| ObjectivePatients with diabetes shows the enhanced susceptibility to myocardialischemia/reperfusion (MI/R) injury. Epidemiological studies indicated thatconsumption of Alpha-linolenic acid (ALA) significantly reduces the risk ofcardiac events in post-acute myocardial infarction (AMI) patients. However, theeffects of ALA intake on acute myocardial injury, especially in the diabetic state,were still unlear. The present study attempted to investigate the effects of ALAintake on MI/R injury in normal and diabetic rats and its mechanisms.Methods1,The high-fat diet–fed streptozotocin (HFD-STZ) rat model wasdeveloped. Age-mathched normal and HFD-STZ rats were randomly assigned toreceive normal diet or ALA (o.g., 500μg/kg per day). For 4 weeks2,A micro-catheter was inserted into left ventricular through right carotid artery to measure the left ventricular pressure. Hemodynamic data werecontinuously monitored on a polygraph and simultaneously digitized by using acomputer interfaced with an analog-to-digital converter3,Plasma creatine kinase (CK) and lactate dehydrogenase (LDH)activities were measured spectrophotometrically (Beckman DU 640, USA) at 4hours after reperfusion. Myocardial apoptotic index was analyzed by TUNELassay. The myocardial infarct size was determined by means of a double-stainingtechnique and was analyzed by a digital imaging systems.4,Akt expression and activation (total Akt,and pAkt) were determined bywestern blotting.5 Rats were randomized to receive one of the following treatments: (1)Con; (2)Con+ALA; (3) DM; (4) DM+ALA; (5) DM+ALA+Wm. Haemodynamicswas monitored throughout the experiments.Myocardial infarct size (INF),apoptosis, inflammation, oxidative stress were determined in a blinded manner.ResultResultsCompared with the normal diet-fed control, HFD-STZ rats showed moresevere myocardial functional impirement and injury HFD-STZ. Although ALAintake for 4 wks did not change myocardial function and injury in normal rats, itsignificantly improved the instantaneous first derivation of left ventricle pressure(±LV dP/dtmax), reduced INF, plasma creatine kinase and lactate dehydrogenaseactivities, apotosis index and caspase-3 activity at the end of reperfusion in HFDSTZdiabetic rats PI3K expression and Akt phosphorylation were also increasedby ALA intake. Moreover, ALA intake significantly reduced tumor necrosisfactor-α(TNF-α) and Interleukin-6 (IL-6), and increased IL-10 concentrations indiabetic (P < 0.05) but not normal rats. Dietary ALA intake for 4 wks markedlyreduced the increase in superoxide production, gp91phox level and malonaldialdehyde formation, simultaneously enhanced the superoxide dismutaseactivity in the diabetic hearts. administration of wortmannin completelyabolished the protective effect of ALA(P<0.05).ConclusiConclusionChronic ALA intake confers cardioprotection including inhibiting apoptosisby exerting anti-inflammatory and anti-oxidative stress effects in diabetic but notnormal rats, which is possibly through PI3K-Akt-dependent mechanism. Thesedata indicate that incorporating food sources of ALA in the diet is important forthe dietary strategies for the patients with diabetes to reduce the susceptibility toMI/R injury... |
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