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| 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 |
| The experimental study of the efficacy of bisphosphonates in combination with methotrexate on inflammation and bone erosion in CIA rats |
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| DOI：10.3969/j.issn.1006.7108.2017.04.006 |
| 中文关键词: 胶原诱导性关节炎 双膦酸盐 炎症 骨破坏 类风湿性关节炎 |
| 英文关键词:Collagen-induced arthritis Bisphosphonate Inflammation Bone destruction Rheumatoid arthritis |
| 基金项目:上海市科学技术委员会资助项目（134119bl500);上海市长宁区科学技术委员会资助项目（CNKW2014J0S) |
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| 中文摘要: |
| 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）；②BP+自拟补肾强骨方治疗组（8只）；③BP + MTX治疗组（8只）；④BP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査，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。 |
| 英文摘要: |
| Objective Through establishing CIA rat model which imitates pathogenic factors of RA，we aimed to study the effects of BPs, BPs with MTX and BPs with Traditional Chinese Medicine in relieving joint inflammation and bone erosion. The results may provide experimental evidence for clinical application. Methods Firstly the CIA rat model was established, then the rats were randomly divided into five groups：①The sterilized water treatment group (n =8)；②The BPs + MTX treatment group (n =8)；③ The BPs + Bushen Qianggu drugs treatment group ( n = 8)；④The BPs treatment group (n = 8)；⑤The Etanercept + MTX treatment group ( n = 8). Each rat began to receive treatment when inflammation scores reached two points or above. From the beginning of treatment, we scored arthritis and wrote it onto score table, draw the variation curve of inflammation scores, and evaluated the effect of each treatment method for the inhibition of inflammation. After treatment of 4 weeks, we killed the rats, took the left femur and fifth lumbar vertebrae to have bone biomechanical check, scanned proximal tibia using micro-CT, made hard- tissue slices, and then observed the changes in bone biomechanics at femur and lumbar spine of each group, and evaluated trabecular variation and bone quantity changes of proximal tibia of each group. Results The results showed that the BPs + MTX and BPs + Bushen Qianggu drug treatment had obvious inhibitory effect on the joint inflammation of CIA rats(P <0. 05). All treatment groups except BPS group had obvious inhibition on the periarticular bone loss of CIA rat( P <0. 05). The ability was mainly dependent on the inhibition on the loss of trabecular bone number, and on the increase of trabecular width ( P < 0.05 ). In the Bone Biomechanical Examination，the BPs + Bushen Qianggu drug and Etannercpt + MTX groups had significantly improved strength of the cortical bone and cancellous bone. The BPs drug had no significant effect on improving the strength of cancellous bone and cortical bone. Conclusion The BPs + Bushen Qianggu drug and BPs + MTX had obvious inhibition effects on joint inflammatory reaction, joint erosion and periarticular bone loss of CIA rats. |
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