Cardiac Fibrosis in Diabetic Rats: Regulation and Mechanism of Activation of the PPARγ Signal Pathway

Shu-Mei Zhao ； Hong-Wei Li ； Chun-Yan Guo ； Lu-Hua Shen

《The Chinese Journal of Physiology》 53卷4期 (2010/08) Pp. 262-267

https://doi.org/10.4077/CJP.2010.AMK076

並列摘要

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a member of the nuclear hormone receptor superfamily which affects organic fibrosis. The aims of the study were to approach the effects of activation of the PPARγ signal pathway on cardiac fibrosis in diabetic rats, and also the effects on cardiac remodeling and function. Type 1 diabetic models were used in the study. All the animals were divided into 3 groups: I: control group; II: diabetic group; III: diabetes+Pioglitazone (Piog, a PPARγ ligand) administration group. After 14 weeks of feeding, general condition, fibrosis indices, echocardiography and interventricular pressures parameters were detected. At the 14th week, compared with group I, the hydroxyproline concentration in group II significantly increased, and CO I and III distribution was more obvious by sirius red staining. Reduction of LVSP (left ventricular systolic pressure) and increase of LVEDP (left ventricular end-diastolic pressure) were also significant in group II. But these situations were changed by the administration of Piog in group III. Furthermore, results of RT-PCR and immunohistochemistry showed that Piog administration reduced angiotensin II type 1 receptor (AT1-R) expression in diabetic models. Hence, activation of the PPARγ signal pathway could repress cardiac fibrosis in diabetic rats, and partly improve cardiac remodeling and function by downregulating activity of RAS at the receptor level.

並列關鍵字

PPARγ signal pathway ； cardiac fibrosis ； angiotensin II type 1 receptor AT1-R ； diabetes

參考文獻

Bastos, E. L.,Fagundes, D. J.,Taha, M. O.,Novo, N. F.,Juliano, Y.,Simões, Mde, J.,Silvado, R. A.(2006).The role of bovine preserved peritoneum in rats ventral hernia: a histological evaluation.Acta Cir. Bras..21,328-331.

Jin, D.,Takai, S.,Sugiyama, T.,Hayashi, T.,Fukumoto, M.,Oku, H.,Kitaura, Y.,Ikeda, T.,Miyazaki, M.(2009).Long-term angiotensin II blockade may improve not only hyperglycemia but also ageassociated cardiac fibrosis.J Pharmacol. Sci..109,275-284.

Marx, N.,Walcher, D.,Ivanova, N.,Rautzenberg, K.,Jung, A.,Friedl, R.,Hombach, V.,de, Caterina, R.,Basta, G.,Wautier, M. P.,Wautiers, J. L.(2004).Thiazolidinediones reduce endothelial expression of receptor for advanced glycation end products.Diabetes.53,2662-2668.

McCalmon, S. A.,Desjardins, D. M.,Ahmad, S.,Davidoff, K. S.,Snyder, C. M.,Sato, K.,Ohashi, K.,Kielbasa, O. M.,Mathew, M.,Ewen, E. P.,Walsh, K.,Gavras, H.,Naya, F. J.(2010).Modulation of angiotensin II-mediated cardiac remodeling by the MEF2A target gene xirp2.Circ. Res..

Min, Q.,Bai, Y. T.,Jia, G.,Wu, J.,Xiang, J. Z.(2010).High glucose enhances angiotensin-II-mediated peroxisome proliferationactivated receptor-γ inactivation in human coronary artery endothelial cells.Exp. Mol. Pathol..88,133-137.