利拉鲁肽下调糖尿病ApoE^-/-小鼠主动脉糖基化终产物受体表达并减轻动脉粥样硬化

Liraglutide alleviates arteriosclerotic lesions and inhibits receptor for advanced glycation end-productexpression in diabetic ApoE^-/- mice

目的观察利拉鲁肽干预能否调节糖尿病ApoE基因敲除（ApoE^-/-）小鼠主动脉糖基化终产物受体（RAGE）的表达，进而影响动脉粥样硬化病变程度。方法30只雄性ApoE“小鼠分为3组：对照组、糖尿病组和糖尿病＋利拉鲁肽组。所有小鼠高脂饲料喂养。链脲佐菌素（STZ，55mg·kg^-1·d^-1）腹腔注射连续两天制备糖尿病，利拉鲁肽组皮下注射利拉鲁肽（0．4mg·kg^-1d^-1）。9周后，取血测定糖基化终产物（AGEs）、可溶性糖基化终产物受体（sRAGE）、基质细胞衍生因子lct（SDF．1α）、总胆固醇、三酰甘油水平，并取完整主动脉测定RAGE的表达，使用苏丹Ⅳ染色评估主动脉粥样硬化面积。结果与对照组相比，糖尿病组小鼠血清AGEs水平明显升高，主动脉RAGE表达明显升高，斑块总面积明显增加；与糖尿病组小鼠比较，糖尿病＋利拉鲁肽组小鼠血清AGEs水平明显下降，SDF-1α水平明显升高，主动脉RAGE表达明显下降，斑块总面积明显减少。结论利拉鲁肽下调糖尿病ApoE^-/-小鼠主动脉RAGE表达，并减轻动脉粥样硬化病变程度。

Objective To observe the effect of liraglutide on arteriosclerotic lesions in diabetic ApoE^-/- mice via regulating receptor for advanced glycation end-products （RAGE） expression of aorta. Methods Thirty male ApoE^-/- mice （10 weeks） were randomly divided into 3 groups： control group, diabetes group, and diabetes＋ liraglutide group. All the mice were fed a high-fat diet. Diabetes was induced by 2 intraperitoneal injection of streptozotocin （ STZ, 55 mg· kg^-1 · d^-1）. Mice were treated with subcutaneous injection of liraglutide （0.4 mg · kg^-1 · d^-1 ） in diabetes＋liraglutide group. After 9 weeks, blood was drawn and the aorta were rapidly procured. The serum levels of advanced glycation end-products （ AGEs）, soluble receptor for advanced glycation end-products （sRAGE）, stromal cell-derived factor-lot （SDF-lα）, as well as total cholesterol and triacylglycerol were measured. Atherosclerotic plaque area was determined by Sudan IV staining. The expression of RAGE was determined using RT-PCR and western blot, respectively. Results Compared with control group, the serum AGEs, the RAGE protein and mRNA expression, the atherosclerotic lesions were significantly increased in the mice of diabetes group. Compared with diabetes group, the serum AGEs, the RAGE protein and mRNA expression, the atherosclerotic lesions were significantly decreased in the mice of diabetes＋liraglutide group. Conclusion Liraglutide is confirmed as to have an anti-atherosclerotic effects and inhibits RAGE expression in diabetic ApoE^-/- mice.