SDF-1/CXCR4激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛
SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus
- 中山大学学报（医学科学版） 2021年42卷第3期 页码：373-380
- 作者机构：
1.中山大学附属第一医院麻醉科，广东 广州 510080
2.番禺区中心医院麻醉科，广东 广州 511400
3.广东省骨科学重点实验室，广东 广州 510700
- 作者简介：
魏明，硕士，主治医师，研究方向：临床麻醉与疼痛诊疗，E-mail：wwwmmming@126.com
- 基金信息：广州市卫生局西医类研究项目(20201A01119);广州市中药局研究项目(20202A010026)
DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107
中图分类号： R364.5纸质出版日期：2021-05-20，
收稿日期：2021-03-18，
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魏明,高凤娇,杨琳等.SDF-1/CXCR4激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛[J].中山大学学报（医学科学版）,2021,42(03):373-380.
WEI Ming,GAO Feng-jiao,YANG Lin,et al.SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(03):373-380.
魏明,高凤娇,杨琳等.SDF-1/CXCR4激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛[J].中山大学学报（医学科学版）,2021,42(03):373-380. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107.
WEI Ming,GAO Feng-jiao,YANG Lin,et al.SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(03):373-380. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107.
摘要
目的
2
探讨基质细胞衍生因子1/趋化因子CXC受体4（SDF-1/CXCR4）通路在髓核致炎根性疼痛中的作用及机制。
方法
2
分为三部分：① 26只大鼠随机分为假手术组和模型组，分别行假手术或髓核自体移植。Von Frey 纤维丝测量大鼠机械撤足阈值（PWT）的变化； Western blot法检测大鼠脊髓中SDF-1、CXCR4，磷酸化细胞外信号调节激酶（pERK）和磷酸化蛋白激酶B（pAKT）表达水平；免疫荧光染色定位SDF-1、CXCR4的表达细胞。② 54只大鼠随机分为假手术组、模型组、溶剂组、AMD3100组、SDF-1中和抗体组、对照Ig G组。鞘内注射相应药物，测量大鼠PWT的变化和大鼠脊髓中pERK和pAKT的表达变化。③ 18只大鼠随机分为溶剂组、U0126组、LY294002组，鞘内注射相应药物，测量大鼠PWT的变化。
结果
2
① 髓核自体移植使大鼠PWT下降（
P
＜0.001），脊髓中SDF-1、CXCR4、pERK，pAKT表达上调（
P
＜0.05），SDF-1主要与脊髓中神经元共表达，CXCR4 与神经元和星形胶质细胞共表达。② 鞘内注射SDF-1中和抗体或CXCR4抑制剂AMD3100升高髓核自体移植大鼠的PWT（
P
＜0.05），并使髓核自体移植大鼠脊髓中pERK和pAKT表达下调（
P
＜0.05）。③ 鞘内给予MEK抑制剂U0126或PI3K抑制剂LY294002可升高髓核自体移植大鼠PWT（
P
＜0.05）。
结论
2
SDF-1/CXCR4通过激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛。
Abstract
Objective
2
To investigate the effect and mechanism of SDF-1/CXCR4 in radicular pain induced by autograft of nucleus pulposus.
Methods
2
Three parts were included. ① 26 rats were randomly divided into sham group and model group. Autograft of nucleus pulposus was done in model group. Paw withdrawal threshold （PWT） was tested by von Fray filaments. The expression of SDF-1， CXCR4， pERK and pAKT of spinal cord was tested by western blot. Immunofluorescence staining was used to locate the expression of SDF-1 and CXCR4. ② 54 rats were randomly and equally divided into sham group， model group， vehicle group， SDF-1 neutralizing antibody group， AMD3100 group， and isotype IgG group. Drug was administered intrathecally. PWT and the expression of pERK and pAKT of spinal cord were tested. ③ 18 rats were randomly and equally divided into model group， U0126 group and LY294002 group. Drug was administered intrathecally. PWT was tested.
Results
2
① Autologous nucleus pulposus transplantation in rats reduced PWT （
P
＜0.001） and increased the expressions of SDF-1， CXCR4， pERK and pAKT in spinal cord of rats （
P
＜0.05）. SDF-1 was mainly co-expressed with neuron， while CXCR4 was co-expressed with neuron and astrocyte. ② SDF-1 neutralizing antibody and CXCR4 inhibitor AMD3100 reduced PWT （
P
＜0.05）. The expression of pERK and pAKT in spinal cord of SDF-1 neutralizing antibody group and AMD3100 group was reduced （
P
＜0.05）. ③ Intrathecally administration of MEK inhibitor U0126 or PI3K inhibitor LY294002 reduced PWT （
P
＜0.05）.
Conclusion
2
SDF-1/CXCR4 activates ERK and PI3K/AKT signaling， which contributes to the pathogenesis of radicular pain induced by autograft of nucleus pulposus.
关键词
腰椎间盘突出症髓核根性疼痛基质细胞衍生因子1CXCR4
Keywords
lumbar disc herniationnucleus pulposusradicular painSDF-1CXCR4
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