摘要
目的探讨Salubrinal对肥胖诱导的非酒精性脂肪肝的疗效。方法选用30只雌性C57BL/6小鼠,随机分为对照(SCD)组、高脂饮食(HF)组和高脂饮食治疗(HF+S)组。HF组和HF+S组小鼠给予含脂量为60%的高脂饮食,4周肥胖诱导后,HF+S组接受Salubrinal皮下注射4周。实验过程中每周测量动物体成分变化,采取静脉血检测血脂指标,收集皮下、内脏脂肪和肝脏进行湿质量测定。为探索Salubrinal对肝脏的影响及作用机制,通过HE、油红O染色观察肝脏病理改变,Western blot检测肝组织e IF2α信号通路相关蛋白Bip、p-eIF2α、eIF2α、ATF4和CHOP的表达。结果与SCD组比较,HF组小鼠的血脂水平和脂肪堆积明显增加,Salubrinal治疗后,脂质紊乱情况减轻。同时,肝脏组织学检查显示,Salubrinal可以明显缓解肝脂肪变性严重程度并抑制异常脂质沉积。此外,Western blot分析表明,Salubrinal通过增加Bip、p-eIF2α/eIF2α和ATF4的表达量,降低CHOP的表达水平抑制内质网应激。结论Salubrinal能够有效缓解肥胖和肝脂肪变性,并通过eIF2α信号通路调控内质网应激而影响脂质代谢。
ObjectiveTo investigate the effect of salubrinal on obesity-induced non-alcoholic fatty liver disease.MethodsThirty female C57 BL/6 mice were randomly divided into three groups:standard chow diet(SCD)group,high-fatdiet(HF)group and HF with salubrinal(HF+S)group.The HF and HF+S groups were given a high-fat diet(fat content:60%).After 4-week obesity induction,salubrinal was subcutaneously injected for the next 4 weeks in HF+S group.Duringthe experiment,the changes in animal body compositions were measured regularly.Serum lipid parameters were examinedthrough venous blood.The abdominal subcutaneous fat,periuterine and perirenal fat,and liver were collected for wet massdetermination.The pathological changes of the liver tissues were observed by H&E and oil red O staining for investigatingthe effect and mechanism of salubrinal on the hepatic steatosis.The expressions of proteins related to e IF2αsignaling(Bip,p-e IF2α,e IF2α,ATF4 and CHOP)were detected by Western blot assay.ResultsCompared to the SCD group,the serumlipid level and the fat accumulation were increased in HF and HF+S groups.After treatment with salubrinal,the lipiddisorder was relieved.Also,the histological severity of hepatic steatosis in the liver was suppressed in response to salubrinal.In addition,Western blot analysis showed that salubrinal inhibited endoplasmic reticulum stress by increasing theexpressions of Bip,p-e IF2αand ATF4 with a decrease level of CHOP.ConclusionSalubrinal can effectively alleviateobesity and non-alcoholic fatty liver disease and regulate lipid metabolism by altering endoplasmic reticulum stress throughe IF2αsignaling.
作者
张诗琪
刘大全
李心乐
张平
ZHANG Shi-qi;LIU Da-quan;LI Xin-le;ZHANG Ping(Department of Anatomy and Histology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China;Key Laboratory of Hormones and Development(Ministry of Health),Tianjin Key Laboratory of Metabolic Diseases;Tianjin Key Laboratory of Spine and Spinal Cord)
出处
《天津医药》
CAS
北大核心
2020年第5期375-380,共6页
Tianjin Medical Journal
基金
天津市教委科研计划项目(2017KJ223)。
