目的 通过观察藤莓汤(Tengmei Decoction,TMD)对胶原诱导性(collagen-induced arthritis,CIA)大鼠滑膜中突变型P53(Mutant P53,mt-p53)、增殖诱导配体(a proliferation-inducing ligand,APRIL)，白细胞介素2(Lnterleukin 2,IL-2)表达的影响，探讨藤莓汤抑制类风湿关节炎(rheumatoid arthritis,RA)滑膜免疫炎性损伤的分子机制。方法 建立CIA大鼠模型，中药给药组分为TMD高剂量组、TMD低剂量组，分别以TMD生药量31.8、15.9 g/(kg·d^-1)灌胃；模型组、阳性对照组分别予去离子水10 mL/(kg·d^-1)、来氟米特1.87 mg/(kg^-1·d^-1)灌胃；另设正常对照组，予去离子水10 mL/(kg·d^-1)，各组连续干预12周。干预结束后检测mt-P53、APRIL、IL-2蛋白及mRNA表达。结果 与正常组比较，模型组APRIL、mt-P53、IL-2 mRNA转录水平上调(P < 0.01)；mt-P53、IL-2蛋白表达上调(P < 0.01，P < 0.05)。与模型组比较，各治疗组APRIL mRNA转录水平，mt-P53、IL-2mRNA转录水平及蛋白表达水平下调，(P < 0.01，P < 0.05)；结论 TMD能够降低大鼠关节滑膜、血清中mt-P53、IL-2、APRIL表达水平，改善关节炎模型大鼠关节滑膜免疫炎性损伤，可能与TMD抑制关节滑膜过度增殖，降低炎症因子的表达有关。

Objective To observe the effects of Tengmei Decoction (TMD) on mutant P53 (mt-p53), proliferation-inducing ligand (APRIL) and interleukin-2 (IL-2) expression in synovium of collagen-induced arthritis (CIA) rats, and to explore its inhibitory effect on rheumatoid arthritis (RA) synovitis immunity. Molecular mechanism of sexual injury.Methods CIA rat model was established. The rats were randomly divided into model group, positive control group, high dose TMD group and low dose TMD group. Normal control group was set up with 6 rats in each group. The normal control group and model group were given deionized water 10 mL/(kg-1 d-1) by gastric lavage, the positive drug group was given leflunomide 1.87 mg/(kg-1 d-1) by gastric lavage, and the TMD high and low dose groups were given TMD 31.8 and 15.9 g/(kg-1 d-1) by gastric lavage respectively for 12 weeks. After the intervention, the expression of mt-P53, APRIL, IL-2 protein and mRNA were detected.Results Compared with the normal group, the transcriptional levels of APRIL, mt-P53 and IL-2 were up-regulated in the model group (P < 0.01), and the expressions of mt-P53 and IL-2 were up-regulated (P < 0.01, P < 0.05). Compared with model group, APRIL transcription level, mt-P53, IL-2 transcription level and protein expression level in each treatment group were down-regulated (P < 0.01, P < 0.05).Conclusion TMD can reduce the expression of mt-P53, IL-2 and APRIL in synovium and serum of rats, and improve the immune inflammatory injury of synovium in arthritis model rats, which may be related to TMD inhibiting synovium proliferation and reducing the expression of inflammatory factors.

国家自然科学基金面上项目（51772032）：虎杖苷RGD三肽/叶酸双靶向MSNs载药系统的构建及其抑制RA免疫炎性代谢性损伤的应用基础研究；负责人：孟凤仙;北京中医药大学基本科研业务费在读研究生项目（2018-JYB-XS218）：藤莓汤对Ⅱ型胶原诱导性大鼠滑膜mt-p53/Tgif2/NF-κB介导骨细胞代谢紊乱的机制研究；负责人：杨蕾。