盐诱导激酶1过表达对高脂饮食诱导的肥胖大鼠肝脏脂代谢紊乱的调节机制  

Regulation mechanism of overexpression of salt-inducible kinase 1 on hepatic lipid metabolism disorders in high-fat diet induced obese rats

作　　者：周璞 付薇 谢凌波 李倩[1] 邓稀予 Zhou Pu;Fu Wei;Xie Lingbo(Sichuan Academy of Medical Sciences,East Branch of Sichuan People's Hospital,Chengdu 610100)

机构地区：[1]四川省医学科学院·四川省人民医院东院,成都610100

出　　处：《安徽医科大学学报》2021年第3期439-444,共6页Acta Universitatis Medicinalis Anhui

基　　金：四川省卫生与计划生育委员会科研项目(编号:150218)。

摘　　要：目的研究过表达盐诱导激酶1(SIK1)对高脂饮食诱导的肥胖大鼠肝脏脂代谢紊乱的可能调节机制。方法将40只SD大鼠随机分为Control组(10只)和建模组(30只),将高脂饲料喂养12周造模成功后的大鼠随机分为Obesity组、Obesity+LV组、Obesity+LV-SIK1组,Obesity+LV组、Obesity+LV-SIK1组分别通过尾静脉注射慢病毒空白质粒以及慢病毒介导的SIK1过表达质粒,继续高脂饲料喂养8周;完成后取尾静脉空腹血肝功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)]、脂代谢指标[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、炎症细胞因子[肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS)、白细胞介素-6(IL-6)、IL-10]水平,取肝脏组织用HE染色和油红O染色观察肝组织病理损伤及脂肪堆积情况,并利用Western blot检测肝组织中凋亡标记蛋白Caspase-3、Caspase-9以及生酯基因SREBP-1c、FASN、ACC1的表达情况。结果与Control组相比,Obesity组大鼠体质量及血清中ALT、AST、TC、TG、LDL-C、TNF-α、iNOS、IL-6、IL-10水平升高(P<0.05),HDL-C水平降低(P<0.05),肝组织出现明显的结构破坏和脂肪堆积,并且肝组织中cleaved-Caspase-3/Caspase-3、cleaved-Caspase-9/Caspase-9、SREBP-1c、FASN、ACC1蛋白表达水平升高(P<0.05);与Obesity组相比,Obesity+LV-SIK1组大鼠体质量及血清中ALT、AST、TC、TG、LDL-C、TNF-α、iNOS、IL-6水平降低(P<0.05),HDL-C、IL-10水平升高(P<0.05),肝组织结构破坏和脂肪堆积程度降低,cleaved-Caspase-3/Caspase-3、cleaved-Caspase-9/Caspase-9、SREBP-1c、FASN、ACC1蛋白表达水平降低(P<0.05)。结论高脂饮食诱导的肥胖大鼠肝组织受损且有大量脂肪堆积,过表达SIK1后能够降低生酯基因表达,改善脂代谢紊乱,减少脂肪堆积对肝组织的损伤。Objective To study the possible regulation mechanism of overexpression of salt-inducible kinase 1(SIK1)on hepatic lipid metabolism disorders(LMD)in obese rats induced by high-fat diet(HFD).Methods Forty SD rats were randomly divided into Control group(10 cases)and modeling group(30 cases).They were fed with HFD for 12 weeks,and those with successful modeling were randomly divided into Obesity group,Obesity+LV group and Obesity+LV-SIK1 group.Obesity+LV group and Obesity+LV-SIK1 group were injected with lentiviral blank plasmid and lentivirus-mediated SIK1 overexpression plasmid through tail vein,respectively,and then fed with HFD for 8 weeks.Fasting blood from tail vein was applied to detect levels of liver function indexes[(alanine aminotransferase,ALT),(aspartate aminotransferase,AST)],lipid metabolism indexes[(total cholesterol,TC),(triglycerides,TG),(high density lipoprotein cholesterol,HDL-C),(low density lipoprotein cholesterol,LDL-C)]and inflammatory cytokines[(tumor necrosis factor-α,TNF-α),(inducible nitric oxide synthase,iNOS),(interleukin-6,IL-6),IL-10].The pathological damage and fat accumulation in liver tissues were observed by HE staining and oil red O staining.The expression of apoptosis marker proteins(Caspase-3,Caspase-9)and adipogenesis genes(SREBP-1c,FASN,ACC1)in liver tissue was detected by Western blot.Results Compared with Control group,body mass,levels of serum ALT,AST,TC,TG,LDL-C,TNF-α,iNOS,IL-6 and IL-10 increased in Obesity group(P<0.05),while HDL-C level decreased(P<0.05).There was significant structural damage and fat accumulation in liver tissues,and the expression levels of cleaved-Caspase-3/Caspase-3,cleaved-Caspase-9/Caspase-9,SREBP-1c,FASN and ACC1 proteins in liver tissues increased(P<0.05).Compared with Obesity group,body mass,levels of serum ALT,AST,TC,TG,LDL-C,TNF-α,iNOS and IL-6 decreased in Obesity+LV-SIK1 group(P<0.05),while levels of HDL-C and IL-10 increased(P<0.05).The structure destruction and fat accumulation in liver tissues reduced.The expression levels of cleave

关 键 词：肥胖 高脂饮食 盐诱导激酶1 生酯基因 

分 类 号：R589.2[医药卫生—内分泌]