通经定晕丸阻断颈椎病大鼠NF-κB激活MCP-1/CCR2通路及TNF-α及IL-1β、IL-6表达的研究

doi:10.12092/j.issn.1009-2501.2018.04.002

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (4): 370-376.doi: 10.12092/j.issn.1009-2501.2018.04.002

通经定晕丸阻断颈椎病大鼠NF-κB激活MCP-1/CCR2通路及TNF-α及IL-1β、IL-6表达的研究

王先海^1,3，李珍斌¹，李小妹²，张建国¹，石新民¹，许海燕²，冯旻璐²，石孟琼³

¹荆州市公安县中医医院骨外科，荆州 434300，湖北； ²三峡大学生物与制药学院，宜昌 443002，湖北； ³三峡大学医学院基础医学实验中心，宜昌 443002，湖北

收稿日期:2017-07-31 修回日期:2017-08-11 出版日期:2018-04-26 发布日期:2018-04-13
通讯作者: 石孟琼，女，学士，高级实验师，研究方向：中药药理学。 Tel: 0717-6397818 E-mail: shmq0212@126.com
作者简介:王先海，男，硕士，主任医师，研究方向:中医外科学。 Tel: 0716-5225381 E-mail: w-xhai@163.com
基金资助:
湖北省卫计委项目(JX2013014)

Study of Tongjing dingyunwan blocking NF-κB activation on the MCP-1/CCR2 signaling pathway and expressions of TNF-α, IL-1β, IL-6 in the cervical spondylosis rats

WANG Xianhai^1,3, LI Zhenbin ¹, LI Xiaomei², ZHANG Jianguo ¹, SHI Xinmin1, XU Haiyan2, FENG Minlu2, SHI Mengqiong3

¹ Orthopeadic Surgery, Hospital of Traditional Chinese Medicine of Gongan County, Jingzhou 434300,Hubei, China; ²College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, Hubei, China;³ Experimental Center of Basic Medicine, Medical Science College, China Three Gorges University, Yichang 443002, Hubei, China

Received:2017-07-31 Revised:2017-08-11 Online:2018-04-26 Published:2018-04-13

摘要/Abstract

摘要：

目的:研究通经定晕丸阻断颈椎病大鼠核因子-κB(NF-κB)激活单核细胞趋化蛋白-1(MCP-1)/趋化因子受体-2(CCR2)通路及肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)表达的影响。方法:用手术的方法制作颈椎病大鼠模型，用通经定晕丸(5.0和10.0 g/kg)和颈复康冲剂(0.84 g/kg)灌胃给药，每天1次，连续4周，每天观察实验大鼠一般状况。4周后检测，腹主动脉取血，进行血液黏度，血液中TNF-α、IL-1β和IL-6含量分析；取颈椎椎间盘进行组织形态学分析；实时定量PCR检测颈椎椎间盘组织中MCP-1和CCR2的mRNA表达，Western blot检测椎间盘组织中NF-κBp65蛋白表达。结果: 通经定晕丸(5.0和10.0 g/kg)和颈复康冲剂(0.84 g/kg)可显著改善颈椎病模型大鼠的一般状况，降低血液低切黏度值、中切黏度值、高切黏度值，促炎因子TNF-α、IL-1β和IL-6含量及椎间盘组织中MCP-1、CCR2和NF-κBp65的mRNA和蛋白表达(P<0.05或P<0.01)，减轻促炎因子对椎间盘造成的损伤，降低颈椎间盘高度和退变程度，降低纤维环裂隙、髓核、细胞数量、软骨厚度，其中以通经定晕丸10.0 g/kg剂量组作用效果更为显著。结论:通经定晕丸对颈椎病模型大鼠具有较好的治疗的作用，其作用机制与降低血液黏度，抑制MCP-1/CCR2信号通路激活、NF-κB活化及TNF-α、IL-1β和IL-6的生成相关。

关键词: 通经定晕丸, 颈椎病, 核因子-κB, 单核细胞趋化蛋白-1/趋化因子受体-2通路, 促炎因子

Abstract:

AIM: To investigate Tongjing dingyunwan blocking nuclear factor-κB (NF-κB) activation on the MCP-1/CCR2 signaling pathway and expressions of TNF-α, IL-1β, IL-6 in the cervical spondylosis rats. METHODS: The cervical spondylosis model was established through operative method. Therapeutic groups were given Tongjing dingyunwan (5.0 g/kg and 10.0 g/kg) and and Jingfukang granule (0.84 g/kg), once a day for four weeks, the general condition of rat was observed. After oral administration of Tongjing dingyunwan for four weeks, blood viscosity, serum TNF-α, IL-1β, and IL-6 were measured; Cervical intervertebral disc morphology was analyzed by HE staining; Real-time PCR was applied to detect the mRNA expressions of MCP-1 and CCR2, protein expression of NF-κBp65 in intervertebral disk tissue were detected by western blotting. RESULTS: Tongjing dingyunwan (5.0 g/kg and 10.0 g/kg) and Jingfukang granule (0.84 g/kg) might significantly improve the general condition of the cervical spondylosis rats, decrease blood low shear viscosity, shear viscosity, viscosity value, serum TNF-α, IL-1β, IL-6 contents and the mRNA and protein expressions of MCP-1, CCR2 and NF-κBp65 in intervertebral disk tissue (P<0.05, P<0.01, respectively), alleviate the proinflammatory cytokine on intervertebral disc injury, reduce the height and degeneration of the cervical intervertebral disc, reduce the fracture of the fibrous ring, the nucleus pulposus, the number of cells and the thickness of the cartilage, especially Tongjing Dingyunwan 10.0 g/kg group. CONCLUSION: Tongjing dingyunwan has a better therapeutic effect on cervical spondylosis rats. Its mechanism is mainly related to reducing blood viscosity, inhibiting the MCP1/CCR2 signaling pathway, activation of NF-κB, and productions of TNF-α, IL-1β, IL-6.

Key words: Tongjing dingyunwan, cervical spondylosis, nuclear factor-κB, MCP-1/CCR2 signaling pathway, proinflammatory cytokine

中图分类号:

R965.2

王先海，李珍斌，李小妹，张建国，石新民，许海燕，冯旻璐，石孟琼. 通经定晕丸阻断颈椎病大鼠NF-κB激活MCP-1/CCR2通路及TNF-α及IL-1β、IL-6表达的研究[J]. 中国临床药理学与治疗学, 2018, 23(4): 370-376.

WANG Xianhai, LI Zhenbin, LI Xiaomei, ZHANG Jianguo, SHI Xinmin, XU Haiyan, FENG Minlu, SHI Mengqiong . Study of Tongjing dingyunwan blocking NF-κB activation on the MCP-1/CCR2 signaling pathway and expressions of TNF-α, IL-1β, IL-6 in the cervical spondylosis rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(4): 370-376.

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通经定晕丸阻断颈椎病大鼠NF-κB激活MCP-1/CCR2通路及TNF-α及IL-1β、IL-6表达的研究

Study of Tongjing dingyunwan blocking NF-κB activation on the MCP-1/CCR2 signaling pathway and expressions of TNF-α, IL-1β, IL-6 in the cervical spondylosis rats

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