双膦酸盐及其联合甲氨蝶呤对CIA大鼠炎症与骨破坏影响的研究

发布时间：2018-03-27 12:41

本文选题：胶原诱导性关节炎　切入点：双膦酸盐　出处：《中国骨质疏松杂志》2017年04期

【摘要】：目的建立模拟类风湿关节炎(rheumatoid arthritis,RA)发病的胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠模型,探讨双膦酸盐(bisphosphonate,BP)及双膦酸盐联合甲氨蝶呤(methotrexate,MTX)、自拟补肾强骨方对CIA大鼠关节炎症及局部骨破坏的作用及机制,为临床提供实验依据。方法建立CIA大鼠模型,将大鼠随机分为5组:(1)灭菌用水治疗(8只);(2)BP+自拟补肾强骨方治疗组(8只);(3)BP+MTX治疗组(8只);(4)BP治疗组(8只);(5)恩利+MTX治疗组(8只)。每只大鼠均在炎症分值达到2分及以上时开始治疗,从治疗开始隔天进行关节炎症评分,绘出炎症变化曲线,评价各治疗方法对炎症的抑制作用;治疗4w后,处死大鼠,左侧股骨和第5腰椎行骨生物力学检查,胫骨上段行micro-CT扫描和制作硬组织切片,观察股骨及腰椎的骨生物力学的变化,胫骨上段骨小梁变化及骨量变化。结果 BP+自拟补肾强骨方组和BP+MTX组对CIA大鼠关节炎症均具有明显抑制作用,二组比较差异无统计学意义。BP+自拟补肾强骨方、BP+MTX组和恩利+MTX组均具有明显的抑制CIA大鼠炎症关节周围骨量丢失的能力,且BP+自拟补肾强骨方、BP+MTX组抑制骨量减少的作用主要是通过抑制骨小梁数量减少及增加骨小梁宽度来实现的。而在骨生物力学检查中,BP+自拟补肾强骨方与MTX+恩利组对于皮质骨和松质骨强度的改善明显。而BP组则对于皮质骨强度和松质骨强度均无明显改善作用。因此BP联合自拟补肾强骨方与BP联合MTX对于促进骨小梁数量的增殖有较好的作用,改善皮质骨和松质骨的强度,效果较单独使用BP好。结论 BP联合MTX或自拟补肾强骨方均能明显抑制CIA大鼠关节炎症反应、关节侵蚀及关节周围骨丢失的作用。
[Abstract]:Objective to establish a collagen-induced arthritis-induced rat model of rheumatoid arthritis (RA). To investigate the effect and mechanism of bisphosphonate bisphosphonate (bisphosphonate) and methotrexate methotrexate (MTX) combined with methotrexate methotrexate (MTX) on arthritis and local bone destruction in CIA rats, and to provide experimental basis for clinical application. Methods CIA rat model was established. The rats were randomly divided into 5 groups: 1) 8 rats were treated with sterilizing water, 8 rats in the treatment group were treated with Bushen Qianggu prescription, 8 rats in the MTX treatment group were divided into 8 rats in the control group and 8 rats in the control group (n = 8), 8 rats in the treatment group treated with Enli MTX, and 8 rats in each group. The inflammatory score of each rat was up to 2 points and 8 rats in the treatment group. When treatment began above, After 4 weeks of treatment, the rats were killed, the left femur and the fifth lumbar vertebrae were examined by bone biomechanics. The bone biomechanics of femur and lumbar vertebrae were observed by micro-CT scanning and hard tissue section. Results both BP self-made Bushen Qianggu prescription group and BP MTX group had obvious inhibitory effects on arthritis of CIA rats. There was no significant difference between the two groups. BP self-made Bushen Qianggu prescription BP MTX group and Enli MTX group both had the ability to inhibit the loss of bone mass around the inflammatory joint in CIA rats. The effect of BP self-made Bushen Qianggu prescription (BP MTX) on inhibiting the decrease of bone mass was mainly achieved by inhibiting the reduction of bone trabecular number and increasing the width of bone trabecula. In bone biomechanical examination, BP self-made Bushen Qianggu Fang and MTX Enri. The cortical bone strength and cancellous bone strength were significantly improved in the BP group, while the cortical bone strength and the cancellous bone strength were not improved in the BP group. Therefore, the combination of BP and BP combined with Bushen Qianggu recipe and BP combined with MTX could promote the number of trabecular bone. Has a good effect on proliferation, Conclusion BP combined with MTX or self-made prescription of Bushen Qianggu can significantly inhibit arthritis reaction, joint erosion and bone loss around joints in CIA rats.
【作者单位】：上海市光华中西医结合医院;
【基金】：上海市科学技术委员会资助项目(134119b1500) 上海市长宁区科学技术委员会资助项目(CNKW2014J0S)
【分类号】：R593.22

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