背景:脂肪和肌肉组织消瘦概述了肿瘤进展过程中的恶病质过程。已知交感神经系统(SNS)可促进肿瘤进展,研究表明,它也可能通过脂肪消耗导致癌症相关恶病质(CAC)的能量消耗。
方法:我们通过腹膜内施用6-羟基多巴胺对L5178Y-R荷瘤雄性BALB/c小鼠进行交感神经切除,炎症,以及CAC和肿瘤进展的分子指标。
结果:肿瘤负荷与恶病质指标相关,包括10.5%的体重指数(BMI)下降,40.19%肩胛骨间,54%腹股沟,和37.17%的内脏脂肪组织损失,12%的食物摄入量减少,血浆炎性细胞因子IL-6和IFN-γ分别显着增加(p=0.038和p=0.0037)。荷瘤小鼠的交感神经切除术与BMI减弱和内脏脂肪组织丢失有关,肩胛骨间Ucp-1基因表达降低至基础水平,mmp-9相对基因表达减少2.6倍,与无交感神经切除小鼠对照组相比。
结论:在小鼠模型中,SNS有助于CAC相关的形态测量和脂肪组织改变,并促进肿瘤进展。
BACKGROUND: Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting.
METHODS: We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression.
RESULTS: Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group.
CONCLUSIONS: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.