肝螺杆菌感染促进高脂饲料诱导的小鼠非酒精性脂肪性肝病进展

doi:10.12300/j.issn.1674-5817.2020.181

实验动物与比较医学 ›› 2021, Vol. 41 ›› Issue (2): 122-130.DOI: 10.12300/j.issn.1674-5817.2020.181

• 论著:人类疾病动物模型 • 上一篇下一篇

肝螺杆菌感染促进高脂饲料诱导的小鼠非酒精性脂肪性肝病进展

沈宸^1,2, 吴志浩^1,2, 殷俊^1,2, 朱立麒^1,2, 张泉^1,2,3

1．扬州大学兽医学院,扬州 225009;
2．江苏高校动物重要疫病与人兽共患病防控协同创新中心,扬州 225009;
3．扬州大学附属医院,扬州 225001

收稿日期:2020-11-02 修回日期:2021-03-10 出版日期:2021-04-25 发布日期:2021-04-30
作者简介:沈宸(1996—), 男, 硕士研究生, 研究方向: 实验动物病原学与比较医学。E-mail: sc875053794@163.com
基金资助:
江苏省重点研发计划(社会发展)项目(BE2020674)

Helicobacter hepaticus Infection Promotes High Fat Diet-induced Non-alcoholic Fatty Liver Disease in Mice

SHEN Chen^1,2, WU Zhihao^1,2, YIN Jun^1,2, ZHU Liqi^1,2, ZHANG Quan^1,2,3

1. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China;
2. Collaborative Innovation Center for Prevention and Control of Important Animal Epidemics and Zoonoses in Jiangsu Universities, Yangzhou 225009, China;
3. Affiliated Hospital of Yangzhou University, Yangzhou 225001, China

Received:2020-11-02 Revised:2021-03-10 Online:2021-04-25 Published:2021-04-30

摘要/Abstract

摘要： 目的探讨肝螺杆菌（Helicobacter hepaticus,H.h）感染对高脂饮食（high fat diet,HFD）诱导非酒精性脂肪性肝病的影响。方法 20只6周龄雄性BALB/c小鼠随机分为4组,每组5只,分别为空白对照组、HFD组、H.h组和H.h+HFD组。H.h+HFD组感染H.h后喂养高脂饲料。各组饲喂12周后处死小鼠,检测各组小鼠血清中三酰甘油（triglyceride,TG）、丙氨酸转氨酶（alanine transaminase,ALT）和天冬氨酸转氨酶（aspartate aminotransferase,AST）的含量,并采用油红O染色、天狼猩红染色、苏木精-伊红染色、实时荧光定量PCR和免疫组织化学法评估肝脏病变情况。结果 H.h+HFD组小鼠血清中TG、ALT和AST水平均明显高于空白对照组（均P<0.05）,且高于H.h组和HFD组（均P<0.05）。H.h+HFD组小鼠的肝脏组织出现脂肪沉积、肝细胞气球样变性和点状坏死灶,胶原纤维大量沉积;H.h组出现炎性细胞聚集和少量胶原纤维沉积;HFD组出现脂滴堆积和脂肪样变,以及少量胶原纤维沉积。H.h+HFD组小鼠肝脏中白细胞介素6（interleukin-6,IL-6）、IL-1?、转化生长因子-?（transforming growth factor-?,TGF-?）和肿瘤坏死因子-〈（tumor necrosis factor-〈,TNF-〈）mRNA转录水平均比其他3组明显升高（均P<0.05）,而且〈-SMA和CollagenⅠ蛋白也出现大量表达。结论 H.h感染可以促进高脂饲料诱导的小鼠非酒精性脂肪性肝病发展。

关键词: 肝螺杆菌, 非酒精性脂肪性肝病, 高脂饲料, 肝纤维化, 小鼠

Abstract: Objective To investigate the effect of Helicobacter hepaticus (H.h) on non-alcoholic fatty liver disease induced by a high fat diet (HFD). Methods Twenty 6-week-old male BALB/c mice were randomly divided into four groups: control group, H.h group, HFD group and H.h+HFD group. The H.h+HFD group was fed a HFD after H.h infection. After 12 weeks of feeding, the levels of triglyceride (TG), alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured. Besides, the liver index was calculated, and oil red O staining, Sirius red staining, hematoxylin-eosin staining, real-time fluorescence quantitative PCR (RT-PCR) and immunohistochemistry were conducted to evaluate liver pathological changes in the liver samples. Results The serum levels of TG, ALT and AST in the H.h+HFD group were significantly higher than those in the control group, H.h group and HFD group (all P<0.05). The livers of mice in the H.h+HFD group showed multiple lesions, fat accumulation, ballooning degeneration and necrosis, collagen fiber deposition. The livers of mice in the H.h group exhibited inflammatory cell aggregation and a small amount of collagen fiber deposition, whereas the livers of mice in the HFD group showed lipid droplets accumulation, steatosis and a small amount of collagen fiber deposition. Moreover, the mRNA levels of interleukin (IL)-6, IL-1?, transforming growth factor-? (TGF-?) and tumor necrosis factor-〈 (TNF-〈) were significantly elevated in the livers of mice in the H.h+HFD group compared to the other three groups (all P<0.05). The expressions of alpha-smooth muscle actin (〈-SMA) and collagen typeⅠ(CollagenⅠ) were significantly increased in the H.h+HFD group. Conclusion H.h infection can promote non-alcoholic fatty liver disease induced by feeding HFD to mice.

Key words: Helicobacter hepaticus, Non-alcoholic fatty liver disease, High-fat diet, Liver fibrosis, Mice

中图分类号:

R-332
Q95-33

沈宸, 吴志浩, 殷俊, 朱立麒, 张泉. 肝螺杆菌感染促进高脂饲料诱导的小鼠非酒精性脂肪性肝病进展[J]. 实验动物与比较医学, 2021, 41(2): 122-130.

SHEN Chen, WU Zhihao, YIN Jun, ZHU Liqi, ZHANG Quan. Helicobacter hepaticus Infection Promotes High Fat Diet-induced Non-alcoholic Fatty Liver Disease in Mice[J]. Laboratory Animal and Comparative Medicine, 2021, 41(2): 122-130.

图/表 5

参考文献

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肝螺杆菌感染促进高脂饲料诱导的小鼠非酒精性脂肪性肝病进展

Helicobacter hepaticus Infection Promotes High Fat Diet-induced Non-alcoholic Fatty Liver Disease in Mice

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