脂多糖加速饮食所致非酒精性脂肪肝小鼠的炎症和氧化应激  

Inflammation and oxidative stress of accelerated diet of lipopolysaccharide induced non-alcoholic fatty liver disease in mice

作　　者：张威[1] 史国兵[1] 张敬一[1] 

机构地区：[1]沈阳军区总医院药剂科,沈阳110840

出　　处：《实用药物与临床》2014年第10期1243-1246,共4页Practical Pharmacy and Clinical Remedies

摘　　要：目的本研究旨在探讨脂多糖在非酒精性肝炎(NASH)模型中的作用。方法采用胆碱蛋氨酸缺乏(Methionine choline deficient,MCD)饮食诱导的小鼠NASH模型。18只雄性C57BL/6小鼠分为3组,MCS+Saline组给予正常饮食+腹腔生理盐水,MCD+Saline组给予胆碱蛋氨酸缺乏饮食+腹腔注射生理盐水,MCD+LPS组给予胆碱蛋氨酸缺乏饮食+腹腔注射1 mg/kg脂多糖,共2周。在最后一次注射的6 h之后处死小鼠,取血清和肝组织。进行肝脏HE染色和Sirius Red染色,观察肝组织病理学变化。并测定血清中血清丙氨酸氨基转移酶(ALT)和肿瘤坏死因子-α(TNF-α)的含量。结果 MCD造成小鼠肝脏中大量脂肪滴的沉积和炎症细胞浸润,血清ALT升高,脂多糖注射进一步加重肝细胞凋亡,肝脏中TBARS进一步升高,血清TNF-α含量显著增加。结论在MCD所致非酒精性脂肪肝炎模型小鼠中,腹腔注射脂多糖引起血清中TNF-α升高,进一步加重细胞凋亡,因此,脂多糖在非酒精性脂肪肝炎的进程中具有重要作用,提示临床预防或治疗非酒精性脂肪肝炎需要关注患者肠道菌群失调症状。Objective To investigate the effect of lipopolysaccharide on a non-alcoholic steatohepatitis（NASH） model. Methods Male C57BL/6 mice were divided into 3 groups. MCS ＋Saline group was fed with methionine-choline-sufficient（MCS） diet and intraperitoneally injected with saline;MCD ＋ Saline group was fed with methionine-choline-deficient（MCD） diet and intraperitoneally injected with saline;MCD ＋ LPS group was fed with MCD diet and intraperitoneally injected with 1 mg /kg lipopolysaccharide（LPS） twice weekly. Then mice were sacrificed 6 h after last injection. The changes on liver histology was assessed by HE and Sirius Red staining. ALT and TNF-α of serum were dectected. Results MCD diet could significantly increase the hepatic fat deposition and inflammatory cell infiltration,and raise the serum ALT level of the MCD diet-fed mice. Apoptosis of hepatocytes and TBARS content of MCD mice were accelerated by LPS injection,and the TNF-α was increased. Conclusion LPS up-regulates TNF-αproduction of NASH mice induced by MCD. LPS may play a key role in the pathogenesis of NASH. The alteration of intestinal flora should be considered during the treatment and prevention of NASH.

关 键 词：凋亡 脂多糖 非酒精性脂肪肝炎 肿瘤坏死因子-Α 

分 类 号：R575.5[医药卫生—消化系统]