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大麻素受体1阻断对非酒精性脂肪性肝病小鼠脂肪组织和肝组织中脂肪因子及促炎细胞因子浓度的影响。

The effect of cannabinoid receptor 1 blockade on adipokine and proinflammatory cytokine concentration in adipose and hepatic tissue in mice with nonalcoholic fatty liver disease.

作者信息

Jorgačević Bojan, Vučević Danijela, Vesković Milena, Mladenović Dušan, Vukićević Dušan, Vukićević Rada Ješić, Todorović Vera, Radosavljević Tatjana

机构信息

a Institute of Pathophysiology "Ljubodrag Buba Mihailović", Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.

b Institute of Digestive Diseases, Clinical Centre of Serbia, 11000 Belgrade, Serbia.

出版信息

Can J Physiol Pharmacol. 2019 Feb;97(2):120-129. doi: 10.1139/cjpp-2018-0607. Epub 2019 Jan 23.

DOI:10.1139/cjpp-2018-0607
PMID:30673308
Abstract

In high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD), there is an increase in the endocannabinoid system activity, which significantly contributes to steatosis development. The aim of our study was to investigate the effects of cannabinoid receptor type 1 blockade on adipokine and proinflammatory cytokine content in adipose and hepatic tissue in mice with NAFLD. Male mice C57BL/6 were divided into a control group fed with a control diet for 20 weeks (C, n = 6) a group fed with a HFD for 20 weeks (HF, n = 6), a group fed with a control diet and treated with rimonabant after 18 weeks (R, n = 9), and a group fed with HFD and treated with rimonabant after 18 weeks (HFR, n = 10). Rimonabant significantly decreased leptin, resistin, apelin, visfatin, interleukin 6 (IL-6), and interferon-γ (IFN-γ) concentration in subcutaneous and visceral adipose tissue in the HFR group compared to the HF group (p < 0.01). Rimonabant reduced hepatic IL-6 and IFN-γ concentration as well as plasma glucose and insulin concentration and the homeostatic model assessment index in the HFR group compared to the HF group (p < 0.01). It can be concluded that the potential usefulness of CB1 blockade in the treatment of HFD-induced NAFLD is due to modulation of the adipokine profile and proinflammatory cytokines in both adipose tissues and liver as well as glucose metabolism.

摘要

在高脂饮食(HFD)诱导的非酒精性脂肪性肝病(NAFLD)中,内源性大麻素系统活性增加,这对脂肪变性的发展有显著影响。我们研究的目的是探讨1型大麻素受体阻断对NAFLD小鼠脂肪组织和肝脏组织中脂肪因子和促炎细胞因子含量的影响。将雄性C57BL/6小鼠分为对照组,喂食对照饮食20周(C组,n = 6);高脂饮食组,喂食高脂饮食20周(HF组,n = 6);对照组在18周后喂食对照饮食并接受利莫那班治疗(R组,n = 9);高脂饮食组在18周后喂食高脂饮食并接受利莫那班治疗(HFR组,n = 10)。与HF组相比,利莫那班显著降低了HFR组皮下和内脏脂肪组织中瘦素、抵抗素、脂联素、内脂素、白细胞介素6(IL-6)和干扰素-γ(IFN-γ)的浓度(p < 0.01)。与HF组相比,利莫那班降低了HFR组肝脏IL-6和IFN-γ的浓度以及血浆葡萄糖和胰岛素浓度以及稳态模型评估指数(p < 0.01)。可以得出结论,CB1阻断在治疗HFD诱导的NAFLD中的潜在作用是由于调节了脂肪组织和肝脏中的脂肪因子谱和促炎细胞因子以及葡萄糖代谢。

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