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英文论文.pdfVIP

Hindawi Publishing Corporation Experimental Diabetes Research Volume 2012, Article ID 146194, 10 pages doi:10.1155/2012/146194 Research Article 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 Min Shen, Dongdong Sun, Weijie Li, Bing Liu, Shenxu Wang, Zheng Zhang, and Feng Cao Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China Correspondence should be addressed to Dongdong Sun, wintersun3@ and Feng Cao, wind8828@ Received 20 September 2011; Revised 19 November 2011; Accepted 22 November 2011 Academic Editor: Daisuke Koya Copyright © 2012 Min Shen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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