| ObjectiveTo investigate the protective effect of propofol onischemia-reperfusion injury in isolated rat hearts, to determine if propofolattenuate the endoplasmic reticulum stress pathway of apoptosis induced byischemia-reperfusion in isolated rat hearts and the role of PI3K/Aktsignaling pathway.MethodsForty isolated rat hearts were completely randomly assigned to5different groups: control group(C), ischemia/reperfusion group (I/R),propofol group (P), propofol+Wortmannin group (P+Wort) andWortmannin group (W). The isolated rat hearts were perfused on aLangendorff apparatus with Kerbs-Henseleit buffer (KHB). Except for Cgroup, all the hearts were subjected to30min global ischemia and followedby120min reperfusion. (1) C Group: rat hearts were continuously perfused with KHB for180min.(2) I/R Group: after30min perfusion with KHB, the rat hearts weresubjected to30min global ischemia and120min reperfusion.(3) P Group:after20min stabilized perfusion with KHB, the rat hearts were perfusedwith KHB contained50μmol/Lpropofol for10min preischemia and for20min at the beginning of reperfusion, the other with the same of I/R group.(4) P+Wort group: after20min stabilized perfusion with KHB, the rathearts were perfused with KHB contained50μmol/L propofol plus100nmol/L propofol for10min before ischemia and for20min at thebeginning of reperfusion, the other with the same of I/R group.(5) Wortgroup: after20min stabilized perfusion with KHB, the rat hearts wereperfused with KHB contained100nmol/L propofol for10min beforeischemia and for20min at the beginning of reperfusion, the other with thesame of I/R group. The cardiac function indexes such as the left ventricularend-diastolic pressure (LVEDP), maximum rates of left ventricular pressuredevelopment and decay (±dp/dtmax) were measured before ischemia and atthe120min of reperfusion. The cTnI concentration in coronary effluentwas measured by ELISA. The apoptotic index was measured by terminaldeoxynucleotidyl transfease-mediated dUTP nick end labeling (TUNEL)method. The expressions of caspase-12and chop were measured byimmunohistochemistry. The expressions of Akt and p-Akt（Ser473）weremeasured by Western blot. Results1. The effect of propofol on the hemodynamic parametersThe hemodynamic parameters were no significant difference beforeischemia in each group (P>0.05). Compared with group C,+dp/dtmaxweredecreased significantly, LVEDP were significantly increased in othergroups (P<0.05). Compared with I/R group, the+dp/dtmaxwere increased,LVEDP were lower In P group (P <0.05). Compared with P group, theWortmannin partly abolished the effect to improve the hemodynamicparameters of the postischemic rat hearts (P <0.05). There were nosignificant difference between I/R group and Wort group.2. The effect of propofol on the cTnI concentrationCompared with group C, the cTnI concentration were significantlyincreased in other groups (P<0.05). Compared with I/R group, the cTnIconcentration was lower in group P (P<0.05). Compared with P group, theWortmannin partly abolished the effect of propofol to decrease cTnIconcentration in coronary effluent of the postischemic rat hearts (P <0.05).There were no significant difference between I/R group and Wort group.3. The effect of propofol on the apoptotic indexCompared with C group, there were significantly increased incardiomyocytes apoptosis in other groups (P<0.05). Compared with groupI/R, the AI was lower in group P (P<0.05). Compared with P group, theWortmannin partly abolished the protective effect in the postischemic rat hearts induced by propofol (P <0.05). There were no significant differencebetween I/R group and Wort group.4. The effect of propofol on the expressions of caspase-12and chopCompared with C group, the expressions of caspase-12and chopwere significantly increased in other groups (P<0.05). Compared withgroup I/R, the expressions of caspase-12and chop were lower in group P(P<0.05). Compared with P group, the Wortmannin partly abolished theeffect of decreasing the expressions of caspase-12and chop in thepostischemic rat hearts induced by propofol (P <0.05). There were nosignificant difference between the I/R group and Wort group.5. The effect of propofol on the expressions of Akt and p-AktThe expressions of Akt were no significant difference in each group(P>0.05). Compared with group I/R, the expressions of p-Akt weresignificantly increased in group P (P<0.05). Compared with P group, theWortmannin abolished the effect of increasing the expressions of p-Akt inthe postischemic rat hearts induced by propofol (P <0.05). There were nosignificant difference among I/R group, P+Wort group and Wort group.ConclusionPropofol perfusion significantly attenuated the ischemia/reperfusioninjury in the isolated rat hearts. Propofol could attenuate the endoplasmicreticulum stress pathway of apoptosis induced by ischemia/reperfusion inthe isolated rat hearts partly through PI3K/Akt signal pathway. |
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