Calcitonin gene-related peptide inhibits anoxia/reoxygenation-induced increases in the enzymatic activity of caspase-3 and caspase-9 through the protein kinase C-mitochondrial ATP sensitive potassium channel pathway

Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the apoptosis of rat cardiomyocytes induced by anoxia/reoxygenation (A/R) and its related signaling pathways. Methods A total of 60 male healthy SD rats aging 1 d to 3 d were selected to establish a primary model of cardiomyocytes in vitro. The animals were randomly divided ten groups before A/R experiments (n=6): ① a control group, ② an A/R group, ③ a CGRP+A/R group, ④ a CGRP8-37+CGRP+A/R group, ⑤ an 5-HD+CGRP+A/R group, ⑥ a DZ+A/R group, ⑦ an H-89+CGRP+A/R group, ⑧ a chelerythine+CGRP+A/R group, ⑨ a glibenclamide+CGRP+A/R group and ⑩ an HMR-1098+CGRP+A/R group. The activities of caspase-3 and caspase-9 were measured by spectrophotometry. Results Compared with the control group, the A/R group showed significantly increased activities of caspase-3 and caspase-9 (P 0.05). Compared with the CGRP+A/R group, the chelerythine+CGRP+A/R group produced significantly increased activities of caspase-3 and caspase-9 (P 0.05). Conclusions CGRP relieves cardiomyocyte A/R injury and plays an important role in cardiomyocyte apoptosis by activating protein kinase C-mitochondrial ATP sensitive potassium channel and decreasing the expression of caspase-3 and caspase-9. Key words: Calcitonin gene-related peptide; Anoxia-reoxygenation injury; ATP sensitive potassium channel; Caspases; Cardiomyocytes