EGCG抑制饮食性高脂血症大鼠Angptl3-LPL信号通路的研究

Inhibition effects of EGCG on the Angptl3-LPL pathway in rats fed a cholesterol diet

本研究旨在探讨表没食子儿茶素没食子酸酯(EGCG)的降脂作用与Angptl3-LPL信号通路之间的关系。通过高脂饲料喂养建立高脂血症大鼠动物模型,将正常大鼠按体质量和体脂水平随机分为正常对照组、高脂模型组、EGCG高剂量组(EGCG-H,30 mg·kg^(-1)·d^(-1))、EGCG低剂量组(EGCG-L、15 mg·kg^(-1)·d^(-1))、T0901317组、EGCG-T0901317组(EGCG,30mg·kg^(-1)·d^(-1))。连续灌胃8周后,用生化法检测血清中TG、TC、LDL-C含量,qPCR法检测脂肪组织中脂蛋白脂肪酶(LPL)mRNA和肝组织中Angptl3 mRNA相对表达量,Western blot检测蛋白表达水平。给大鼠口服选择性的LXRs激动剂T0901317后测定肝脏Angptl3 mRNA和蛋白表达水平,评价EGCG对T0901317抑制剂的作用。结果表明,与高脂模型组相比,EGCG(30、15 mg·kg^(-1)·d^(-1))能有效降低大鼠的血脂水平,明显抑制肝脏Angptl3 mRNA和蛋白表达、上调脂肪组织LPL mRNA和蛋白表达水平(P<0.05或P<0.01),且EGCG(30mg·kg^(-1)·d^(-1))可有效抑制由T0901317引起的Angptl3 mRNA和蛋白的表达。本研究从一个新的角度揭示了EGCG通过抑制Angptl3-LPL信号通路来防治与高脂相关性疾病的可能机制,所以以Angptl3-LPL信号通路为调节靶标,可能成为治疗血脂紊乱的一条新途径。

The lipid-lowering effect of EGCG on Angptl3 -LPL pathways was studied by establis- hing dietary hyperlipidemia rat model and EGCG intervention. The hyperlipidemia animal model was set up with high fat food , and the rats were divided randomly into control group, high-fat model group,EGCG high dose group （EGCG-H, 30 mg·kg-1·d-1 ）, EGCG low dose group （EGCG-L,15 mg·kg-1·d-1 ） , T0901317 group and EGCG-T0901317 group （EGCG, 30mg·kg-1·d-1） according to their body quality and lipid levels（n=10） . After 8 weeks administration respectively to three groups of hyperlipidemia rats by gavage, serum TG, TC, LDL-C contents were detected,while expressions of hepatic Angptl3 and adipose LPL mRNA were determined by qPCR,Angptl3 and LPL protein by western bolt. Compared with the model group, EGCG （30, 15 mg·kg-1·d-1i）has a serum cholesterol-lowering function via inhibiting hepatic Angptl3mRNA and protein levels and increasing adipose LPL mRNA and protein levels（P〈0.05 or P〈 0.01 ,and an inhibition in Angptl3 mRNA and protein expression by T0901317. EGCG inhibiting the Angptl3-LPL pathway may be one of the potential mechanisms in treatment of hyperlipidaemia.