[1]冷明昊 毛慧敏 舒莉△.多巴胺对骨关节炎的治疗作用及相关分子机制研究[J].中国中医骨伤科杂志,2020,28(09):16-22.
 LENG Minghao MAO Huimin SHU Li.Study on Efficacy of Dopamine for Osteoarthritis and Molecular Mechanism[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2020,28(09):16-22.
点击复制

多巴胺对骨关节炎的治疗作用及相关分子机制研究()
分享到:

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第28卷
期数:
2020年09期
页码:
16-22
栏目:
实验研究
出版日期:
2020-09-10

文章信息/Info

Title:
Study on Efficacy of Dopamine for Osteoarthritis and Molecular Mechanism
文章编号:
1005-0205(2020)09-0016-07
作者:
冷明昊1 毛慧敏2 舒莉3△
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
Author(s):
LENG Minghao1 MAO Huimin2 SHU Li3△
1Department of Orthopaedics,Suizhou Central Hospital,Suizhou 441300,Hubei China; 2Department of Nuclear Medicine,Suizhou Central Hospital,Suizhou 441300,Hubei China; 3Department of Orthopaedics,the Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China.
关键词:
多巴胺 骨关节炎 分子机制
Keywords:
dopamine osteoarthritis molecular mechanism
分类号:
R-33
文献标志码:
A
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5 μg/kg组、多巴胺10 μg/kg组、多巴胺15 μg/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。
Abstract:
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-α in 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-α in 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.

参考文献/References:

[1] VINA E R,KWOH C K.Epidemiology of osteoarthritis:literature update[J].Curr Opin Rheumatol,2018,30(2):160-167.
[2] 王锴,董雪,林剑浩.影响膝关节骨关节炎患者生活质量预后因素的队列研究[J].中华骨科杂志,2019,39(18):1149-1156.
[3] 邢丹,林剑浩.中国骨关节炎研究现状及热点[J].中华骨科杂志,2018,38(3):179-185.
[4] HAQ S A,DAVATCHI F,DAHAGHIN S,et al.Development of a questionnaire for identification of the risk factors for osteoarthritis of the knees in developing countries.A pilot study in Iran and Bangladesh.An ILAR–COPCORD phase Ⅲ study[J].Int J Rheum Dis,2010,13(3):203-214.
[5] 何方舟,张伟滨.非甾体类抗炎药对中国骨关节炎患者疗效及胃肠道不良反应的Meta分析[J].中华关节外科杂志,2018,12(1):69-76.
[6] LOESER R F,COLLINS J A,DIEKMAN B O.Ageing and the pathogenesis of osteoarthritis[J].Nat Rev Rheumatol,2016,12(7):412-420.
[7] PRIETO-ALHAMBRA D,JUDGE A,JAVAID M K,et al.Incidence and risk factors for clinically diagnosed knee,hip and hand osteoarthritis:influences of age,gender and osteoarthritis affecting other joints[J].Ann Rheum Dis,2014,73(9):1659-1664.
[8] 何玉祥.复方倍他米松联合塞来昔布治疗膝关节骨性关节炎的临床研究[J].现代药物与临床,2019,34(6):1839-1842.
[9] RUNEGAARD A H,FITZPATRICK C M,WOLDBYE D P D6,et al.Modulating dopamine signaling and behavior with chemogenetics:concepts,progress,and challenges[J].Pharmacological Reviews,2019,71(2):123-156.
[10] WANG B,CHEN T,LI G,et al.Dopamine alters lipopolysaccharide-induced nitric oxide production in microglial cells via activation of D1-like receptors[J].Neurochemical research,2019,44(4):947-958.
[11] YAN Y Q,JIANG W,LIU L,et al.Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome[J].Cell,2015,160(1/2):62-73.
[12] PAGENSTERT G,KNUPP M,VALDERRABANO V,et al.Realignment surgery for valgus ankle osteoarthritis[J].Oper Orthop Traumatol,2018,21(1):425-432.
[13] RODRIGUES T A,FREIRE A O,BONFIM B F,et al.Strontium ranelate as a possible disease-modifying osteoarthritis drug:a systematic review[J].Braz J Med Biol Res,2018,51(8):e7440.
[14] 谢志平,李宗文,刘宁.创伤性骨关节炎大鼠血清生化指标及软骨病理学观察[J].中华地方病学杂志,2018,37(9):699-701.
[15] 王晓磊,武晔,姜淑华,等.通痹胶囊联合针刺治疗膝骨关节炎[J].国际中医中药杂志,2019,41(2):141-145.
[16] VAN DALEN S C,BLOM A B,SLÖETJES A W,et al.Interleukin-1 is not involved in synovial inflammation and cartilage destruction in collagenase-induced osteoarthritis[J].Osteoarthritis Cartilage,2017,25(3):385-396.
[17] 李宏军,施源,何敏,等.千草方熏洗对膝骨关节炎大鼠软骨YAP/Smad3表达的影响[J].中国病理生理杂志,2019,35(5):933-939.
[18] WEI X L,DUAN Y W,LIU Y X,et al.Onshore-offshore wind energy resource evaluation based on synergetic use of multiple satellite data and meteorological stations in Jiangsu province,China[J].Front Earth Sci-Prc,2019,13(1):132-150.
[19] ARASAPAM G,SCHERER M,COOL J C,et al.Roles of COX-2 and iNOS in the bony repair of the injured growth plate cartilage[J].J Cell Biochem,2006,99(2):450-461.
[20] DORRINGTON M G,FRASER I D C.NF-κB signaling in macrophages:dynamics,crosstalk,and signal integration.[J].Front Immunol,2019,10:705.
[21] 李剑峰,张君,黑光,等.肌内效贴对早中期膝骨关节炎患者关节液炎性因子水平的影响[J].中华老年医学杂志,2018,37(10):1126.
[22] KOMATSU W,ITOH K,AKUTSU S,et al.Nasunin inhibits the lipopolysaccharide-induced pro-inflammatory mediator production in RAW264 mouse macrophages by suppressing ROS-mediated activation of PI3K/Akt/NF-κB and p38 signaling pathways[J].Biosci Biotech Bioch,2017,81(10):1956-1966.
[23] YAMAGUCHI K,KUMAKURA S,MURAKAMI T,et al.Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells[J].Int J Mol Med,2017,39(3):687-692.
[24] 张媛媛,蒋昕钰,李西海,等.基于PI3K/Akt信号通路探讨电针对膝骨关节炎模型大鼠软骨细胞凋亡的影响[J].康复学报,2019,29(4):34-40.
[25] ZHOU M,LI P,KANG Q,et al.Shen-Yuan-Dan capsule inhibiting inflammatory reaction by regulating insulin receptor substrate 1/PI3K/Akt/NF-kB signaling pathway in apoliprotein E knockout mice fed with a high-fat diet[J].Acta Cardiologica Sinica,2017,33(3):285-291.

备注/Memo

备注/Memo:
(收稿日期:2020-03-16)基金项目:新疆维吾尔自治区自然科学基金项目(2019D01C162) 通信作者 E-mail:huwentingsj@163.com
更新日期/Last Update: 2020-09-10