PDF(Pubmed)
Abstract：
UNASSIGNED: It is well established that discogenic low back pain (DLBP) is often caused by the inflammatory response during intervertebral disc degeneration (IDD). However, it remains unclear how inflammatory mediators such as Interleukin-6 (IL-6) are involved in discogenic pain caused by degeneration and intervertebral disc (IVD) metabolism. The purpose of this study is to study the relationship between IL-6 and Transmembrane protein 100 (TMEM100), and to analyze the different metabolites and metabolic pathways in various rat intervertebral discs by metabonomics.
UNASSIGNED: We established a rat model of IDD-DLBP by disc punctures and PBS infusion to examine the rat pain behaviors. Intervertebral disc tissues were harvested for molecular biology experiments to explore the relationship between IL-6 and TMEM100. High-resolution mass spectrometry (HRMS) was performed for untargeted metabolomics, and nuclear magnetic resonance spectroscopy metabolomics (MRS) for differential metabolites and metabolic pathways.
UNASSIGNED: The results showed a significant decrease in vonFrey test, hot plate test and acetone test (P < 0.05). The expression of IL-6 and TMEM100 in DLBP model was significantly higher than that in sham control group and IDD discs without PBS infusion group (P < 0.05). There were 15 major contributing metabolites identified in the DLBP intervertebral discs through metabolomic studies, involving 6 major metabolic pathways. The main differential metabolites included nitric oxide (NO), ammonia, and lactic acid as the metabolic endpoints; and the differential metabolic pathways included the glycine-serine-threonine (Gly-Ser-Thr), which is gradually weakened with the progression of inflammation.
UNASSIGNED: The change of TMEM100 expression mediated by il-6 is related to the Gly-Ser-Thr metabolic axis and plays an important role in the relief of discogenic pain.
UNASSIGNED: We established a rat model of IDD-DLBP by disc punctures and PBS infusion to examine the rat pain behaviors. Intervertebral disc tissues were harvested for molecular biology experiments to explore the relationship between IL-6 and TMEM100. High-resolution mass spectrometry (HRMS) was performed for untargeted metabolomics, and nuclear magnetic resonance spectroscopy metabolomics (MRS) for differential metabolites and metabolic pathways.
UNASSIGNED: The results showed a significant decrease in vonFrey test, hot plate test and acetone test (P < 0.05). The expression of IL-6 and TMEM100 in DLBP model was significantly higher than that in sham control group and IDD discs without PBS infusion group (P < 0.05). There were 15 major contributing metabolites identified in the DLBP intervertebral discs through metabolomic studies, involving 6 major metabolic pathways. The main differential metabolites included nitric oxide (NO), ammonia, and lactic acid as the metabolic endpoints; and the differential metabolic pathways included the glycine-serine-threonine (Gly-Ser-Thr), which is gradually weakened with the progression of inflammation.
UNASSIGNED: The change of TMEM100 expression mediated by il-6 is related to the Gly-Ser-Thr metabolic axis and plays an important role in the relief of discogenic pain.
摘要：
UNASSIGNED：众所周知，椎间盘源性下腰痛（DLBP）通常是由椎间盘退变（IDD）期间的炎症反应引起的。然而,目前尚不清楚白细胞介素-6(IL-6)等炎症介质如何参与由退变和椎间盘(IVD)代谢引起的椎间盘源性疼痛.目的研究IL-6与跨膜蛋白100(TMEM100)的关系,并通过代谢组学方法分析大鼠椎间盘中不同的代谢产物和代谢途径。
UNASSIGNED：我们通过椎间盘穿刺和PBS输注建立了大鼠IDD-DLBP模型，以检查大鼠的疼痛行为。收集椎间盘组织进行分子生物学实验，探讨IL-6与TMEM100的关系。高分辨率质谱（HRMS）用于非靶向代谢组学，和核磁共振波谱代谢组学（MRS）的差异代谢物和代谢途径。
UNASSIGNED：结果显示vonFrey检验显着下降，热板试验和丙酮试验(P<0.05)。DLBP模型中IL-6和TMEM100的表达明显高于假对照组和未输注PBS的IDD椎间盘组（P<0.05）。通过代谢组学研究，在DLBP椎间盘中发现了15种主要的代谢产物，涉及6个主要代谢途径。主要的差异代谢物包括一氧化氮（NO），氨,和乳酸作为代谢终点；差异代谢途径包括甘氨酸-丝氨酸-苏氨酸（Gly-Ser-Thr），随着炎症的进展逐渐减弱。
UNASSIGNED：il-6介导的TMEM100表达的变化与Gly-Ser-Thr代谢轴有关，在缓解盘源性疼痛中起重要作用。
UNASSIGNED：我们通过椎间盘穿刺和PBS输注建立了大鼠IDD-DLBP模型，以检查大鼠的疼痛行为。
UNASSIGNED：结果显示vonFrey检验显着下降，
UNASSIGNED：il-6介导的TMEM100表达的变化与Gly-Ser-Thr代谢轴有关，在缓解盘源性疼痛中起重要作用。
