[Effects of propofol on PI3K/Akt signaling pathway and endoplasmic reticulum stress pathway of apoptosis induced by ischemia-reperfusion in isolated rat hearts].

OBJECTIVE: To explore the effects of propofol on the PI3K/Akt signaling pathway and the endoplasmic reticulum stress pathway of apoptosis induced by ischemia-reperfusion in isolated rat hearts. METHODS: Forty isolated rat hearts were completely randomly assigned into 5 different groups: control (C), ischemia/reperfusion (I/R), propofol (P), propofol plus Wortmannin (P + Wort) and Wortmannin (W). The isolated hearts were perfused on a Langendorff apparatus. Except for group C, all hearts were subjected to 30 min global ischemia and 120 min reperfusion. In the P, P + W and W groups, 50 µmol/L propofol or 50 µmol/L propofol + 100 nmol/L Wortmannin or 100 nmol/L Wortmannin were respectively added in the K-H buffer to perfuse for 10 min at pre-ischemia and 20 min at the beginning of reperfusion. The parameters of cardiac function were recorded at pre-ischemia and at the 120 min of reperfusion. The apoptotic index was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel). The expressions of caspase-12 and CCAAT/C/EBP homologous protein (chop) were measured by immunohistochemistry while those of Akt and p-Akt (Ser473) detected by Western blot. RESULTS: Compared with the I/R group, LVEDP significantly deceased and +dp/dtmax significantly increased, the apoptotic index [(27.89 ± 1.04)% vs (33.70 ± 2.20)%], the expressions of caspase-12 [(0.1728 ± 0.0096) vs (0.2332 ± 0.0114)] and chop [(0.1889 ± 0.0078) vs (0.2407 ± 0.0123)] significantly deceased while that of p-Akt (Ser473) significantly increased in Group P (P < 0.05). Wortmannin abolished the partial protective effects of propofol postconditioning (P < 0.05). CONCLUSION: Propofol perfusion may attenuate the endoplasmic reticulum stress pathway of apoptosis induced by ischemia/reperfusion in isolated rat hearts partly through the PI3K/Akt signal pathway.