Influence of a new endothelin receptor antagonist CPU-0213 on expression of MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin

Abstract

Abstract: AIM: To observe the alterations of matrix metalloproteinases (MMPs) and TIMPs (the inhibitor of MMPs) and to study the influence of a new endothelin receptor antagonist CPU-0213 on MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin (L-thy).METHODS: Male Sprague-Dawley rats were randomly divided into three groups and sc administrated suspension of L-thy (0.4 mg·kg ^-1·d ^-1) for consecutive 10 d except for normal group.On the 7th day, the rats treated with L-thy were given CPU-0213 (ig, 100 mg · kg ^-1·d ^-1) for 3 d.The whole collagen content in myocardium was measured.Relative LV myocardial mRNA levels of MMPs (MMP-2, MMP-9) and tissue inhibitor (TIMP-1, TIMP-2) were detected with semi-quantitative RT-PCR.RESUITS: The whole collagen content in myocardium induced by L-thy decreased but it increased in the group CPU-0213.The expression of MMPs (MMP-2, MMP-9) mRNA was downregulated in L-thy group and the expression of TIMPs mRNA was upregulated in L-thy group markedly.Treated with CPU-0213, the expressions of MMP-9 and TIMP-1 mRNA were downregulated, whereas the expression of MMP-2 mRNA coming from CPU-0213 group tended to upregulate.But there was no statistical significance among these groups. CONCLUSION: CPU-0213 can inhibit the expression of MMPs and increase collagen content, which can improve heart function.

Key words: L-thyroxin, metalloproteinases, TIMPs, RT-PCR, CPU-0213

CLC Number:

R965.1

LIU Qing, DAI De-Zai. Influence of a new endothelin receptor antagonist CPU-0213 on expression of MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 281-284.

References

1 Chapman D, Weber KT, Eghbali M.Regulation of fibrillar collagen type Ⅰ and Ⅲ and basement membrane type Ⅳ collagen gene expression in pressure overloaded rat myocardium[J].Cir Res, 1990;67(4):787-94
2 Peterson JT, Hallak H, Johnson L, Li H, O'Brien PM, Sliskovic DR, et al.Matrix metalloproteinase inhibition attenuatates left ventricular remodeling and dysfunction in a rat model of progressive heart failure[J].Circulation, 2001;103(8):2303-9
3 Stetler-Stevenson WG.Dynamics of matrix turnover during pathologic remodeling of the extracellular matrix [J].Am J Pathol, 1996;148(5):1345-50
4 David E, Kleiner, William G.Stetler-stevenson Quantitative zymography:detection of gram quantities of gelatinases[J].Anal Biochem, 1994;218(1):325-9
5 Grant MB, Caballero S, Tarnuzzer RW, Bass KE, Ljubimov AV, Spoerri PE, et al.Matrix metalloproteinase expression in human retinal microvascular cells[J].Diabetes, 1998;47(8): 1311-7
6 Tang M, Potter JJ, Mezey E.Leptin enhances the effect of transforming growth factor beta in increasing type I collagen formation[J].Biochem Biophys Res Commun, 2002;297(2):906-16
7 Tyagi SC, Matsubara L, Weber KT.Direct extraction and estimation of collagenase (s) activity by zymography in micro-quantities of rat myocardium and uterus[J].Clini Biochem, 1993;26 (3):191-8
8 Cheung PY, Sawicki G, Wozniak W, Wang WJ, Raadoinski MW, Schulz R, et al.Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart[J].Circulation, 2000; 101(8):1833-9
9 Polikar R, Burger AG, Scherrer U, Nicod P.The thyroid and heart[J].Circulation, 1993;87(5):1435-41
10 Dai ZD, Wang HN, Zhang GQ, He GX, Li C.Matrix is the site of indirect effects of propranolol on the ion channelopathies in cardiac remodeling by L-thyroxine[J].J Car Surg, 2002;17 (6):439-46
11 Wu XD, Dai DZ.Effect of propranolol and verapamil on mRNA expression of cardiac Ryanodine receptor-2 and SERCA in hypertrophied rat induced by L-thyroxin[J].Act Pharmacol Sin, 2004;25(in press)
12 张广钦, 马玉萍, 郝雪梅, 周培爱, 吴才宏, 戴德哉.甲状腺素诱导的豚鼠肥厚心肌中延迟整流钾电流离子通道特征[J].中国药理学通报, 2001;17(2):11-4
13 戴德哉, 胡慧娟, 杨平, 马玉萍, 曹文, 王红兰.离子通道病变与心肌重构的致心律失常性[J].中国病理生理学杂志, 2000;16(10):945-7
14 Dai DZ.Vulnerable substrate and multiple ion channel disorder in a diseased heart will be new targets for antiarrhythmic therapy [J].Act Pharmacol Sin, 2000;21(4):289-95
15 梁黔生.左心肥厚的研究近况[J].心血管病学进展,2001;22(3):143-6

