6-姜烯酚通过抑制SCD1表达改善db/db小鼠肝脏脂肪变性的研究

目的探讨6-姜烯酚对db/db小鼠肝脏脂质代谢的影响及机制。方法将24只db/db小鼠随机分为模型组、6-姜烯酚低剂量组(10 mg·kg^-1)和6-姜烯酚高剂量组(40 mg·kg^-1),每组8只,雌雄各半;另取8只BKS小鼠(雌雄各半)作为正常对照组;灌胃给药,每日1次,连续21 d。采用酶法检测肝脏组织甘油三酯(TG)含量;采用油红O染色法检测肝脏组织脂质沉积情况;采用实时荧光定量聚合酶链式反应(qPCR)法检测碳水化合物反应元件结合蛋白(ChREBP)、固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合酶(FAS)、乙酰辅酶A羧化酶(ACC)、二酰基甘油酰基转移酶2(DGAT2)、硬脂酰辅酶A去饱和酶1(SCD1)、酰基辅酶A氧化酶(ACOX)及肉碱棕榈酰基转移酶1a(CPT1a)的mRNA表达;采用Western Blot法和免疫荧光染色法检测肝脏组织SCD1蛋白的表达情况。结果与正常对照组比较,模型组小鼠肝脏组织的TG含量和油红O染色面积以及SREBP-1c、ACC、FAS、DGAT2、SCD1 mRNA表达显著上调(P<0.05,P<0.01),ACOX、CPT1a mRNA表达显著下调(P<0.05)。与模型组比较,6-姜烯酚高剂量组的小鼠肝脏组织TG含量和油红O染色面积明显减少(P<0.01),SCD1在mRNA水平和蛋白水平的表达均显著下调(P<0.05,P<0.01),与免疫荧光染色法检测结果一致。结论6-姜烯酚能够改善db/db小鼠的肝脏脂质沉积,其机制可能与下调SCD1的表达有关。

6-Shogaol Improves Hepatic Steatosis in db/db Mices by Inhibiting SCD1 Expression

Objective To investigate the effects and mechanisms of 6-shogaol on hepatic steatosis in db/db mice.MethodsTwenty-four db/db mice were randomized into three groups(twelve animals per sex, db/db): model group,low-and high-dose 6-shogaol(10 mg·kg^-1,SL;40 mg·kg^-1,SH)groups,four animals per sex in each group. Eight BKS mice were used as a normal control group(four animals per sex,BKS). Intragastric administration were carried out once a day for 3 weeks. Enzymatic method was used for the examination of hepatic triglyceride(TG).Liver lipid deposition was observed by oil red O staining. The mRNA levels of carbohydrate response elementbinding protein(ChREBP),sterol regulatory element binding protein-1 c(SREBP-1 c),fatty acid synthase(FAS),acetyl-CoA carboxylase(ACC),diacylglycerol acyltransferase2(DGAT2),stearoyl-CoA desaturase1(SCD1),acylCoenzyme A oxidase(ACOX),and carnitine palmitoyltransferase1 a(CPT1 a),were measured by quantitative realtime polymerase chain reaction(qPCR). The protein expression of SCD1 in liver tissue were analyzed by Western Blot and immunofluorescence staining.ResultsCompared with the BKS group(the normal group),db/db mice had significantly increased TG concentration, oil red O staining area and the mRNA levels of SREBP-1 c, FAS,DGAT2, ACC, SCD1, and significantly down regulated mRNA levels of ACOX and CPT1 a in liver tissue(P<0.05,P<0.01). Furthermore,compared with the db/db group,the TG concentration,oil red O staining area(P<0.05), and the expressions of SCD1 in mRNA, protein levels had significantly decreased in the SH group(P<0.05,P<0.01). The expression of SCD1 protein was further confirmed by immunofluorescence staining.Conclusion6-shogaol can inhibit liver lipid deposition in db/db mice which may associate with inhibiting the SCD1 expression.