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标题：Gαq-Protein Carboxyl Terminus Imitation Polypeptide (GCIP)-27 Inhibits Right Ventricular Hypertrophy Induced by Monocrotaline in Rats
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作者：Dan-Li Yang ; Hai-Gang Zhang ; Ya-Li Xu 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：3
页码：376-381
DOI：10.1248/bpb.32.376
出版社：The Pharmaceutical Society of Japan
摘要：This study was to investigate the probable inhibitory effect of Gαq-protein carboxyl terminus imitation polypeptide-27 (GCIP-27), the optimized form of GCIP, which is a competition candidate of the activated binding sites on Gαq, on the right ventricular (RV) hypertrophy induced by monocrotaline (MCT) in rats. We have previously shown that GCIP-27, can prevent the hypertrophyc responses in cultured rat cardiomyocytes induced by noradrenaline and angiotensin II. Male Sprague-Dawley rats were given a single dose (50 mg/kg) of MCT subcutaneouly to induce pulmonary hypertension (PH) and RV hypertrophy. GCIP-27 (30, 90 μg/kg) or vehicle was administered (twice daily, intraperitoneally) from day 1 to day 21. GCIP-27 (90 μg/kg) inhibited the elevated pulmonary arteria systolic pressure (PASP) and mean pulmonary arteria pressure induced by MCT, but its dose at 30 μg/kg only reduced the elevated PASP. And no effect could be seen on the pulmonary arteria diastolic pressure at both two doses. On the other hand, the two doses of GCIP-27 improved significantly the weight ratio of RV to left ventricle plus septum, the RV free wall thickness and pulmonary arteria acceleration time (PAAT). In morphometric observation, GCIP-27 (30, 90g/kg) could attenuate cardiomyocytes hypertrophy, interstitium fibrosis, mitochondria swelling and malformation markedly in RVs of MCT-treated rats. Furthermore, GCIP-27 (30, 90 μg/kg) significantly reduced the overexpression of the proliferating cell nuclear antigen (PCNA) induced by MCT in RV cardiocytes. The results suggest that GCIP-27 can effectively attenuate the RV hypertrophy induced by MCT in rats, which may be mediated by both the direct effect on cardiomyocyte and the secondary effect by reducing PH, and may be involved in its influence on the Gq signal pathway.
关键词：right ventricular hypertrophy;G protein;polypeptide drug;monocrotaline