ABSTRACT
Objective To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/protein-serinethreonine kinases (Akt) signaling pathway in dexmedetomidine postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in rats.Methods Seventy-two healthy male Sprague-Dawley rats,aged 4-5 months,weighing 200-240 g,were heparinized and anesthetized with intraperitoneal pentobarbital sodium 40 mg/kg.Their hearts were rapidly excised and perfused in a Langendorff apparatus with oxygenated (95％ O2-5％ CO2) K-H solution at 0-4℃.The isolated hearts were randomly divided into 6 groups (n =12 each):control group (group C),group I/R,dexmedetomidine postconditioning group (gruop D),solvent group (group DMSO),PI3K inhibitor LY294002 group (group L) and LY294002 + dexmedetomidine postconditioning group (group L + D).After a 20 min stabilization period,the hearts were continuously perfused with K-H solution for 120 min in group C and were subjected to 30 min of global no-flow ischemia followed by 90 min of repeffusion in the other groups.Dexmedetomidine 100 nmo/L was added during the initial 30 min of reperfusion in D and L + D groups.LY294002 15 μmol/L was added in L group.0.02％ DMSO containing 15 μmol/L LY294002 was added in L + D group.0.02％ DMSO was added in DMSO group.HR,left ventricular end-diastolic pressure,left ventricular developed pressure and ± dp/dtmax were recorded at the end of 20 min stabilization and 15,30 and 90 min of reperfusion.The expression of phosphorylated Akt (p-Akt) and Akt was measured at 30 min of reperfusion.Myoeardial infarct size was determined using TTC staining at 90 min of reperfusion.Results Compared with group C,HR,left ventricular developed pressure and ± dp/dtmax were significantly decreased,and left ventricular enddiastolic pressure and myocardial infarct size were increased in the other 5 groups,and the expression of p-Akt was significantly up-regulated in group D (P ＜ 0.05).Compared with group I/R,HR was significantly decreased at 15 and 30 min of reperfusion,the expression of p-Akt was up-regulated,and myocardial infarct size was decreased in group D (P ＜ 0.05).Compared with group D,the expression of p-Akt was down-regulated,and myocardial infarct size and HR was increased in L + D group (P ＜ 0.05).Conclusion Dexmedetomidine postconditioning attenuates myocardial I/R injury throuth activating PI3K/Akt signaling pathway in rats.
ABSTRACT
Objective: To study the interaction between the calcium channel antagonist nimodipine and growth factors (vascular endothelial growth factor [VEGF] and platelet-derived growth factor[PDGF]) during the formation of new retinal vessels. Methods: The hyperoxia model was induced by proliferative retinopathy (OIR) in newborn Sprague-Dawley (SD) rats. SD rats (2 d after birth) were randomized into 5 groups: normal control group, pure OIR group and group 3, 4 and 5, where the animals received retrobulbar injection of nimodipine 10 ?l, 5 ?l and 2 ?l once every 2 d for 3 times, respectively. Both eyeballs of newborn rats were made into common pathological sections and detected by immunohistochemistry method to count the nuclei of proliferative retinal vessel cells and to investigate the expression of VEGF and PDGF in retina. Results: The nuclei of proliferative retinal vessel cells and the expressions of VEGF and PDGF in pure OIR group increased significantly compared to those of normal control group(P