利拉鲁肽对促动脉粥样硬化饮食喂养大鼠大动脉的保护作用及对肝脏PGC-1α表达的影响

摘要

Objective To observe the effects of liraglutide on the macrovascular lesions in rats fed with promoting athero‐sclerosis diet and the expression of PGC‐1αin liver and its possible mechanism. Methods In total ,60 specific pathogen free SD male rats were randomly divided into 4 groups:Normal diet group ,promoting atherosclerosis diet group ,promoting atheroscle‐rosis diet + low‐dose liraglutide intervention group ,promoting atherosclerosis diet + high‐dose liraglutide intervention group. The rats were correspondingly given ordinary diet or promoting atherosclerosis diet for 12 weeks. The body weight ,fast‐ing blood sugar and serum lipid level were measured at the end of experiment.The intimamedia thickness (IMT)of abdominal a‐orta was detected by four‐dimensional ultrasound and HE staining. The expression of PGC‐1αin liver was measured by immuno‐histochemisty ,Western blot and RT‐PCR.Results Compared with the control group ,the body weight ,FPG ,FINS ,LDL‐C and insulin resistance index (HOMA‐IR)of rats on high fat diet were significantly increased.The IMT of abdominal aorta was in‐creased in rats fed with high fat diet.liraglutide intervention ameliorated those biochemical indicators and the IMT of abdominal aorta in a dose dependent manner. The expression levels of PGC‐1αgene and protein in liver were decreased in all HFD groups as compared with control group. PGC‐1α expression was significantly lower in HFD group than in liraglutide intervention group ,and the expression in low‐dose liraglutide group was lower than that in high dose group.Conclusion Liraglutide showed a protective effect on the IMT of abdominal aorta in the rats fed with promoting atherosclerosis diet in a dose dependent man‐ ner. The protective effect of liraglutide on macrovascular lesions may be related to the increase of the PGC‐1αexpression in liv‐er.%目的：观察胰高血糖素样肽‐1（GLP‐1）类似物利拉鲁肽对促动脉粥样硬化饮食喂养大鼠大血管的保护作用，探讨利拉鲁肽对肝脏过氧化物酶增殖物激活受体γ激活蛋白‐1α（PGC‐1α）表达的影响。方法将60只清洁级SD雄性大鼠随机分为正常对照组、促动脉粥样硬化饮食组、促动脉粥样硬化饮食＋低剂量利拉鲁肽（50μg／kg ）干预组、促动脉粥样硬化饮食＋高剂量利拉鲁肽（200μg／kg ）干预组，分别予以正常饮食、促动脉粥样硬化饮食、不同剂量利拉鲁肽处理12周。检测大鼠血糖、血脂、胰岛素水平，四维彩超及苏木精‐伊红（H E ）染色检测大鼠腹主动脉病变情况，免疫组化、Western blot及RT‐PCR检测肝脏PGC‐1α蛋白及基因表达情况。结果①与对照组相比，促动脉粥样硬化饮食组大鼠体重明显增加，血糖、低密度脂蛋白胆固醇（LDL‐C）、胰岛素抵抗指数（HOMA‐IR）升高，腹主动脉内中膜厚度增加，但无明显斑块形成；利拉鲁肽干预组大鼠体重有所下降、各项生化指标均有改善、腹主动脉内中膜增厚情况减轻，以高剂量利拉鲁肽干预组改善更明显（P＜0.05）。②与对照组相比，其余3组肝脏PGC‐1α蛋白及基因表达水平均有所降低，但单纯促动脉粥样硬化饮食组大鼠肝脏PGC‐1α蛋白及基因表达水平明显低于利拉鲁肽干预组（ P＜0.05），且低剂量干预组低于高剂量干预组。结论利拉鲁肽对促动脉粥样硬化饮食喂养大鼠的大血管有一定保护作用，并呈一定剂量依赖性，其机制可能与促进肝脏PGC‐1α的表达有关。