摘要
Background Although the insulinotropic role of glucagon-like peptide-1 （GLP-1） in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. This study aimed to determine the effects of GLP-1 on injury of rats cardiac myocytes induced by hypoxia-reoxygenation （H/R） and the possible mechanisms. Methods The cultured neonatal rats cardiac myocytes were randomly divided into seven groups： the normal control group, the H/R group, the GLP-1＋H/R group, the GLP-1＋H/R＋UO126 （the p42/44 mitogen-activated protein kinase （MAPK） inhibitor） group, the GLP-1＋H/R＋LY294002 （phosphatidylinositol 3-kinase （PI3K） inhibitor） group, the H/R＋UO126 group, and the H/R＋LY294002 group. The lactate dehydrogenase （LDH） activity, apoptosis rate of cardiac myocytes, and caspase-3 activity were detected after the injury of H/R. Results Compared with the normal control group, the activity of LDH, cardiac myocyte apoptosis rate, and caspase-3 activity all increased significantly in the H/R group （P 〈0.01）. Compared with the H/R group, these three indices all decreased in the H/R＋GLP-1 group （P 〈0.01）. However, the changes of LDH activity, apoptosis rate, and caspase-3 activity were inhibited by LY294002 and UO126 respectively. Conclusions GLP-1 can directly act on cardiac myocytes and protect them from H/R injury mainly by inhibiting their apoptosis. Its mechanism may be through the PI3K-Akt pathway and the MAPK signaling pathway.
Background Although the insulinotropic role of glucagon-like peptide-1 （GLP-1） in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. This study aimed to determine the effects of GLP-1 on injury of rats cardiac myocytes induced by hypoxia-reoxygenation （H/R） and the possible mechanisms. Methods The cultured neonatal rats cardiac myocytes were randomly divided into seven groups： the normal control group, the H/R group, the GLP-1＋H/R group, the GLP-1＋H/R＋UO126 （the p42/44 mitogen-activated protein kinase （MAPK） inhibitor） group, the GLP-1＋H/R＋LY294002 （phosphatidylinositol 3-kinase （PI3K） inhibitor） group, the H/R＋UO126 group, and the H/R＋LY294002 group. The lactate dehydrogenase （LDH） activity, apoptosis rate of cardiac myocytes, and caspase-3 activity were detected after the injury of H/R. Results Compared with the normal control group, the activity of LDH, cardiac myocyte apoptosis rate, and caspase-3 activity all increased significantly in the H/R group （P 〈0.01）. Compared with the H/R group, these three indices all decreased in the H/R＋GLP-1 group （P 〈0.01）. However, the changes of LDH activity, apoptosis rate, and caspase-3 activity were inhibited by LY294002 and UO126 respectively. Conclusions GLP-1 can directly act on cardiac myocytes and protect them from H/R injury mainly by inhibiting their apoptosis. Its mechanism may be through the PI3K-Akt pathway and the MAPK signaling pathway.
