摘要
目的:研究资木瓜总苷(TSCS)通过MC-Tryptase-PAR-2-FLS途径对K/B×N小鼠血清转移性关节炎的治疗作用。方法:小鼠随机分为6组:C57BL/6小鼠分别注射C57BL/6小鼠血清、K/B×N小鼠血清作为正常对照组和模型组,KitW-4Bao小鼠注射K/B×N小鼠血清作为阴性对照组,移植肥大细胞(MC)的KitW-4Bao小鼠随机分为3组:阳性药物(色甘酸钠)组、TSCS低、高剂量组,均注射K/B×N小鼠血清。游标卡尺测量小鼠关节肿胀度,HE染色观察关节形态学变化,甲苯胺蓝染色观察MC脱颗粒变化,免疫组化和qRT-PCR检测关节组织中类胰蛋白酶(Tryptase)、蛋白酶激活受体2(PAR-2)表达情况,ELISA检测血清IgG及关节中炎症因子含量变化。结果:KitW-4Bao小鼠对血清转移性关节炎抵抗,移植MC后,对K/B×N小鼠血清恢复敏感,引发关节炎。与模型组相比,TSCS高剂量组小鼠关节肿胀度、关节炎评分、病理学评分、MC脱颗粒率、Tryptase和PAR-2表达、血清IgG和炎症因子水平显著降低。结论:MC在K/B×N小鼠血清转移性关节炎模型中发挥重要作用;TSCS通过抑制MC脱颗粒释放类胰蛋白酶,影响MC-Tryptase-PAR-2-FLS通路,治疗K/B×N小鼠血清转移性关节炎。
Objective:To investigate therapeutic effect of TSCS based on MC-Tryptase-PAR-2-FLS pathway on K/B×N serumtransfer arthritis.Methods:Mice were divided into 6 groups randomly:C57 BL/6 mice were injected with C57 BL/6 mouse serum and K/B×N mouse serum as normal control group and model group,KitW-4Baomice were injected with K/B×N mouse serum as negative control group,KitW-4Baomice transplanted with mast cells(MC)that injected with K/B×N mouse serum were divided into 3 groups:cromolyn group,TSCS low-dose group and high-dose group.Vernier caliper was used to measure degree of joint swelling,morphological changes of joints were observed by HE staining,change of degranulation of MC was observed by toluidine blue staining,expressions of Tryptase and PAR-2 in joint tissues were detected by immunohistochemistry and qRT-PCR,and ELISA was used to detect changes of levels of serum IgG and inflammatory factors in joints.Results:KitW-4Baomice were resistant to serum-transfer arthritis.KitW-4Baomice transplanted with MC were sensitive to K/B×N mouse serum and produced arthritis.Compared with model group,joint swelling degree,arthritis score,pathology score,MC degranulation rate,Tryptase and PAR-2 expressions,serum IgG and tissue inflammatory factors levels in high-dose of TSCS group were significantly decreased.Conclusion:MC play an important role in K/B×N serum-transfer arthritis model.TSCS can inhibit Tryptase released from MC,affecting MC-Tryptase-PAR-2-FLS pathway and produced therapeutic effect on K/B×N serum-transfer arthritis.
作者
周婷婷
陈先勇
陈桂婷
曹楠
李世刚(指导)
ZHOU Ting-Ting;CHEN Xian-Yong;CHEN Gui-Ting;CAO Nan;LI Shi-Gang(Medical College of China Three Gorges University,Yichang 443002,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第4期395-399,409,共6页
Chinese Journal of Immunology
基金
国家自然科学基金项目(81673665,81274166)
湖北省卫生健康委员会联合基金重点项目(WJ2019H531)
