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资木瓜总苷对RA模型小鼠的骨保护作用及机制
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| 篇名： | 资木瓜总苷对RA模型小鼠的骨保护作用及机制 |
| TITLE： | The osteoprotective effects and mechanisms of RA model mice by total saponins of Chaenomeles speciosa |
| 摘要： | 目的 研究资木瓜总苷对类风湿关节炎（RA）模型小鼠的骨保护作用及可能机制，为进一步将其开发为抗RA药物提供参考。方法将70只雄性DBA/1小鼠按随机数字表法分为正常组、模型组、资木瓜总苷低剂量组（60mg/kg）、资木瓜总苷高剂量组（240mg/kg）和雷公藤多苷片组（阳性对照，30mg/kg），每组14只。除正常组外，其余各组小鼠均采用葡萄糖-6-磷酸异构酶混合多肽诱导制备RA小鼠模型。观察并记录各组小鼠的体质量、后足趾厚度、关节炎评分；采用苏木精-伊红染色法、抗酒石酸酸性磷酸酶染色法及番红固绿染色法观察小鼠踝关节组织的滑膜炎症及骨、软骨破坏情况；采用酶联免疫吸附测定法检测小鼠血清中白细胞介素6（IL-6）和踝关节组织中肿瘤坏死因子α（TNF-α）、IL-4、IL-10的含量；采用Westernblot法检测小鼠踝关节组织中核因子κB受体活化因子配体（RANKL）、核因子κB受体活化因子（RANK）、骨保护素（OPG）、肿瘤坏死因子受体相关蛋白6（TRAF6）、活化T细胞核因子1（NFATC1）的蛋白表达水平。结果在给药结束时，与正常组比较，模型组小鼠的体质量显著降低（P＜0.05），关节炎评分和左、右后足趾厚度均显著增加（P＜0.05）；踝关节组织出现明显滑膜增生和炎症细胞浸润，破骨细胞数目明显增多，软骨组织破坏明显；血清中IL-6含量及踝关节组织中TNF-α含量和RANKL、RANK、TRAF6、NFATC1蛋白表达水平均显著升高（P＜0.05），而踝关节组织中IL-4、IL-10含量和OPG蛋白表达水平均显著降低（P＜0.05）。与模型组比较，各给药组小鼠的上述病理形态学变化和指标含量/水平均得到显著改善（P＜0.05）。结论资木瓜总苷对RA模型小鼠具有一定的骨保护作用；其机制可能与降低IL-6、TNF-α含量，升高IL-4、IL-10含量，抑制RANKL/RANK/OPG信号通路活化，从而抑制破骨细胞增殖和促进软骨及骨组织修复有关。 |
| ABSTRACT： | OBJECTIVE To study the osteoprotective effects and possible mechanism of total saponins of Chaenomeles speciosa on rheumatoid arthritis （RA） model mice， and to provide reference for further development of anti-RA drugs. METHODS Seventy male DBA/1 mice were randomly divided into normal group， model group， low-dose and high-dose groups of C. speciose total saponins （60， 240 mg/kg）， Tripterygium wilfordii polyglycoside tablets group （positive control， 30 mg/kg）， with 14 mice in each group. In addition to the normal group， the other groups of mice were induced by glucose-6-phosphate isomerase mixed polypeptide to prepare RA model. The body weight， rear toes thickness and arthritis scores of each group were recorded； the synovial inflammation， bone and cartilage destruction of ankle joint tissues were observed by hematoxylin-eosin staining， tartrate- resistant acid phosphatase staining and safranin O-fast green staining； the contents of interleukin-6 （IL-6） in serum and tumor necrosis factor α （TNF-α）， IL-4 and IL-10 in ankle joint tissues were detected by ELISA； the expression levels of receptor activator of nuclear factor-κB ligand （RANKL）， receptor activator of nuclear factor-κB （RANK）， osteoprotegerin （OPG）， tumor necrosis factor receptor-associated protein 6 （TRAF6） and nuclear factor of activated T cells 1 （NFATC1） protein in ankle joint tissues were detected by Western blot assay. RESULTS At the end of administration， compared with normal group， the body mass of mice in the model group was significantly reduced （P＜0.05）， and the arthritis score and the thickness of the left and right rear toes were significantly increased （P＜0.05）； the ankle joint tissues of mice in the model group showed significant synovial proliferation and inflammatory infiltration， the number of osteoclasts increased significantly and significant destruction of cartilage tissue. The content of IL-6 in serum， the content of TNF-α， the protein expression levels of RANKL， RANK， TRAF6 and NFATC1 in the ankle joint tissues were increased significantly （P＜0.05）， while the contents of IL- 4 and IL-10， the protein expression level of OPG in the ankle joint tissues were decreased significantly （P＜0.05）. Compared with model group， above pathomorphological changes and the content/level of indicators of mice in each administration group were significantly improved （P＜0.05）. CONCLUSIONS Total saponins of C. speciosa may exert osteoprotective effects on RA model mice， the mechanism of which may be associated with reducing the contents of IL-6 and TNF-α， increasing the contents of IL-4 and IL-10， inhibiting the activation of RANKL/RANK/OPG signal pathway， thus inhibiting the proliferation of osteoclasts and promoting the repair of cartilage and bone tissue. |
| 期刊： | 2023年第34卷第09期 |
| 作者： | 邓颖；金璨；段志豪；张晓丽；李世刚 |
| AUTHORS： | DENG Ying，JIN Can，DUAN Zhihao，ZHANG Xiaoli，LI Shigang |
| 关键字： | 资木瓜总苷；类风湿关节炎；核因子κB受体活化因子配体；核因子κB受体活化因子；骨保护素 |
| KEYWORDS： | total saponins of Chaenomeles speciosa； rheumatoid arthritis； receptor activator of nuclear factor- κB ligand； |
| 阅读数： | 166 次 |
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