HIF-1α对非酒精性脂肪性肝病小鼠肝组织的影响*

doi:10.3969/j.issn.1672-5069.2021.05.015

摘要/Abstract

摘要： 目的探讨缺氧诱导因子1α(HIF-1α)在非酒精性脂肪性肝病(NAFLD)进展中的作用。方法将30只雄性C57BL/6J小鼠随机分为对照组、高脂饮食模型组和蛋氨酸-胆碱缺乏饮食(MCD)模型组,每组10只,建立非酒精性脂肪性肝炎(NASH)模型,分别取肝组织行组织病理学检查,采用缺氧探针检测肝组织缺氧程度,采用Real-time PCR法检测肝组织HIF-1α mRNA水平,采用Western blot法检测肝组织HIF-1α蛋白表达。另取小鼠肝星状细胞JS-1细胞,分为对照组、腺病毒载体组和HIF-1α ShRNA腺病毒载体感染组,采用MTT法检测细胞活性,采用Real-time PCR法检测细胞1型胶原(COL1)和3型胶原(COL3)、TNF-α、IL-1β和TGF-β1 mRNA水平。结果缺氧探针染色显示高脂饮食模型组和MCD模型组小鼠肝组织染色阳性率分别为85%和78%,显著高于对照组的7%(P<0.05);高脂饮食模型组和MCD模型组小鼠肝组织HIF-1α mRNA水平分别为对照组小鼠的2.1倍和1.6倍(P<0.05),HIF-1α蛋白表达水平也相应地增强;HIF-1α ShRNA腺病毒载体感染细胞活力仅为对照组的37%(P<0.05),细胞COL1、COL3、TNF-α、IL-1β、TGF-β1 mRNA水平也显著降低(P<0.05)。结论 HIF-1α能够促进小鼠NAFLD进展,抑制HIF-1α表达可能能延缓NAFLD进展,值得进一步研究。

关键词: 非酒精性脂肪性肝炎, 缺氧诱导因子1α, 高脂饮食, 蛋氨酸-胆碱缺乏饮食, 小鼠, JS-1细胞

Abstract: Objective This paper aimed to investigate the effect of hypoxia-inducible factor 1α(HIF-1α) in the development of nonalcoholic steatohepatitis (NASH). Methods Thirty male 57BL/6J mice were randomly divided into control, high-fat diet and methionine-choline-deficient diet (MCD) group, and the NASH model was established. The liver tissues were obtained for histological examination and hypoxyprobe staining. The HIF-1α mRNA and protein expression were respectively detected by Real-time PCR and Western blotting. The hepatic stellate cells, JS-1, were obtained and divided into control, adenoviral vector-infected and HIF-1α ShRNA adenovirus-infected group. The MTT test was applied for cell living assay. The collagen type 1 (COL1) and type 3 (COL3), TNF-α, IL-1βand TGF-β1 mRNA levels were detected by Real-time PCR. Results The hypoxyprobe staining showed that the percentages of positive staining in the high-fat diet and MCD diet groups were85% and 78%, significantly higher than 7% in the control(P<0.05); the HIF-1α mRNA levels in the two groups were 2.1 fold and 1.6 fold higher than in the control (P<0.05), and the HIF-1α protein expression was also greatly intensified; the cell viability in the HIF-1α ShRNA adenovirus-infected group was only 37%(P<0.05) compared to in the control, and the COL1, COL3, TNF-α, IL-1β and TGF-β1 mRNA decreased greatly compared to in the control(P<0.05). Conclusion HIF-1α might facilitate development of NASH, while needs further investigation.

Key words: Nonalcoholic steatohepatitis, Hypoxia-inducible factor 1α, High-fat diet, Methionine-choline-deficient diet, Mice, JS-1 cells

李妍, 陆伦根, 蔡晓波. HIF-1α对非酒精性脂肪性肝病小鼠肝组织的影响^*[J]. 实用肝脏病杂志, 2021, 24(5): 665-668.

Li Yan, Lu Lungen, Cai Xiaobo. Effect of HIF-1α on development of nonalcoholic steatohepatitis in mice and in vitro[J]. Journal of Practical Hepatology, 2021, 24(5): 665-668.

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HIF-1α对非酒精性脂肪性肝病小鼠肝组织的影响^*

Effect of HIF-1α on development of nonalcoholic steatohepatitis in mice and in vitro

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