目的 评价山茱萸水提液（CO）、0.05μm无机陶瓷膜微滤液（CO-0.05）及中空10 K纤维膜超滤液（CO-10K）对成纤维样滑膜细胞（HFLS）和佐剂性关节炎（AA）大鼠的抗炎作用，评价膜分离技术富集山茱萸抗炎组分的适用性。方法 制备白细胞介素-1β（IL-1β）/肿瘤坏死因子-α（TNF-α）诱导的HFLS炎症模型，CCK-8和ELISA法分别检测CO、CO-0.05及CO-10K对HFLS活力和分泌炎症细胞因子的影响；制备AA大鼠模型，SD大鼠分为对照组、模型组、CO（120 mg/kg）组、CO-0.05（120 mg/kg）组、CO-10K（120 mg/kg）组、阳性对照白芍总苷（TGP，0.125 mg/kg）组，造模同时ig给药，共给药23 d。检测各组大鼠足趾肿胀、体质量，ELISA法测定大鼠血清中炎症因子IL-1、IL-6、前列腺素E₂（PGE₂）、TNF-α水平。结果 CO、CO-0.05及CO-10K均可以显著抑制IL-1β/TNF-α诱导的滑膜细胞分泌细胞因子（P<0.05、0.01、0.001），并且能够显著缓解AA大鼠足趾肿胀（P<0.05、0.01、0.001），改善大鼠体质量增长缓慢的情况（P<0.05、0.01、0.001），减少AA大鼠血清中炎性细胞因子的产生（P<0.001）。通过山茱萸膜微滤液和膜超滤液对炎症细胞因子产生的抑制率比较，发现膜超滤液具有更显著的抑制炎症因子产生的作用。结论 CO-0.05和CO-10K均具有显著的抗炎作用，而中空纤维膜超滤分离技术更适用于山茱萸抗炎组分的富集。

Objective To investigate the anti-inflammatory effect of Cornus officinalis (CO) Decotion and its refined solutions from membrane separation by using 0.05 μm inorganic ceramic membrane (CO-0.05) and 10K polysulfone hollow fiber membrane (CO-10K), and evaluate the applicability of the membrane separation technique for concentrating the anti-inflammatory compounds of C. officinalis Decotion. Methods Inflammatory model of interleukin (IL)-1β and tumor necrosis factor (TNF)-α stimulated human fibroblast-like synoviocytes (HFLS) was prepared. The CCK-8 assay and ELISA were applied to detect the effects of C. officinalis Decotion and its refined solutions on the viability of HFLS and the secretion of inflammatory cytokines, respectively. Moreover, the animal model of adjuvant arthritis (AA) was used. The SD rats were divided into six groups:control group, model (AA) group and AA groups intragastrically receiving CO (120 mg/kg), CO-0.05 (120 mg/kg), CO-10K (120 mg/kg) and TGP (0.125 mg/kg) with daily treatments for 23 days. The weight and paw swelling of rats in different groups were detected. The ELISA was used to detect secretion levels of prostaglandin E₂ (PGE₂), IL-1, IL-6, and TNF-α in serum. Results The production of vascular endothelial growth factor (VEGF) induced by IL-1β/TNF-α were significantly inhibited with C. officinalis Decotion and its refined solutions by membrane separation treatment (P < 0.05, 0.01, 0.001). C. officinalis Decoction and the refined solutions significantly ameliorated paw swelling and increased weight gain of AA rats (P < 0.05, 0.01, 0.001), and reduced the secretion of TNF-α, PGE₂, IL-1, IL-6 in serum (P < 0.001). By comparing the inhibition efficiency of inflammatory cytokines by inorganic ceramic membrane refined solution and polysulfone hollow fiber membrane refined solution, the polysulfone hollow fiber membrane refined solution exhibited better anti-inflammatory activity. Conclusion Both of refined solutions of C. officinalis Decotion from inorganic ceramic membrane and polysulfone hollow fiber membrane separation exhibited dramatically anti-inflammtory activity. Moreover, the polysulfone hollow fiber membrane was more applicable for concentrating the anti-inflammatory compounds of C. officinalis Decotion.

国家自然科学基金资助项目（81773919）；陕西省科技厅重点研发项目一般项目（2017SF-364）；陕西省科技厅社发攻关课题（2015SF-246）；陕西省中药基础与新药研究重点实验室开放基金（2017KF06）