芬戈莫德对小鼠类风湿关节炎骨质疏松模型的辅助性T细胞17／核因子κB受体活化因子配体／骨保护素骨免疫机制研究  

Effect of FTY720 on the osteoimmune mechanism of T helper 17/receptor activator of nuclear factor Kb ligand/osteoproteger in in collagen - induced arthritis mice

作　　者：寿志强[1] 严楷蕾 李慧辉 黄胜[1] 高宏梁[1] 刘俊华[1] 寿旗扬[2] 蒋雪生[1] Shou Zhiqiang;Yan Kailei;Li Huihui;Huang Sheng;Gao Hongliang;Liu Junhua;Shou Qiyang;Jiang Xuesheng(Department of Orthopedics, Huzhou Central Hospital, Huzhou 313003, China;Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Chin;Department of Orthopedics and Traumatology of TCM, Ruian People＇ s Hospital, Ruian 325200, China)

机构地区：[1]浙江省湖州市中心医院骨科,313003 [2]浙江中医药大学比较医学研究所,杭州310053 [3]浙江省瑞安人民医院中医骨伤科,325200

出　　处：《中华实验外科杂志》2018年第6期1122-1125,共4页Chinese Journal of Experimental Surgery

基　　金：浙江省公益性技术应用研究计划（2017C37151、2017C37119）;浙江省医药卫生科技计划（2015KYA211）

摘　　要：目的探讨芬戈莫德对小鼠类风湿关节炎（RA）骨质疏松模型的辅助性T细胞17（Thl7）／骨保护素（OPG）／核因子KB受体活化因子配体（RANKL）骨免疫机制。方法RA造模10周后进行分组，小鼠每天口服0．25、0．50、1．00mg／kg芬戈莫德，连续给药8周，观察小鼠血清白细胞介素（IL）-17、OPG水平、脾脏IL-17、维甲酸相关孤核受体γt（ROR-γt）、活化T细胞核因子（NFAT）、又状头／翅膀状螺旋转录因子（Foxp3）及骨OPG、RANKLmRNA的变化。结果小鼠造模后，小鼠血清IL-17水平从（8．07±0．98）pg／ml升高至（32．08±6．09）pg／ml（P=0．007），给予FTY720后，高、中剂量组小鼠血清IL-17水平明显降低至（11．49±3．07）pg／ml和（11．49±3．07）pg／ml（分别为P=0．009、0．048）；FTY720高剂量组小鼠脾脏中NFAT、ILl7、ROR-γtmRNA水平显著明显降低（分别为JP=0．000、0．009、0．001），同时可显著升高FOXP3mRNA水平（P=0．010）；FTY720高、中剂量组小鼠血清OPG水平明显升高（分别为P=0．019、0．007）。FTY720高、中、低剂量组小鼠股骨中OPGmRNA水平明显升高（P=0．000），而高、中剂量组小鼠RANKLmRNA水平明显降低（分别为P=0．049、0．040）。结论FTY720通过抑制Thl7细胞和提高调节性T细胞功能来降低IL-17的分泌．影响OPG／RANKL水平。Objective To observe the effect of FTY720 on the osteoimmune mechanism of T helper 17 （Thl7）/receptor activator of nuclear factor κb ligand （RANKL）/osteoprotegerin （OPG） in type 2 collagen - induced arthritis mice. Methods Ten weeks after establishment of type 2 collagen - induced rheumatoid arthritis （RA） osteoporosis model in mice, the animals were grouped. Mice were administrated by 0. 25, 0. 5, 1.0 mg/kg FTY720 for 8 weeks respectively. Serum interleukin （IL） - 17, OPG, splenic IL - 17, receptor - γt （ ROR - γt）, nuclear factor of activated T cell （ NFAT）, forkhead/winged helix transcription factor P3 （ Foxp3 ） and bone RANKL mRNA were observed in RA osteoporosis mice. Results After model establishment in mice, the serum IL - 17 level increased from （ 8.07 ± 0. 98 ） pg/ml to （ 32. 08± 6. 09 ） pg/ml in mice. After oral administration of FTY720, serum IL - 17 levels in the high and medium dose groups were significantly reduced to （ 11.49 ± 3.07 ） pg/ml and （ 11.49 ± 3.07 ） pg/ml （P =0. 009, P = 0. 048 respectively）. The levels of NFAT, IL - 17, ROR - γt mRNA in spleen of FTY720 high dose group were significantly decreased （ P = 0. 000, P = 0. 009, P = 0. 001 respectively ） , meanwhile the level of FOXP3 mRNA was significantly increased （P = 0. 010 ）. The serum OPG levels in FTY720 high and medium dose groups were significantly increased （P = 0. 019, P = 0. 007 respectively）. The levels of OPG mRNA in the femur of FTY720 high, medium and low dose groups were significantly in- creased （P = 0. 000）. The RANKL mRNA levels in the high and medium dose groups were significantly lower （P = 0. 049, P = 0. 040 respectively）. Conclusion FTY720 can reduce the secretion of IL - 17 by inhibiting Thl7 cells and enhancing the regulatory T cell function, then affecting the levels of OPG/RANKL. and effectivelv inhibitin~ the incidence of osteo^orosis in RA mice.

关 键 词：芬戈莫德 骨质疏松 辅助性T细胞17/核因子κB受体活化因子配体/骨保护素 

分 类 号：R-332[医药卫生] R965