[1]	CHENG Yuan-guang, WU Pei. Expression of somatostatin receptor type 2 in colorectal cancer [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(10): 1100-1104.
[2]	SHI Liang-hui, ZHANG Cai-quan, PENG Xiao-zhuang. Relationship between the expression of LAT1,CD98hc and clinical pathological characteristics of gastric carcinoma [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1361-1366.
[3]	ZHONG Yong-jun, CHEN Dong-qin, YAO Xiao-yan. Study of autocamtide 2-related inhibitory peptide prevent cardiac fibroblasts excreting cytokines and expressing matrix metalloproteinases [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(4): 422-428.
[4]	HUANG Lai-quan, WEI Zhong-lin, ZHANG Jun, ZHANG Dai-yun, WANG Xing-hong. Expressions of BAG-1 and NF-κB P65 in the mononuclearcell of multiplemyeloma patients [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(3): 292-297.
[5]	LIU Ya-li, ZHANG Li, JIN Hai-yan, AN Shu-hua. Effects of metalloproteinases-9 and tissue inhibitor of metalloproteinase on airway remodeling and the intervention effect of anti-RANTES antibody in rats with asthma [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(9): 985-990.
[6]	ZHANG Zheng-shou, JIANG Han-dong, WANG Li-na. Inhibition of Okam extract J201 on bleomycin induced pulmonary fibrosis in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(3): 304-307.
[7]	QI Min-you, XIA Hui-jing, DAI De-zai, TANG Xiao-yun, SU Wei, ZHANG Can. CPU86017 and its enantiomers inhibit abnormal gene expression of calcineurin and NFκB in rat cardiomyopathy induced by L-thyroxin [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(4): 392-397.
[8]	LI Yun-man, KANG Kai, FANG Wei-rong. Lomerizine inhibits activity of P-glycoprotein in primary cultured brain microvessel endothelial cell monolayers [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(10): 1110-1114.
[9]	LIANG Xu-guo, ZHANG Xiu-mei. Effect of combination of ACEI and ARB on left ventricle in pressure-overloaded hypertrophy rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(10): 1133-1136.
[10]	YU Hong-e, YU Qing-sheng, LIU Xin-yan, ZHU Liu, LOU Xiao-hua, TENG Mai-kun. China cobra venom active factor (CCVAF) inhibits VEGF and bFGF in lung cancer cell line H1299 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(9): 970-973.
[11]	WU Jia-bin, XU Chun-xuan, ZHANG Jian-cheng, CHEN Lin, LIN Li-fang, HU Xi-zhong. Study of chloride channel ClC-3 gene expression in patient with atrial fibrillation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(6): 651-654.
[12]	FENG Zheng-quan, SHEN Min-he, WU Liang-cun. Research of regulating Bccap-37 cell treated with baicalin on TIMP2 expression in vitro [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(6): 705-708.
[13]	LU Zhi-hong, XIONG Xiao-yun, MENG Jing-ru, LIU Zhen-guo, WANG Zhi-peng, MEI Qi-bing. Changes of three COX isoforms expression after formalin induced inflammatory pain in brain and analgesic effects of different COX inhibitors [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(5): 499-504.
[14]	LIN Qiu-xiong, SHAN Zhi-xin, YU Xi-yong, Yang Ming, LIN Shu-guang, Hui-yao LAN. Effects of different lipid on MIF mRNA and protein expression in cultural macrophage [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(3): 329-332.
[15]	HUANG Yi-xing, CHEN Liao-bin, WANG Hui, YI Xian-hong, WANG Peng. Experimental study on the effects of dehydroepiandrosterone on osteoarthritis in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(10): 1181-1185.