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胰高血糖素样肽1受体在大鼠慢性炎性痛发生机制中的作用
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| 篇名： | 胰高血糖素样肽1受体在大鼠慢性炎性痛发生机制中的作用 |
| TITLE： | |
| 摘要： | 目的：研究胰高血糖素样肽1受体（GLP-1R）在大鼠慢性炎性痛发生机制中的作用。方法：取大鼠随机分为正常对照组、生理盐水1组和完全弗氏佐剂（CFA）1组，另取大鼠随机分为生理盐水2组、CFA2组和（GLP-1R激动药）GLP-1组（5 μg/kg），采用左后足趾侧注射CFA复制大鼠慢性炎性痛模型，后3组大鼠建模后第7天腹腔注射相应药物，连续给药1周。采用Hargreaves热痛仪测定前3组大鼠建模前1 d（－1 d）、建模当天（0 d）和建模后1、3、7、14 d的舔足潜伏期，后3组大鼠建模后8、10、12、14 d的舔足潜伏期，每个时间点6只大鼠。建模后第7天，采用免疫荧光组织化学染色观察模型组大鼠GLP-1R分子的分布情况。采用Western blot法检测前3组大鼠建模后1、3、7、14 d背根神经节（DRG）中GLP-1R蛋白的表达水平，后3组大鼠建模后14 d DRG中GLP-1R、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）及IL-1β蛋白的表达水平，每个时间点3只大鼠。结果：与正常对照组和生理盐水1组比较，CFA1组大鼠建模后1、3、7、14 d的舔足潜伏期明显缩短（P＜0.01），DRG中GLP-1R蛋白表达水平明显降低（P＜0.01），－1、0 d的舔足潜伏期差异无统计学意义（P＞0.05）。GLP-1R分子与NeuN双重标记明显，且与降钙素基因相关肽（CGRP）阳性神经元双重标记明显，与植物凝集素B4 （IB4）阳性神经元未见明显双重标记。与生理盐水2组比较，CFA2组大鼠建模后8、10、12、14 d的舔足潜伏期明显缩短（P＜0.01），建模后14 d DRG中GLP-1R蛋白表达水平明显降低（P＜0.01），TNF-α、IL-6及IL-1β蛋白表达水平明显升高（P＜0.01）。与CFA2组比较，GLP-1组大鼠建模后8、10、12、14 d的舔足潜伏期明显延长（P＜0.05或P＜0.01），建模后14 d DRG中GLP-1R蛋白表达水平明显升高（P＜0.01），TNF-α、IL-6及IL-1β蛋白表达水平明显降低（P＜0.05或P＜0.01）。结论：GLP-1R分子主要表达于DRG中的CGRP阳性神经元，其表达水平随慢性疼痛的发生与发展而逐渐降低，且升高GLP-1R表达能够有效缓解慢性炎性痛，其可能与降低DRG中炎症因子的表达有关。 |
| ABSTRACT： | OBJECTIVE： To study the role of glucagon-like peptide 1 receptor （GLP-1R） on chronic inflammatory pain mechanism in rats. METHODS： The rats were randomly divided into normal control group， normal saline group 1 and complete Freund’s adjuvant （CFA） group 1. Other rats were randomly divided into normal saline group 2， CFA 2 group and （GLP-1R agonist） GLP-1 group （5 μg/kg）. Chronic inflammatory pain model was induced by left hind toe side injection of CFA. The latter 3 groups were given relevant medicine intraperitoneally on the 7th day after modeling， for consecutive a week. The licking incubation of the former 3 groups were determined by Hargreaves thermal pain instrument 1 d before modeling （－1 d）， on modeling day （0 d）， 1， 3， 7， 14 d after modeling； the licking incubation of the latter 3 groups were determined 8， 10， 12， 14 d after modeling； those of each 6 rats were determined at each time point. 7 d after modeling， distribution of receptor GLP-1R molecule in model group was observed by immunofluorescence double labeling. Western blot method was used to detect the expression of GLP-1R protein in dorsal root ganglia （DRG） of rats in former 3 groups 1， 3， 7 and 14 d after modeling. The expression of GLP-1R， TNF-α， IL-6 and IL-1β protein in DRG of rats were also determined in latter 3 groups 14 d after modeling； those of each 3 rats were determined at each time point. RESULTS： Compared with normal control group and normal saline group 1， licking incubation of CFA group 1 was shortened significantly 1， 3， 7， 14 d after modeling （P＜0.01）， and the protein expression of GLP-1R in DRG was decreased significantly （P＜0.01）； there was no statistical significance in licking incubation －1 and 0 d （P＞0.05）. GLP-1R molecules were double labeled with NeuN and calcitonin gene-related peptide （CGRP）-positive neurons no significant double marker was found between GLP-1R molecules and phytohemagglutinin B4 positive neurons. Compared with normal saline group 2， licking incubation of CFA group 2 was shortened significantly 8， 10， 12， 14 d after modeling （P＜0.01）； the protein expression of GLP-1R in RG was decreased significantly 14 d after modeling （P＜0.01）； the protein expression of TNF-α， IL-6 and IL-1β were increased significantly （P＜0.01）. Compared with CFA group 2， licking incubation of GLP-1 group was prolonged significantly 8， 10， 12， 14 d after modeling （P＜0.05 or P＜0.01）； the protein expression of GLP-1R in DRG was increased significantly 14 d after modeling （P＜0.01）， and the protein expression of TNF-α， IL-6 and IL-1β were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： GLP-1R molecule is mainly expressed in CGRP-positive neurons of DRG. The expression level of GLP-1 receptor gradually decreases with the occurrence and development of chronic pain. The increase of GLP-1R expression can effectively relieve chronic inflammatory pain， which is related with reducing reduce the expression of inflammatory factors in DRG. |
| 期刊： | 2018年第29卷第19期 |
| 作者： | 王健，牛云圃，崔佳，王磊，樊婷婷，张维 |
| AUTHORS： | WANG Jian，NIU Yunpu，CUI Jia，WANG Lei，FAN Tingting，ZHANG Wei |
| 关键字： | 胰高血糖素样肽1受体；完全弗式佐剂；慢性炎性痛；炎症因子；大鼠 |
| KEYWORDS： | Glucagon-like peptide 1 receptor； Complete Freund’s adjuvant； Chronic inflammatory pain； Inflammatory factor； Rat |
| 阅读数： | 349 次 |
| 本月下载数： | 6 次 |
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