摘要
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ACCmRNA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。
Objective To investigate the role of sterol regulatory element-binding protein （SREBP-1c） 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 O staining were carried out to assess the change of hepatic histology and lipid accumulation. The level of hepatic 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 significant- ly 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 upregulated in LPS-treated mice. The level of nuclear SREBP-lc was significantly increased. Conclusion LPS-induced hepatic SREBP-lc activation, which may contribute to LPS-induced up-regulation of key enzymes for fatty acid synthesis, FAS and ACC, results in hepatic lipid accumulation.
出处
《安徽医科大学学报》
CAS
北大核心
2011年第12期1227-1231,共5页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:30973544、81001480)
安徽省自然科学基金(编号:090413142)
安徽省高校省级自然科学研究重点项目(编号:KJ2011A159)
安徽医科大学校科学研究基金(编号:2010xkj016)
