SREBP-1c激活在细菌脂多糖引起小鼠肝脏脂质沉积中的作用

摘要

To investigate the role of sterol regulatory element-binding protein ( SREBP-lc ) activation in lipopolysaccharide( LPS )-induced hepatic lipid accumulation in the model of LPS-induced inflammation and infection in mice. Methods ICR male mice were randomly divided into 2 groups. The saline-treated mice served as control group,LPS groups were intraperitoneally injected with a single dose of LPS ( 2 mg/kg ). Body weight was assessed and mice were killed at 24 h after LPS treatment. Blood samples were collected, and liver tissues were assessed. The level of triglycerides( TG )and total cholesterol( TCH )were detected in serum and liver. HE staining and oil 0 staining were carried out to assess the change of hepatic histology and lipid accumulation. The level of he- patic fatty acid synthase ( FAS ), acetyl coenzyme A carboxylase ( ACC ) and stearoyl coenzyme A desaturase -1 ( SCD-1 ) mRNA, which were key genes for de novo fatty acid syntheses in liver, were determined by RT-PCR. The expressions of hepatic lipogenesis transcription factors carbohydrate response element binding protein ( ChREBP ) and SREBP-1 c were determined by Western blot. Results The absolute and relative liver weights were significantly increased in LPS-treated mice. The level of serum and hepatic TG were significantly increased in LPS-treated mice. Hepatic histology showed a steatosis associated with mild necrosis and inflammation. Oil 0 staining showed an obvious hepatic lipid accumulation. Moreover, the level of hepatic FAS and ACC mRNA was significantly upreg-ulated in LPS-treated mice. The level of nuclear SREBP-1 c was significantly increased. Conclusion LPS-induced hepatic SREBP-1 c activation, which may contribute to LPS-induced up-regulation of key enzymes for fatty acid synthesis , FAS and ACC, results in hepatic lipid accumulation.%目的 通过建立细菌脂多糖(LPS)致小鼠急性炎症反应模型,观察LPS对小鼠肝脏脂质沉积的影响并初步探讨固醇调节元件结合蛋白-1c(SREBP-1c)激活在LPS引起肝脏脂质沉积中的作用.方法 雄性ICR小鼠随机分为对照组和LPS组,分别经腹腔注射给予生理盐水和LPS(2 mg/kg),LPS处理24 h后称量小鼠体重,眼球取血后剖杀小鼠,取肝脏并称量肝组织重量;检测血清和肝脏甘油三酯(TG)、胆固醇(TCH)含量;HE染色法分析肝脏组织病理学改变;油红O染色法分析肝脏脂质沉积;RT-PCR检测脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC)和硬脂酰辅酶A去饱和酶-1(SCD-1)的mRNA水平;Western blot检测肝脏脂质合成的转录因子碳水化合物反应元件结合蛋白(ChREBP)和SREBP-1c的核蛋白水平.结果 与对照组相比,LPS组小鼠肝脏重量及脏器系数明显增加;血清和肝脏 TG含量明显升高;HE染色显示LPS组小鼠肝脏出现明显脂肪变性、轻度坏死及炎症反应;油红O染色显示LPS组小鼠肝脏发生明显脂质沉积;RT-PCR结果显示LPS明显上调FAS和ACC mRNA水平;Western blot结果显示LPS处理后小鼠肝脏核蛋白SREBP-1c水平明显升高.结论 LPS可能通过激活肝脏SREBP-1c,继而上调从头合成脂肪酸关键酶FAS和ACC,引起小鼠肝脏脂质合成增加,最终导致肝脏脂质沉积.