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

作　　者：沈宸 吴志浩 殷俊[1,2] 朱立麒 张泉 SHEN Chen;WU Zhihao;YIN Jun;ZHU Liqi;ZHANG Quan(College of Veterinary Medicine,Yangzhou University,Yangzhou 225009,China;Collaborative Inmnovation Center for Prevention and Control of Important Animal Epidemics cand Zoonoses in Jiangsu Universities,Yangzhou 225009,China;Afitiated Hospital of Yangzhou University,Yangzhou 225001,China)

机构地区：[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

出　　处：《实验动物与比较医学》2021年第2期122-130,共9页Laboratory Animal and Comparative Medicine

基　　金：江苏省重点研发计划(社会发展)项目(BE2020674)。

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P C R和免疫组织化学法评估肝脏病变情况。结果 H. h+H F D组小鼠血清中TG、A L T和A S T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;H F D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-1β、转化生长因子-β(transforming growth factor-β,TGF-β)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)mRNA转录水平均比其他3组明显升高(均P<0.05),而且α-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。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-1β, transforming growth factor-β(TGF-β) and tumor necrosis factor-α(TNF-α) 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(α-SMA) and collagen type Ⅰ(Collagen Ⅰ) 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.

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 

分 类 号：R-332[医药卫生] Q95-33[生物学—动物学]