内脂素对KKAy糖尿病小鼠血浆脂代谢及肝脏胆固醇调节元件结合蛋白1C、激素敏感性脂肪酶表达的影响

Effects of visfatin on plasma lipid metabolism and hepatic SREBP-1C and HSL expression in KKAy diabetic mice

目的通过观察内脂素(Visfatin)对KKAy小鼠胆固醇调节元件结合蛋白1C(SREBP-1C)、激素敏感性脂肪酶(HSL)表达的影响,探讨Visfatin对脂代谢的影响及其作用机制。方法 16只SPF级8周龄雄性KKAy小鼠分为糖尿病模型组(DM组,n=8)及Visfatin组(VF组,n=8)。同时选取16只8周龄的C57BL/6J小鼠分为正常对照组(NC组,n=8)和高脂喂养组(HFD组,n=8)。VF组腹腔注射内脂素重组蛋白,其他组腹腔注射等量磷酸缓冲盐溶液。眼球取血测FPG、FIns、TC、TG、HDL-C及LDL-C等;计算稳态模型IR指数(HOMA-IR)及胰岛素敏感指数(ISI)。测定小鼠肝脏组织SREBP-1C、HSL mRNA及蛋白表达。结果 HFD组FIns、TC、HOMA-IR及LDL-C较NC组升高(P<0.05);DM组FPG、FIns、TC、TG、HOMA-IR及LDL-C较HFD组升高(P<0.05);VF组FPG、TC、TG及LDL-C较DM组降低(P<0.05)。DM组SREBP-1C基因及蛋白表达较NC组升高[(17.94±0.67)vs(205.36±3.00),(0.72±0.07)vs(1.39±0.22),P<0.05],而HSL基因及蛋白表达较NC组降低[(100.00±0.45)vs(69.37±0.36),(1.95±0.65)vs(0.88±0.24),P<0.05]。HFD组与DM组SREBP-1C基因及蛋白表达较NC组升高(P<0.05),而HSL基因及蛋白表达降低(P<0.05);VF组SREBP-1C基因及蛋白表达较DM组降低,HSL基因及蛋白表达较DM组升高(P<0.05)。结论 Visfatin降低血脂水平改善脂代谢,其机制可能是通过下调肝脏中SREBP-1CmRNA、蛋白的表达,上调HSL mRNA、蛋白的表达来实现。

Objective To investigate the effects of visfatin on the hepatic SREBP-1 Cand HSL expression in KKAY mice,and to explore the role and its mechanism of visfatin on lipid metabolism.Methods A total of 16 male KKAy mice（8 weeks old）were selected in this study and divided into two groups：diabetic model group（DM,n=8）and visfatin treatment group（VF,n=8）.Meanwhile,another 16 C57 BL/6 Jmice（8 weeks old）were also selected and divided into two groups：control group（NC,n=8）and high-fat diet group（HFD,n=8）.VF group was injected with recombinant protein visfatin,while NC,HFD and DM group were injected with equal dose of PBS.The blood samples were collected from eyes.FPG,FIns,TG,TC,HDL-C and LDL-C were measured.The homeostasis model assessment（HOMA-IR） and insulin sensitivity inedx（ISI）were calculated.The mRNA and protein expressions of SREBP-1 Cand HSL in hepatic tissues were detected. Results FIns,TC,HOMA-IR and LDL-C were significantly higher in HFD group than in NC group（P〈0.05）.FPG,FIns,TG TC,HOMA-IR and LDL-C were significantly higher in DM group than in HFD group（P〈0.05）.FPG,TC and FIns were significantly lower in VF group than in DM group（P〈0.05）.Compared with NC group,the mRNA and protein expressions of SREBP-1 were increased（P〈0.05）,while the mRNA and protein expressions of HSL were reduced in HFD group（P〈0.05）.Compared with HFD group and NC group,the mRNA and protein expressions of SREBP-1 C were increased（P〈0.05）,while the mRNA and protein expression of HSL were reduced in DM group（P 0.05）.The mRNA and protein expressions of SREBP-1 C was significantly lower in VF group than in DM group（P〈0.05）,while the mRNA and protein expressions of HSL were significantly higher in VF group than in DM group（P〈0.05）. Conclusion Visfatin may reduce the level of lipid profile by down-regulating the mRNA and protein expressions of SREBP-1,and upregulating mRNA and protein expressions of HSL in KKAy mice.