调控Gal-9/Tim-3通路对小鼠胶原诱导性关节炎作用的研究  

Effects of regulation of Gal-9/Tim-3 pathway on murine collagen-induced arthritis

作　　者：杨骁[1] 彭昊[1] 周建林[1] 方洪松[1] 陈森[1] 

机构地区：[1]武汉大学人民医院骨科,湖北武汉430000

出　　处：《中国医药导报》2016年第4期4-7,共4页China Medical Herald

基　　金：国家自然科学基金资助项目(81301592)

摘　　要：目的探讨激活或阻断Gal-9/Tim-3信号通路对小鼠胶原诱导性关节炎的影响及其机制。方法 6～8周龄雌性BALB/c小鼠30只,建立Ⅱ型胶原诱导性关节炎模型,造模后第7天加强免疫。于加强免疫前1 d随机分为激活组、阻断组、对照组,每组10只,分别经尾静脉输注半乳糖凝集素-9（Gal-9）、阻断剂Tim-3单抗、PBS。造模后28d观察三组小鼠踝关节变形程度,记录关节炎指数,ELISA法检测血清抗炎因子白介素-10（IL-10）、转化生长因子β（TGF-β）水平,RT-PCR检测踝关节滑膜组织辅助性T细胞（Th17）、调节性T细胞（Treg）标志性蛋白ROR-γt、Fox P3表达量。结果加强免疫后,三组小鼠出现不同程度关节变形,造模后第28天关节炎指数：激活组为（7.12±1.53）分、阻断组为（13.82±2.12）分、对照组为（10.88±1.84）分,差异有高度统计学意义（P〈0.01）;血清IL-10、TGF-β水平：激活组[（12.88±2.23）、（27.61±4.52）ng/L]明显高于对照组[（7.49±1.70）、（21.33±2.07）ng/L]（P〈0.01）,阻断组[（4.26±1.79）、（12.35±2.42）ng/L]明显低于对照组（P〈0.01）;RT-PCR结果显示：ROR-γt m RNA在滑膜组织的表达情况激活组明显低于对照组（P〈0.01）,阻断组明显高于对照组（P〈0.01）;Fox P3 m RNA表达情况激活组明显高于对照组（P〈0.01）,阻断组明显低于对照组（P〈0.01）。结论激活Gal-9/Tim-3通路可缓解小鼠胶原诱导性关节炎,阻断该通路则加重炎性反应,作用机制可能与该通路抑制Th17,活化Treg有关。Objective To explore the a11eviatory effects of Ga1-9/Tim-3 pathway on murine collagen-induced arthritis （CIA）. Methods Thirty SPF female BALB/c mice （age 6-8 weeks） were used in the study. Mice model of rheumatoid arthri- tis （RA） was established by subdermal injections of collagen Ⅱ, on the 7th day, strengthened immunity. The day before strengthened immunity, mice were randomly divided into three groups： activation group, control group and blockage group, with 10 mice in each group, transfusion through caudal vein was performed with Ga1-9, Tim-3 mAb and PBS respectively, 28 days after first immunization, the severity of CIA was evaluated with regards to arthritic index （AI）, ser- a levels of IL-10, TGF-β by ELISA, expressions of biomarkers of T helper 17 cells （Th17） and regulatory T cells （Treg） by RT-PCR. Results After second immunization, the ankle joints of CIA mice began to deform with mild to se- vere arthritis. On the 28th day after first immunization, the AI of activation group was （7.12±1.53） scores, control group was （10.88±1.84） scores, and AI of blockage group was （13.82±2.12） scores, the differences were statistically significant （P 〈 0.01）. Compared with control group, the sera concentrations of IL-10 and TGF-β of activation group were signifi- cantly higher （P 〈 0.01） while those of blockage group were significantly lower （P 〈 0.01）. The results of RT-PCR showed： the expression of ROR-γt in synovial tissue of activation group was lower than that of control group （P 〈 0.01）, and ROR-γt expression of blockage group was higher than that of control group （P 〈 0.01）; the expression of FoxP3 in synovial tissue of activation group was higher than control group （P 〈 0.01）, and FoxP3 of blockage group was lower than control group （P 〈 0.01）. Conclusion Murine CIA may be markedly ameliorated by acticvation of the Ga1-9/Tim- 3 pathway and exacerbated by blockage of it, possibly through the tunnel of inhibiting Th17, s

关 键 词：类风湿性关节炎 胶原诱导性关节炎 辅助性T细胞 调节性T细胞 信号通路 

分 类 号：R332[医药卫生—人体生理学]