Hydrogen sulfide suppresses the expression of MMP-8, MMP-13, and TIMP-1 in left ventricles of rats with cardiac volume overload  

作　　者：Chao-ying ZHANG Xiao-hui LI Ting ZHANG Jin FU Xiao-dai CUI 

机构地区：[1]Department of Cardiovascular Diseases, Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing 100020, China [2]Central Laboratory of Infection and Immunity, Capital Institute of Pediatrics, Beijing 100020, China [3]Central Laboratory for Clinical Research, Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing 100020, China

出　　处：《Acta Pharmacologica Sinica》2013年第10期1301-1309,共9页中国药理学报（英文版）

基　　金：The work was supported by the National Natural Science Foundation of China （No 30872787）, Beijing Outstanding Talents Training Program （20081D0303200107） and Science Foundation for High-Level Medical Talents of Beijing Health System （2011-3-067）.

摘　　要：Aim： To study the effects of hydrogen sulfide （H2S） on the left ventricular expression of MMP-8, MMP-13, and TIMP-1 in a rat model of congenital heart disease. Methods： Male SD rats underwent abdominal aorta-inferior vena cava shunt operation. H2S donor NariS （56 μmol.kg-1.d-1, ip） was injected from the next day for 8 weeks. At 8 weeks, the hemodynamic parameters, including the left ventricular systolic pressure （LVSP）, the left ventricular peak rate of contraction and relaxation （LV＋dp/dtmax） and the left ventricular end diastolic pressure （LVEDP） were measured. The left ventricular tissues were dissected out, and hydroxyproline and collagen I contents were detected with ELISA. The expression of MMP-8, MMP-13, and a tissue inhibitor of metalloproteinase-1 （TIMP-1） in the tissues was measured using real-time PCR, Western blotting, and immunohistochemistry, respectively. Results： The shunt operation markedly reduced LVSP and LV＋dp/dtmax, increased LVEDP, hydroxyproline and collagen I contents, as well as the mRNA and protein levels of MMP-8, MMP-13, and TIMP-1 in the left ventricles. Chronic treatment of the shunt operation rats with NariS effectively prevented the abnormalities in the hemodynamic parameters, hydroxyproline and collagen I contents, and the mRNA and protein levels of MMP-13 and TIMP-1 in the left ventricles. NariS also prevented the increase of MMP-8 protein expres- sion, but did not affect the increase of mRNA level of MMP-8 in the shunt operation rats. Conclusion： H2S suppresses protein and mRNA expression of MMP-8, MMP-13, and TIMP-1 in rats with cardiac volume overload, which may be contributed to the amelioration of ventricular structural remodeling and cardiac function.Aim： To study the effects of hydrogen sulfide （H2S） on the left ventricular expression of MMP-8, MMP-13, and TIMP-1 in a rat model of congenital heart disease. Methods： Male SD rats underwent abdominal aorta-inferior vena cava shunt operation. H2S donor NariS （56 μmol.kg-1.d-1, ip） was injected from the next day for 8 weeks. At 8 weeks, the hemodynamic parameters, including the left ventricular systolic pressure （LVSP）, the left ventricular peak rate of contraction and relaxation （LV＋dp/dtmax） and the left ventricular end diastolic pressure （LVEDP） were measured. The left ventricular tissues were dissected out, and hydroxyproline and collagen I contents were detected with ELISA. The expression of MMP-8, MMP-13, and a tissue inhibitor of metalloproteinase-1 （TIMP-1） in the tissues was measured using real-time PCR, Western blotting, and immunohistochemistry, respectively. Results： The shunt operation markedly reduced LVSP and LV＋dp/dtmax, increased LVEDP, hydroxyproline and collagen I contents, as well as the mRNA and protein levels of MMP-8, MMP-13, and TIMP-1 in the left ventricles. Chronic treatment of the shunt operation rats with NariS effectively prevented the abnormalities in the hemodynamic parameters, hydroxyproline and collagen I contents, and the mRNA and protein levels of MMP-13 and TIMP-1 in the left ventricles. NariS also prevented the increase of MMP-8 protein expres- sion, but did not affect the increase of mRNA level of MMP-8 in the shunt operation rats. Conclusion： H2S suppresses protein and mRNA expression of MMP-8, MMP-13, and TIMP-1 in rats with cardiac volume overload, which may be contributed to the amelioration of ventricular structural remodeling and cardiac function.

关 键 词：congenital heart disease cardiac volume overload hydrogen sulfide MMP-8 MMP-13 tissue inhibitor of metalloproteinase1 HYDROXYPROLINE collagen I ventricular remodeling 

分 类 号：Q492.6[生物学—生理学] S858.966[农业科学—临床兽医学]