anti-MYPT1, anti-JNK, and anti-TGFβ1 湖北医科大学(英文版).pdfVIP

Acta Pharmacologica Sinica (2011) 32: 999–1008 npg © 2011 CPS and SIMM All rights reserved 1671-4083/11 $32.00 /aps Original Article Involvement of RhoA/ROCK in myocardial fibrosis in a rat model of type 2 diabetes 1 2, * 1 1 2 1 1 Hong ZHOU , Yong-jun LI , Mian WANG , Li-hui ZHANG , Bing-yan GUO , Zhan-sheng ZHAO , Feng-ling MENG , 1 1 Yong-gui DENG , Rui-ying WANG Department of 1Endocrinology and 2Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China Aim: To investigate whether activation of RhoA/Rho kinase (ROCK) is involved in myocardial fibrosis in diabetic hearts. Methods: A rat model of type 2 diabetes was established using high fat diet combined with streptozotocin (30 mg/kg, ip). Animals were randomly divided into 3 groups: control rats, untreated diabetic rats that received vehicle and treated diabetic rats that received Rho- -1 -1 kinase inhibitor fasudil hydrochloride hydrate (10 mg·kg ·d , ip, for 14 weeks). Cardiac contractile function was evaluated in vivo. The morphological features of cardiac fibrosis were observed using immunohistochemistry and TEM. The mRNA expression of JNK, TGFβ1, type-I, and type-III procollagen was assessed with RT-PCR. The phosphorylation of MYPT1, JNK and Smad2/3, as well as the protein levels of TGFβ1 and c-Jun, were evaluated using Western blotting. Results: In untreated diabetic rats, myocardial fibrosis was developed and the heart contractility was significantly redu