缬沙坦与LAF237 [(S)-1-[(3-羟基-1-金刚烷基)弹药]乙酰-2-氰吡啶]对2型糖尿病小鼠血管氧化应激和炎症的协同作用。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-03-15 DOI:10.1155/2012/146194
Min Shen, Dongdong Sun, Weijie Li, Bing Liu, Shenxu Wang, Zheng Zhang, Feng Cao
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引用次数: 11

摘要

目的:探讨缬沙坦(血管紧张素II型1受体阻断剂)与LAF237 (DPP-IV抑制剂)联合应用对db/db小鼠主动脉氧化应激和炎症损伤的预防作用及机制。方法:40只Db/ Db小鼠随机接受缬沙坦、LAF237、缬沙坦+ LAF237或生理盐水治疗。观察糖尿病小鼠主动脉氧化应激和炎症反应。结果:缬沙坦或LAF237预处理可显著提高糖尿病小鼠主动脉内皮细胞GLP-1的表达,减少其凋亡。NAD(P)H氧化酶亚基的表达也显著降低,导致超氧化物生成和ICAM-1减少(倍数变化:缬沙坦:7.5±0.7,P < 0.05;LAF237: 10.2±1.7,P < 0.05), VCAM-1(折叠变化:缬沙坦:5.2±1.2,P < 0.05;LAF237: 4.8±0.6,P < 0.05), MCP-1(折叠变化:缬沙坦:3.2±0.6,LAF237: 4.7±0.8;P < 0.05)表达。缬沙坦与LAF237联合治疗GLP-1表达升高更为显著。血管氧化应激和炎症反应的降低也高于缬沙坦或LAF237单药治疗。结论:LAF237联合缬沙坦对2型糖尿病小鼠血管氧化应激和炎症有协同作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] on vascular oxidative stress and inflammation in type 2 diabetic mice.

Aim: To investigate the combination effects and mechanisms of valsartan (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on prevention against oxidative stress and inflammation injury in db/db mice aorta.

Methods: Db/db mice (n = 40) were randomized to receive valsartan, LAF237, valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in diabetic mice aorta were examined.

Results: Valsartan or LAF237 pretreatment significantly increased plasma GLP-1 expression, reduced apoptosis of endothelial cells isolated from diabetic mice aorta. The expression of NAD(P)H oxidase subunits also significantly decreased resulting in decreased superoxide production and ICAM-1 (fold change: valsartan : 7.5 ± 0.7, P < 0.05; LAF237: 10.2 ± 1.7, P < 0.05), VCAM-1 (fold change: valsartan : 5.2 ± 1.2, P < 0.05; LAF237: 4.8 ± 0.6, P < 0.05), and MCP-1 (fold change: valsartan: 3.2 ± 0.6, LAF237: 4.7 ± 0.8; P < 0.05) expression. Moreover, the combination treatment with valsartan and LAF237 resulted in a more significant increase of GLP-1 expression. The decrease of the vascular oxidative stress and inflammation reaction was also higher than monotherapy with valsartan or LAF237.

Conclusion: These data indicated that combination treatment with LAF237 and valsartan acts in a synergistic manner on vascular oxidative stress and inflammation in type 2 diabetic mice.

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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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