高脂暴露可激活JAK2/STAT3信号通路而促进髓核细胞凋亡

High-fat exposure promotes nucleus pulposus cell apoptosis by activating the JAK2/STAT3 signaling pathway

摘要

目的 椎间盘退变（Intervertebral disc degeneration，IDD）与腰痛有关，而后者是导致残疾的主要原因。肥胖已成为IDD发展的危险因素。肥胖相关的IDD可能与过度的机械负荷、炎症和代谢紊乱有关，但潜在的分子机制尚不清楚。肥胖可激活JAK/STAT信号通路。本研究旨在探讨肥胖是否通过激活JAK2/STAT3信号通路促进IDD的发病。 方法 利用高脂饮食（High-fat diet，HFD）构建大鼠肥胖模型。HE染色和免疫组织化学分析研究软骨病理变化。利用棕榈酸（Palmitic acid，PA）刺激髓核细胞（Nucleus pulposus，NP）。利用流式细胞仪检测细胞凋亡。利用蛋白质印迹法来检测Bax、Bcl-2、IL-6、JAK2及STAT3蛋白表达。 结果 HFD暴露可诱导肥胖和促进IDD发展。HFD同时也激活JAK2/STAT3信号通路的表达，诱导NP细胞凋亡。利用JAK2抑制剂Ruxolitinib可有效中和PA对NP细胞凋亡的作用。 结论 HFD诱导的肥胖可通过激活JAK2/STAT3信号通路促进IDD的病理发展。

Abstract

Objective : Intervertebral disc degeneration （IDD） has been associated with low back pain， which is the leading cause of disability. Obesity has become a risk factor for IDD development. Obesity-associated IDD might be related to excessive mechanical loading， inflammation， and metabolic disorders. The underlying mechanism of obesity in promoting the pathogenesis of IDD is still unclear. Obesity has been associated with the activation of the JAK/STAT signaling pathway. This study aims to investigate whether obesity promoted IDD pathogenesis by activating the JAK2/STAT3 signaling pathway. Methods High-fat diet （HFD）-induced rat obesity models were duplicated. Hematoxylin and eosin （HE） staining and immunohistochemistry （IHC） analysis were performed to study the pathological changes of cartilage. Palmitic acid （PA） was used to stimulate the nucleus pulposus （NP）. Cell apoptosis was detected by a flow cytometer. Western blotting assays were used to determine the protein expression of Bax， Bcl-2， IL-6， JAK2， and STAT3. Results In this study， it was found that an HFD could induce obesity and IDD development. In addition， high-fat exposure activated the JAK2/STAT3 signaling pathway and stimulated NP cell apoptosis. However， the JAK2 inhibitor Ruxolitinib could compromise the effects of PA on NP cell apoptosis. Conclusion HFD-induced obesity may promote the pathogenesis of IDD by activating the JAK2/STAT3 signaling pathway.

关键词

椎间盘退变 / 肥胖 / 髓核 / JAK2/STAT3信号通路 / 细胞凋亡

Key words

Intervertebral disc degeneration / Obesity / Nucleus pulposus / JAK2/STAT3 signaling pathway / Cell apoptosis