ABSTRACT
Aim To observe the role of ERK signaling protein in morphine preconditioning reducing global ischemia-reperfusion injury in isolated rat hearts.Methods Adult male Sprague-Dawley rats were distributed into six groups (n =10 for each) using a random number table:control group (CON),ischemia-reperfusion group (I/R),ischemia preconditioning group (IPC),morphine preconditioning group at the concentration of 1 μmol · L-1 (MPC),ERK inhibitor PD98059 + MPC (MPD),and group of ERK inhibitor-PD98059 (PD).The isolated rat hearts were treated on a Langendorff perfusion apparatus system.The coronary effluent was collected at 15 min of equilibration (baseline),5 and 10 min of reperfusion for detection of the activity of LDH.Meanwhile,a water-filled balloon was inserted into the left ventricular for continuous LVDP measurement.The IS and AAR and IS/AAR ratios were observed by TTC.Western blot was used to examine the level of phosphorylated ERK in myocardium.Results As compared with the I/R group,MPC significantly decreased IS and IS/AAR ratio as well as LDH activities at 5 min and 10 min of reperfusion,but improved the LVDP at the end of reperfusion.Moreover,the phosphorylation level of ERK in myocardium was up-regulated by MPC.However,ERK inhibitor PD98059 could block the protective effects of MPC,as indicated by the increased IS and IS/AAR ratio,elevated LDH activity at the reperfusion of 5 and 10 min,and the suppressed LVDP at the end of reperfusion.Furthermore,the MPC-induced phosphorylation of ERK was also reversed by PD98059.Conclusion Morphine preconditioning may confer cardio-protection against the global ischemia-reperfusion injury in rat hearts through enhancing the phosphorylation of ERK.
ABSTRACT
Objective To observe the protective effects of hypoxic preconditioning(HPC) on the improvement of the cognitive dysfunction(learning and memory) and the damage in hippocampus induced by global cerebral ischemia/reperfusion(I/R) in CA1 and CA3 for 5 days in rats,and on the regulation of expression of erythropoietin(EPO) protein to approach the mechanism of the protection.Methods One hundred and twenty adult male Sprague-Dawley(SD) rats were divided into four groups randomly: sham group,I/R group,HPC24 group(hypoxia for 24 hours before I/R) and HPC48 group(hypoxia for 48 hours before I/R).Hang(motor function),passive avoidance and Morris water maze tests were carried out on the 5th day after I/R to measure the motor and cognition functions;hematoxylin-eosin(HE) staining was used to detected histopathological changes in hippocampus tissues;and the contents of EPO were tested by immunohistochemistry at 1 hour and 4 hours after I/R from hippocampus CA1 and CA3 regions.Results Hang,passive avoidance and Morris water maze tests showed that I/R can injure rat cognition;the improvement of cognition was marked in HPC groups, and it was shown that the effects were more significant in HPC48 group than those in the HPC24 group(P