多巴胺对骨关节炎的治疗作用及相关分子机制研究  

Study on Efficacy of Dopamine for Osteoarthritis and Molecular Mechanism

作　　者：冷明昊[1] 毛慧敏 舒莉[3] LENG Minghao;MAO Huimin;SHU Li(Department of Orthopaedics,Suizhou Central Hospital,Suizhou 441300,Hubei China;Department of Nuclear Medicinc,Suizhou Central Hospital,Suizhou 441300,Hubei China;Department of Orthopaedics,the Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]湖北随州市中心医院骨科,湖北随州441300 [2]随州市中心医院核医学科 [3]新疆医科大学第六附属医院骨科

出　　处：《中国中医骨伤科杂志》2020年第9期16-22,共7页Chinese Journal of Traditional Medical Traumatology & Orthopedics

基　　金：新疆维吾尔自治区自然科学基金项目(2019D01C162)。

摘　　要：目的:探讨多巴胺(DA)对骨关节炎的治疗作用及相关分子机制。方法:SPF级别雄性SD大鼠60只,随机分为模型组、多巴胺5μg/kg组、多巴胺10μg/kg组、多巴胺15μg/kg组、假手术组、阳性对照组。采用右膝关节前韧带交叉切断术建立骨关节炎(OA)大鼠模型,检测大鼠的机械性痛阈值和膝关节直径;采用ELISA法检测大鼠外周血液中白细胞介素(IL)-1β,IL-6和肿瘤坏死因子(TNF)-α含量;采用RT-PCR法检测大鼠关节组织中IL-1β,IL-6,TNF-α,金属基质蛋白酶(MMP)-3,MMP-9和MMP-13 mRNA表达水平;采用HE染色和番红固绿染色检测大鼠关节组织的病理学变化;采用Western Blot法检测大鼠关节组织中MMP-3,MMP-9,MMP-13,Akt,p-Akt,p-Iκ-Bα,Iκ-Bα,p-p65和p65蛋白表达水平。结果:多巴胺显著增加OA大鼠的机械性痛阈值,并减小OA大鼠的膝关节直径,差异有统计学意义(P<0.05);同时下调OA大鼠外周血液中IL-1β,IL-6及TNF-α的表达水平,差异有统计学意义(P<0.05);多巴胺显著下调OA大鼠关节组织中IL-1β,IL-6,TNF-α,MMP-3,MMP-9及MMP-13 mRNA表达水平,并缓解OA大鼠关节组织中炎性细胞浸润和软骨基质降解,差异有统计学意义(P<0.05);除此之外,多巴胺显著下调OA大鼠关节组织中MMP-3,MMP-9,MMP-13,p-Akt/Akt,p-Iκ-Bα/Iκ-Bα及p-p65/p65蛋白表达水平,差异有统计学意义(P<0.05)。结论:多巴胺对骨关节炎治疗具有潜在的价值,且这种作用可能与抑制Akt/NF-κb信号通路活化有关。Objective:To investigate the effect of dopamine(DA)on the treatment of osteoarthritis and related molecular mechanisms.Methods:60 SPF male SD rats were established with osteoarthritis(OA)rat model by right anterior ligament cross-section measure,and the mechanical pain threshold and knee diameter of the rats were measured.Interleukin IL-1β,IL-6 and tumor necrosis factor TNF-αin peripheral blood of rats were detected by ELISA.RT-PCR was used to detect the expression of IL-1β,IL-6,TNF-α,metal matrix proteinase MMP-3,MMP-9 and MMP-13 mRNA in rat joint.Pathological changes in joint tissues of rats were detected by HE and Safranin O staining.Western blot was used to detect MMP-3,MMP-9,MMP-13,Akt,p-Akt,p-Iκ-Bα,Iκ-Bα,p-p65 and p65 protein expression levels in rat joint tissues.Results:Dopamine significantly increased the threshold of mechanical pain in OA rats and reduced the knee joint diameter of OA rats(P<0.05).It down-regulated the expression levels of IL-1β,IL-6,TNF-αin peripheral blood of OA rats(P<0.05).Dopamine significantly down-regulated the mRNA expression levels of IL-1β,IL-6,TNF-α,MMP-3,MMP-9,MMP-13 in joint tissues of OA rats,and relieved inflammatory cell infiltration and cartilage matrix degradation in the joint tissues of OA rats(P<0.05).In addition,Dopamine significantly down-regulated MMP-3,MMP-9,MMP-13,p-Akt/Akt,p-Iκ-Bα/Iκ-Bα,p-p65/p65 protein expression levels(P<0.05).Conclusion:Dopamine has potential value for the treatment of osteoarthritis,and this effect may be related to the inhibition of Akt/NF-κb signaling pathway activation.

关 键 词：多巴胺 骨关节炎 分子机制 

分 类 号：R-33[医药卫生]