DLTH通过调节免疫功能和软骨降解从而抑制RA的作用

目的以壳聚糖-甘油-硼砂为载体,制备新型的,可注射的,具有缓释作用的地塞米松温敏凝胶(dexamethasone-loaded thermosensitive hydrogel,DLTH)。观察DLTH对类风湿性关节炎(rheumatoid arthritis,RA)免疫调节和软骨保护作用。方法将30只大鼠分为对照组、模型组和DLTH组。对模型组和DLTH组构建RA模型。从d 12,DLTH组双侧膝关节内给药40μL DLTH(即1 mg·kg^-1地塞米松),每周两次,给药3周后取材。ELISA检测血清细胞因子IL-1β和TNF-α的表达,脾组织切片行HE染色,膝关节切片进行甲苯胺蓝染色和免疫组化分析,PCR检测相关炎症因子和降解酶变化。结果与模型组相比,DLTH组血清炎症因子及脾脏病理性变化明显减轻。DLTH可以显著抑制脾脏炎症因子表达和调整Th1/Th2、Th17/Treg失衡状态。同时,对软骨进行一系列分析发现,DLTH可以显著改善RA引起的软骨破坏现象,抑制软骨细胞中炎症因子和相关降解酶的表达。结论DLTH对RA具有明显的免疫调节和软骨保护作用。

Study of DLTH inhibiting RA byregulating immune function and cartilage degradation

Aim To observe the immune regulation and cartilage protection of dexamethasone-loaded thermosensitive hydrogel(DLTH)on rheumatoid arthritis(RA)rats via conceiving a newly injectable sustained DLTH with chitosan-glycerin-borax as carrier.Methods Thirty rats were randomly divided into three groups,namely control,model and DLTH group.RA model was established through immune induction in model and DLTH group.From the 12th day,rats of DLTH group were injected with 40μL DLTH(1 mg·kg^-1 dexamethasone)into both knee joints twice a week.Three weeks after administration,the rats were sacrificed.Serum levels of IL-1βand TNF-αin all rats were detected.Spleen tissue sections were stained with hematoxylin-eosin while knee tissue sections were stained with toluidine blue and immunohistochemistry.The cartilage changes in related inflammatory factors and degrading enzymes were detected by PCR.Results Compared with model group,the pathological changes of rat serum and spleen in DLTH group were significantly alleviated.DLTH could significantly inhibit the expression of inflammatory factors and adjust the imbalance of Th1/Th2 and Th17/Treg in spleen.Pathological analysis of cartilage showed that DLTH could significantly improve cartilage destruction and significantly inhibit the expression of inflammatory factors and related degradation enzymes in chondrocytes.Conclusion DLTH has obvious immune regulation and cartilage protection effect on RA.