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基于AMPK/mTOR信号通路研究膝痹宁方对膝骨关节炎模型大鼠的改善作用机制
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| 篇名： | 基于AMPK/mTOR信号通路研究膝痹宁方对膝骨关节炎模型大鼠的改善作用机制 |
| TITLE： | Study on improvement effect mechanism of Xibining prescription on knee osteoarthritis model rats based on AMPK/mTOR signaling pathway |
| 摘要： | 目的 基于腺苷酸活化蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路探究膝痹宁方（XBN）对膝骨关节炎（KOA）模型大鼠的改善作用机制。方法将36只大鼠随机分为空白组、模型组、XBN组（12.56g/kg）、XBN+二甲双胍（AMPK激动剂）组[12.56g/kgXBN+100mg/kg二甲双胍]，每组9只。除空白组外，其余各组大鼠均通过离断前交叉韧带的方法复制KOA模型。造模成功后，各组大鼠给予相应药物/生理盐水，XBN和生理盐水每天灌胃1次，二甲双胍隔天腹腔注射1次，连续4周。观察大鼠软骨组织病理形态学变化并进行Mankin评分，检测大鼠软骨组织中聚集蛋白聚糖（Aggrecan）的表达水平，血小板反应蛋白解整合素金属肽酶4（ADAMTS-4）、ADAMTS-5、基质金属蛋白酶3（MMP-3）、MMP-13的mRNA和蛋白表达水平，及AMPK、mTOR蛋白的磷酸化水平。结果与空白组比较，模型组大鼠软骨组织结构分层紊乱，软骨层基质淡染，潮线出现扭曲或中断，Mankin评分显著升高（P＜0.05）；软骨组织中Aggrecan蛋白表达水平和AMPK蛋白的磷酸化水平均显著降低（P＜0.05），ADAMTS-4、ADAMTS-5、MMP-3、MMP-13mRNA和蛋白的表达水平以及mTOR蛋白的磷酸化水平均显著升高（P＜0.05）。与模型组比较，各给药组大鼠软骨病理形态学变化明显改善，上述评分或指标水平均显著逆转（P＜0.05）。与XBN组比较，XBN+二甲双胍组大鼠软骨病变程度进一步减轻，上述评分或指标水平进一步改善（P＜0.05）。结论XBN可改善KOA模型大鼠的软骨损伤，促进软骨合成，减少软骨降解，其作用机制可能与激活AMPK/mTOR信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the improvement effect mechanism of Xibining prescription （XBN） on knee osteoarthritis （KOA） model rats based on AMP-activated protein kinase（AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Totally 36 rats were randomly divided into blank group， model group， XBN group （12.56 g/kg）， XBN+metformin （AMPK agonist） group （12.56 g/kg XBN+100 mg/kg metformin）， with 9 rats in each group. Except for blank group， KOA model was induced by anterior cruciate ligament transection in other groups. After modeling， each group was given relevant medicine/normal saline， XBN and normal saline intragastrically， once a day， and metformin intraperitoneally， every other day， for 4 consecutive weeks. The pathomorphological changes of cartilage tissue in rats were observed and Mankin scoring was conducted. The expression level of Aggrecan in rat cartilage， mRNA and protein expressions of platelet reactive protein disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS-4）， ADAMTS-5， matrix metalloproteinase 3 （MMP-3） and MMP- 13， and the phosphorylation level of AMPK and mTOR proteins were detected. RESULTS Compared with blank group， the structure of cartilage tissue in the model group was disordered， the matrix of cartilage layer was lightly stained，the tide line was distorted or interrupted， and Mankin score was significantly increased （P＜0.05）. The protein expression of Aggrecan in cartilage tissue and the phosphorylation level of AMPK protein were all decreased significantly （P＜0.05）； mRNA and protein expressions of ADAMTS-4， ADAMTS-5， MMP-3 and MMP-13 and the phosphorylation levels of mTOR protein were significantly increased in cartilage tissues （P＜0.05）. Compared with model group， the pathological morphology of cartilage was improved significantly in each administration group， and above score or indexes were reversed significantly （P＜0.05）. Compared with XBN group， the degree of cartilage lesions in rats was further alleviated in XBN+ metformin group， and the levels of above score or indicators were further improved （P＜0.05）. CONCLUSIONS XBN can ameliorate cartilage injury in KOA model rats， promote cartilage synthesis and reduce cartilage degradation， the mechanism of which may be associated with activating AMPK/mTOR signaling pathway. |
| 期刊： | 2023年第34卷第01期 |
| 作者： | 廖太阳；张力；杨楠；魏义保；吕璟先；徐波；丁亮；王培民；张立 |
| AUTHORS： | LIAO Taiyang， ZHANG Li，YANG Nan，WEI Yibao，LYU Jingxian，XU Bo，DING Liang，WANG Peimin，ZHANG Li |
| 关键字： | 膝痹宁方；膝骨关节炎；腺苷酸活化蛋白激酶；哺乳动物雷帕霉素靶蛋白；软骨 |
| KEYWORDS： | Xibining prescription； knee osteoarthritis； AMP-activated protein kinase； mammalian target of rapamycin； cartilage |
| 阅读数： | 220 次 |
| 本月下载数： | 8 次 |
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