Nesfatin-1在小鼠胃癌模型中的表达及其在胃癌合并抑郁中的作用

Nan Zhang, Jiangbo Li, Huiling Wang, Ling Xiao, Yanyan Wei, Jing He, Gaohua Wang
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引用次数: 11

摘要

背景:癌症患者抑郁症状的发生率较高。抑郁症还可以通过神经内分泌-免疫网络系统影响癌症的发生、发展和结局。目的:通过建立小鼠胃癌模型,研究Nesfatin-1在胃癌伴抑郁小鼠血浆和脑组织中的表达水平及其在胃癌伴抑郁的发病机制中的作用。方法:将18只小鼠随机分为正常对照组(NCG)、胃癌无应激模型组(GCNS)和胃癌合并应激模型组(GCS)。GCNS组小鼠在正常喂养5周后皮下接种小鼠前胃癌(MFC),建立皮下移植瘤模型。GCS组慢性不可预测轻度应激(CUMS) 5周后,皮下接种MFC建立皮下移植肿瘤模型,持续1周。采用空地试验、蔗糖偏好试验和强迫游泳试验(FST)评价小鼠行为。采用酶联免疫吸附法(ELISA)和Western Blot检测大鼠血浆和脑组织中Nesfatin-1的浓度。结果:GCS组体重增加量明显低于GCNS组(t=-3.39, pt=-6.33, pt=-2.94, p=0.01)。在野外试验中,GCS组的水平移动距离小于GCNS组(t=-2.50, p=0.025), GCS和GCNS均小于NCG组(t=-5.87, pt=-3.38, p=0.004)。GCS组死亡时间较GCNS组和NCG组长(t=2.56, p=0.022;t = 3.84, p = 0.002)。NCG组和GCS组大鼠中脑、海马和血浆中Nesfatin-1水平均显著高于GCNS组。GCS组的Nesfatin-1浓度显著高于NCG组。结论:无应激条件下胃癌小鼠脑组织和血浆中Nesfatin-1水平明显降低。CUMS应激可诱导胃癌小鼠出现抑郁行为,脑组织和血浆中Nesfatin-1水平升高。因此,Nesfatin-1可能与胃癌应激性抑郁的发病机制有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The Level of Nesfatin-1 in a Mouse Gastric Cancer Model and Its Role in Gastric Cancer Comorbid with Depression.

Background: The incidence of depressive symptoms is higher in cancer patients. And depression can also affect the occurrence, development and outcome of cancer through the neuroendocrine-immune-network system.

Objective: To study the level of Nesfatin-1 in the plasma and brain tissue and its role in the pathogenesis in gastric cancer comorbid with depression using a mouse gastric cancer model.

Methods: 18 mice were randomly divided into the normal control group (NCG), gastric cancer without stress model group (GCNS), and gastric cancer combined with stress model group (GCS). The mice of the GCNS group were inoculated subcutaneously with mouse forestomach carcinoma (MFC) after 5 weeks of nomal feeding to establish a model of subcutaneous transplantation tumor. After 5 weeks of chronic unpredicted mild stress (CUMS) in the GCS group, subcutaneous inoculation of MFC was used to establish a subcutaneous transplantation tumor model for 1 week. Evaluation of mice behavior was performed by open field test, sucrose preference test and forced swimming test (FST). Determination of Nesfatin-1 concentration in plasma and brain tissue was carried out using enzyme linked immunosorbent assay (ELISA) and Western Blot.

Results: The weight increment in the GCS group was significantly lower than that in the GCNS group (t=-3.39, p<0.001). And both GCS and GCNS were lower than the NCG group (t=-6.33, p<0.001; t=-2.94, p=0.01). In the open field test, the horizontal moving distance of the GCS group was less than that of the GCNS group (t=-2.50, p=0.025), and both GCS and GCNS were smaller than the NCG group (t=-5.87, p<0.001; t=-3.38, p=0.004). The dead time of the GCS group was longer than that of the GCNS and the NCG groups (t=2.56, p=0.022; t=3.84, p=0.002). The Nesfatin-1 level in the middle brain, hippocampus and plasma was significantly higher in NCG group and GCS group than in the GCNS group. The concentration of Nesfatin-1 in the GCS group was significantly higher than that in the NCG group.

Conclusions: There is a decrease of Nesfatin-1 level in brain tissue and plasma in mice with gastric cancer without stress. CUMS stress can induce depressive behavior in gastric cancer mice, and increase the level of Nesfatin-1 in brain tissue and plasma. Therefore, Nesfatin-1 may be related to the pathogenesis of gastric cancer stress related depression.

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