Effects of urocortin on mitochondria-dependent apoptotic pathway in ischemia rats

AIM: To investigate the effects of urocortin (UCN) on mitochondria-dependent apoptotic pathway. METHODS: Twenty four Wistar rats were randomly divided into three groups (n=8): control group (CON), ischemia/reperfusion (I/R) group and UCN group. The left ventricular samples in CON group were collected as pre-ischemia control through thoracotomy. After isolated heart Langendoff and Neely models were established, rat hearts in I/R group and UCN group were continuously perfused with Krebs-Henseleit (K-H) buffer solution for 30 min and then the rat hearts were arrested by cardioplegia, St.Thomas-2 solution (STH-2) for 30 min. Rat hearts in I/R group were reperfused with K-H buffer solution for 90 min and rat hearts in UCN group were reperfused with K-H buffer solution containing 10-8 mol/L urocortin for 90 min. Release of cytochrome C (Cyto C) protein into the cytosol was detected by Western blot. The expressions of Bcl-2 and caspase-3 protein were detected by immunohistochemical assay in cardiomyocyte, and the apoptosis index (AI) of cardiomyocyte was detected by TUNEL. RESULTS: Compared with that in CON group, expression of Bcl-2, caspase-3 and Cyto c protein in I/R and UCN groups significantly increased (P<0.05). Bcl-2 protein expression in UCN group was higher than in I/R group (0.2±0.05 vs.0.12±0.06, P<0.05). Expression of caspase-3 and Cyto C protein in UCN group was lower than in I/R group (0.24±0.70 vs.0.36±0.15, P<0.05, 0.88±0.07 vs.1.29±0.02, P<0.05). After reperfusion, AI in I/R group and UCN group was significantly higher than in CON group (P<0.05). Compared with I/R group, AI in UCN group increased (6.77±1.12 vs.12.81±0.62, P<0.05). CONCLUSION: UCN protects hearts against I/R injury through interfering with mitochondria-dependent apoptotic pathway.