枸杞多糖基于IRE1-α/JNK/AP-1信号通路对肥胖小鼠慢性炎症的影响

Effect of Lycium barbarum Polysaccharide on Chronic Inflammation in Obese Mice via the IRE1-α/JNK/AP-1 Signaling Pathway

摘要: 目的：肥胖作为能量代谢失衡引发的慢性低度炎症，其发生与内质网应激(Endoplasmic Reticulum Stress, ERS)之间存在密切关联。本研究旨在探讨枸杞多糖(Lycium barbarum Polysaccharide, LBP)通过调控IRE1α/JNK/AP-1信号通路改善高脂饮食诱导肥胖小鼠炎症反应的分子机制。方法：实验采用C57BL/6J雄性小鼠建立12周高脂饮食肥胖模型，随机分为普通饮食组(N)、假手术组(J)、模型对照组(G)及LBP高(GH)、中(GM)、低(GL)剂量干预组。经4周灌胃干预后，检测脂肪组织形态变化，结合Western blot、ELISA和免疫组化技术分析内质网应激关键蛋白(IRE1α, JNK, AP-1)及炎症因子(TNF-α, CRP, IL-6)的表达水平。结果：LBP可以有效抑制IRE1α/JNK/AP-1信号通路的异常激活，以及下调脂肪组织炎症因子表达。结论：本研究证实LBP能够通过调控内质网应激IRE1α/JNK/AP-1信号轴缓解肥胖相关炎症反应，且中低剂量干预效果优于高剂量，为开发基于内质网应激调控的肥胖治疗策略提供了实验依据。

Abstract: Objective: Obesity, characterized by chronic low-grade inflammation resulting from energy metabolism dysregulation, is closely associated with endoplasmic reticulum stress (ERS). This study aimed to elucidate the molecular mechanism by which Lycium barbarum polysaccharide (LBP) ameliorates high-fat diet (HFD)-induced inflammatory responses in obese mice through modulation of the IRE1α/JNK/AP-1 signaling pathway. Methods: Male C57BL/6J mice were fed an HFD for 12 weeks to establish an obesity model, followed by randomization into six groups: normal diet (ND), sham-operated (SO), HFD model control (MC), and LBP high- (LBP-H), medium- (LBP-M), and low-dose (LBP-L) intervention groups. After 4 weeks of intragastric administration, adipose tissue morphology was assessed, and key ERS-related proteins (IRE1α, JNK, AP-1) and inflammatory cytokines (TNF-α, CRP, IL-6) were quantified via Western blot, ELISA, and immunohistochemistry. Results: LBP significantly suppressed aberrant activation of the IRE1α/JNK/AP-1 pathway and downregulated pro-inflammatory cytokine expression in adipose tissue. Notably, medium- and low-dose LBP interventions demonstrated superior efficacy compared to the high-dose group. Conclusion: These findings demonstrate that LBP alleviates obesity-associated inflammation by targeting the ERS-mediated IRE1α/JNK/AP-1 signaling axis, with optimal therapeutic effects achieved at moderate doses. This study provides experimental evidence for developing ERS-targeted therapeutic strategies against obesity-related metabolic disorders.