非诺贝特对高脂喂养的糖尿病大鼠骨骼肌UCP3基因表达的影响

Effect of fenofibrate on the expression of uncoupling protein 3 gene in skeletal muscle of diabetic rats fed with high fat diet

目的观察长期高脂喂养对糖尿病(DM)大鼠骨骼肌解偶联蛋白3(UCP3)基因表达的影响以及非诺贝特治疗后其表达的变化。方法Wistar大鼠随机分为正常饮食对照组(NC)、DM正常饮食组(DN),DM高脂饮食组(DH)和DM高脂饮食非诺贝特治疗组(DHF)。10wk后留取空腹血浆测定血糖(FPG)、甘油三酯(TG)、游离脂肪酸(FFA)和胰岛素,同时测定骨骼肌细胞内TG和FFA,RT-PCR法测定骨骼肌UCP3 mRNA表达。结果与NC组和DN组相比,DH组大鼠血浆和肌肉内FFA和TG均明显升高,骨骼肌UCP3基因表达明显增加(P<0.01),胰岛素抵抗指数(HOMA2-IR)明显升高(P<0.01)。给予非诺贝特后可以明显改善上述异常(P<0.01),同时观察到骨骼肌内UCP3基因表达较DH组明显增加(P<0.01)。结论高脂喂养可增加糖尿病大鼠血浆脂质水平,引起肌肉组织内脂质沉积,导致胰岛素抵抗(IR)。非诺贝特有降低血浆脂肪酸水平和肌肉内脂质沉积,改善胰岛素敏感性的作用,其作用可能与增强UCP3基因表达有关。

Aim To explore the effect of long-term high fat diet on the expression of uncoupling （ UCP3 ） gene in skeletal muscle of diabetic mellitus （DM） rats, and the effect of the fenofibrate therapy. Method Wistar rats were randomly divided into normal con- trol group （NC,n = 10）, diabetic normal chow group （ DN, n = 12）, Diabetic high fat diet group （ DH, n = 12） and high fat diet plus fenofibrate treatment group （ DHF,n = 12） After 10 weeks, the fasting plasma glucose （ FPG）, free fatty acid （ FFA ）, triglyceride （ TG）, insulin and the content of FFA, TG in muscle were measured. Homeostasis Model Assessment insulin resistance （HOMA2-IR） was applied to assess the status of insulin resistance. The change of the expression of UCP3 in skeletal muscle was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Restilts Compared with NC and DN group, the level of FFA and TG in DH were significantly increased （p 〈 0.01 ） , and this is also true to the expression of UCP3 gene （ P 〈 0.01 ） and HOMA2-IR （ P 〈 0. 01 ）. Comparedwith DH group, the level of FFA and TG both in plasma and muscle of the DHIF group were significantly decreased （ P 〈 0.01 ）. And the insulin sensitivity （ HOMA2-IR ） was improved （ P 〈 0. 01 ）. Moreover, the expression of UCP3 gene was increased （P 〈 0.01 ）. Conclusion High fat diet increase the level of plasma fatty, result in lipid deposition in muscle and insulin resistance （IR）. Fenofibrate treatment lowened the level of plasma TG and FFA and lipid ectopic deposition and improved insulin sensitivity. The effect of improving insulin sensitivity may involve in the overexpression of UCP3 gene.