| Exendin-4调控烧伤小鼠炎性反应及多器官损害的交感神经机制 |
| 投稿时间：2017-07-04 修订日期：2017-07-22 点此下载全文 |
| 引用本文：计小静,张庆红,王丽雪,郝济伟,董宁,祝筱梅,卢中秋,姚咏明.Exendin-4调控烧伤小鼠炎性反应及多器官损害的交感神经机制[J].医学研究杂志,2018,47(7):37-42 |
| DOI：
10.11969/j.issn.1673-548X.2018.07.009 |
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| 基金项目:国家自然科学基金资助项目（81272089、81372054）；国家重点研发计划项目（2017YFC1103302）；全军"十二五"计划重点项目（BWSl2J050） |
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| 中文摘要:目的 探讨胰高血糖素样肽（GLP-1）的长效类似物Exendin-4（Ex-4）对烫伤小鼠生存率、炎性反应和器官损伤的影响及其交感神经调控机制。方法 BALB/C小鼠随机分为烫伤组和假伤组，分别行93℃ 15%总体表面积（TBSA）的Ⅲ度烫伤和37℃假伤。烫伤前30min腹腔注射β2肾上腺素能受体阻断剂普萘诺尔（prop，30mg/kg），伤后30min立即腹腔注射Ex-4（2.4nmol/kg）。24h后处死动物留取肺脏和血清，生化法检测肝肾功能，ELISA法检测外周血及肺部炎性因子TNF-α、MCP-1和IL-10水平；分离脾脏单个核细胞，观察核蛋白NF-κB p65蛋白表达；此外，烫伤小鼠随机分组观察Ex-4对动物72h存活情况的影响。结果 Ex-4处理的烫伤小鼠病死率有增加趋势。Ex-4对假伤组肺组织炎性细胞因子没有显著影响，但可显著增加烫伤动物肺脏TNF-α、MCP-1和IL-10水平，且此效应可被prop阻断。Ex-4可抑制假伤小鼠血清TNF-α、IL-10水平，而促进烫伤组血清TNF-α、MCP-1、IL-10水平（P<0.05），且烫伤组prop干预后，反而增强了Ex-4的促细胞因子分泌作用。Ex-4可显著增加烫伤小鼠肝肾功能损伤指标AST/ALT和UR/Cr （P<0.05），并能被prop阻断；而对假伤组无明显影响。Ex-4能显著上调烫伤小鼠脾脏细胞核NF-κB p65蛋白表达（P<0.05），且此效应可被prop阻断。结论 Ex-4可通过交感神经机制促进局部组织器官的炎性反应以及器官损伤，Ex-4和激活的肾上腺素能受体共同激活cAMP-PKA-NF-κB信号转导途径，进而调节全身炎性反应。 |
| 中文关键词:烧伤 胰高血糖素样肽-1 炎性反应 交感神经系 |
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| Sympathetic Nervous System Mechanism Underlying Exendin-4 on Inflammatory Response and Multiple Organ Dysfunction in Mice after Thermal Injury |
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| Abstract:Objective To investigate the regulation of glucagon-like peptide-1 (GLP-1) analogue Exendin-4 (Ex-4) on inflammatory response and organ damage in burned mice and its possible sympathetic regulatory mechanism. Methods Male BALB/C mice were randomly divided into thermal injury group and sham-thermal group. The thermal injury model was carried out by exposing the back skin of 15% total body surface area (TBSA) to 93℃ water for 7 second, while in sham-thermal model the mice were immersed in 37℃ water. Propranolol (prop) (30mg/kg) was i.p. injected prior to thermal injury, then Ex-4 (2.4nmol/kg) was injected i.p. 30 minutes after scalding. The survival number of mice was recorded every 2h until 72h. Kaplan-Merer was used to analyze the survival rate. Levels of TNF-α, MCP-1 and IL-10 in serum and lungs were determined by ELISA, and changes in ALT, AST, UR and Cr values were observed. In addition, the expression of NF-κB in purified splenic T lymphocytes of scalded and sham injured mice was detected by Western blot. Results Treatment with Ex-4 markedly reduced the survival rate and immune function of T lymphocytes in burn mice. In lung tissues, levels of TNF-α, MCP-1 and IL-10 were significantly elevated by Ex-4 in burned mice (P<0.05), and was restored by pretreatment with prop. Serum levels of TNF-α, IL-10 and IL-10 were significantly increased by Ex-4 (P<0.05), which was potentiated by prop intervention in thermal mice. Ex-4 significantly increased AST/ALT and UR/Cr levels in burned mice, and was restored by pretreatment with prop. Ex-4 obviously up-regulated the expression of nuclear p65 protein in the splenic T lymphocytes from burned mice, which was restored by pretreatment with prop. Conclusion Ex-4 can potentiate the inflammatory reaction in burn injury and aggravate its organ damage via the sympathetic nervous mechanism. |
| keywords:Burn injury Glucagon-like peptide-1 Inflammation response Sympathetic nervous system |
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