）、核因子-κB受体活化因子配基（RANKL） mRNA表达的影响。方法：取40只SD级大鼠进行研究，将其以随机数字表法分为正常对照组、模型组、羌活地黄汤组以及甲氨蝶呤组，每组各10只。除正常对照组外，其余各组大鼠均建立佐剂性RA动物模型。羌活地黄汤组予以羌活地黄汤灌胃干预，甲氨蝶呤组予以甲氨蝶呤灌胃干预，正常对照组及模型组均予以等量生理盐水灌胃干预。各组均进行为期28d的干预，比较各组体重、关节炎指数及关节肿胀度、外周血Th17/Treg相关指标、血清MMP-3、MMP-13水平、滑膜组织VEGF、RANKL mRNA表达。结果：模型组体重低于正常对照组，羌活地黄汤组、甲氨蝶呤组关节炎指数及关节肿胀度均低于模型组，而体重高于模型组（均P＜0.05）。模型组、羌活地黄汤组、甲氨蝶呤组的外周血CD4+IL-17+T、Th17/Treg均高于正常对照组，而Foxp3+CD4+CD25+Treg低于正常对照组，且羌活地黄汤组、甲氨蝶呤组的外周血CD4+IL-17+T、Th17/Treg均低于模型组，而Foxp3+CD4+CD25+Treg高于模型组（均P＜0.05）。模型组、羌活地黄汤组、甲氨蝶呤组的血清MMP-3、MMP-13水平均高于正常对照组，而羌活地黄汤组、甲氨蝶呤组的血清MMP-3、MMP-13水平均低于模型组（均P＜0.05）。模型组、羌活地黄汤组、甲氨蝶呤组的滑膜组织VEGF、RANKL mRNA表达水平均高于正常对照组，而羌活地黄汤组、甲氨蝶呤组的滑膜组织VEGF、RANKL mRNA表达水平均低于模型组（均P＜0.05）。结论：羌活地黄汤可改善佐剂性RA大鼠的症状以及Th17/Treg失衡状态，且有效改善其血清MMP-3、MMP-13水平以及滑膜组织VEGF、RANKL mRNA表达。

英文摘要:

ABSTRACT Objective: To study the effects of Qianghuo Dihuang decoction on helper T cells/regulatory T cells (Th17/Treg) imbalance, serum matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-13) and vascular endothelial growth factor (VEGF), receptor activator of nuclear factor-κB ligand (RANKL) mRNA expression in synovium tissue of adjuvant rheumatoid arthritis (RA) rats. Methods: 40 SD rats were taken for study, they were randomly divided into normal control group, model group, Qianghuo Dihuang decoction group and methotrexate group by random number table, with 10 rats in each group. Except for normal control group, adjuvant RA animal model was established in other groups. The Qianghuo Dihuang decoction group was given gavage intervention of Qianghuo Dihuang decoction, methotrexate group was given gavage intervention of methotrexate, normal control group and model group were given gavage intervention of normal saline. Each group was intervened for 28 days, the body weight, arthritis index, joint swelling degree, peripheral blood Th17/Treg related indicators, serum MMP-3 and MMP-13 levels, VEGF and RANKL mRNA expressions in synovial tissues were compared among all groups. Results: Body weight in model group was lower than that in normal control group, arthritis index and joint swelling degree in Qianghuo Dihuang decoction group and methotrexate group were lower than those in model group, but body weight was higher than that in model group (all P＜0.05). The peripheral blood CD4+IL-17+T and Th17/Treg in model group, Qianghuo Dihuang decoction group and methotrexate group were higher than those in normal control group, while Foxp3+CD4+CD25+Treg were lower than that in normal control group. The peripheral blood CD4+IL-17+T and Th17/Treg in Qianghuo Dihuang decoction group and methotrexate group were lower than those in model group, while Foxp3+CD4+CD25+Treg were higher than that in model group (all P<0.05). The serum MMP-3 and MMP-13 levels in model group, Qianghuo Dihuang decoction group and methotrexate group were all higher than those in normal control group, while the serum MMP-3 and MMP-13 levels in Qianghuo Dihuang decoction group and methotrexate group were lower than those in model group (all P<0.05). The VEGF and RANKL mRNA expression levels in synovium in model group, Qianghuo Dihuang decoction group and methotrexate group were higher than those in normal control group, while the VEGF and RANKL mRNA expression levels in synovium in Qianghuo Dihuang decoction group and methotrexate group were lower than those in model group (all P<0.05). Conclusion: Qianghudihuang Decoction can improve the clinical symptoms and Th17/Treg imbalance of adjuvant RA rats, and effectively improve the levels of MMP-3 and MMP-13 in serum, as well as the expressions of VEGF and RANKL mRNA in synovial tissues.

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