摘要
目的探讨中性粒细胞弹性蛋白酶(NE)在非酒精性脂肪性肝炎(NASH)库普弗细胞(KC)活化中的作用.方法以高脂高胆固醇饮食(HFHC)喂养雄性ApoE-/-(ApoE基因敲除)小鼠16周,建立N ASH模型,低脂饮食(L F D)作为对照组,以NE-/-ApoE-/-(NE,ApoE基因双敲除)小鼠作为观察组。采用血清生化分析和组织学评分评价NASH小鼠肝损伤程度。采用荧光定量RT-PCR、免疫组化检测肝脏炎症,CD68和F4/80表达标志KC细胞活化.结果与对照组比较,模型组(HFHC-ApoE-/-)小鼠体重、肝指数比较均明显增加;血清甘油三酯(TG)、总胆固醇(TC)、谷丙转氨酶(ALT)和谷草转氨酶(AST)明显升高(P<0.05)。肝组织学非酒精性脂肪性肝炎(NASH)积分、炎症因子表达增高(P<0.05)。KC细胞活化CD68和F4/80表达明显增加(P<0.05)。NE基因敲除后,NASH小鼠的体质量、生化指标、肝脏组织学炎症程度以及KC细胞的活化则较模型组明显改善(P<0.05)。结论NE基因敲除可以显著改善NASH小鼠模型以及KC细胞的活化。
Objective To investigate the role of neutrophil elastase(NE)in the activation of Kupffer cell(KC)in nonalcoholic steatohepattis(NASH).Methods Male ApoE-/-(ApoE gene knockout)fed with high-fat and high cholesterol diet(HFHC)for 16 weeks was used to establish NASH model.ApoE-/-mice were fed with low-fat diet(LFD)as control group and NE-/-ApoE-/-(Double knockout of NE and ApoE genes)mice as experimental observation group(P<0.05).Serum biochemical analysis and histological score were used to evaluate the degree of liver injury in NASH mice.Liver inflammation was detected by real-time RT-PCR and immunohistochemistry.The expression of CD68 and F4/80 indicated the activation of KC cells.Results Compared with the control group,the body weight and liver index of model group(HFHC-ApoE-/-)mice were significantly increased,serum triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were significantly increased in the model group.The score of NAS and the expression of inflammatory factors were increased.The expression of CD68 and F4/80 was significantly increased in KC cells.After NE gene knockout,the body weighr,biochemical indexes,histological inflammation degree of liver and the activation of KC cells in NASH mice were significantly improved.Conclusion NE gene knockout can significantly improve the activation of KC cells and NASH mouse model.
出处
《浙江临床医学》
2020年第10期1387-1390,共4页
Zhejiang Clinical Medical Journal
基金
国家自然科学基金资助项目(81570524)。
