TNF-α拮抗剂对胶原诱导大鼠类风湿关节炎骨破坏治疗作用的实验研究

Experimental study of the therapeutic effect of TNF-α antagonist on bone destruction in CIA rats

目的建立模拟类风湿关节炎(RA)发病的CIA大鼠模型,明确TNF-α拮抗剂对CIA大鼠关节局部骨破坏的改善作用,为临床提供实验依据。方法利用皮下注射牛II型胶原诱导Wistar大鼠发病,建立CIA大鼠模型。将大鼠随机分为3组:①正常对照组(10只);②灭菌用水治疗组(10只);③TNF-α拮抗剂治疗组(10只)。每只大鼠均在炎症分值达到两分及以上时开始治疗,分别在治疗4周和8周后,取胫骨上段做硬组织切片,观察胫骨上段骨小梁变化及骨量变化情况。结果 TNF-α拮抗剂具有明显抑制CIA大鼠关节周围骨量丢失的作用,且其抑制骨量减少主要是通过抑制骨小梁数量减少来实现的,与抑制骨小梁宽度丢失关系较小。结论 TNF-α拮抗剂能明显抑制CIA大鼠关节侵蚀及关节周围骨丢失。

Objective To establish CIA rat model, to confirm the potential curative effect of TNF-α antagonist on bone destruction, and to provide experimental evidence for clinical use. Methods CIA rat model was established by injecting bovine type Ⅱ collagen into Wistar rats subcutaneously. All the rats were randomly divided into 3 groups： normal control group （ n = 10） , sterilized water treatment group （ n = 10） , and TNF-α antagonist treatment group （ n = 10）. Each rat received treatment while the inflammation score reached to 2 points or above. After the treatment for 4 weeks or 8weeks, the rats were killed, and the proximal tibia was collected for hard-tissue slices. The changes of bone trabeculae and bone mass were observed. Results TNF-αantagonist could obviously inhibit periarticular bone loss in CIA rats. The effect mainly depended on the inhibition of the loss of bone trabecular number, but not the loss of trabecular width. Conclusion TNF- αantagonist can obviously inhibit joint erosion and periarticular bone loss in CIA rats.