| Objective N-acetylcysteine （NAC） is a precursor of intracellular glutathione（GSH）, played as antioxidant through thiol. Initially it was used as mucolytics forrespiratory diseases treatment. With the data accumulation from clinical studies, itgot applied in pulmonary fibrosis, liver fibrosis, hepatic ischemia/reperfusion, renalfailure, contrast nephropathy, myocardial ischemia/reperfusion etc. Ventricularremodeling including structural and electrical remodeling is the inevitable courseafter myocardial infarction, and is the key index determining the quality of life andthe prognosis in patients with myocardial infarction （MI）. N-acetylcysteine has apotential of inhibiting the process of ventricular remodeling, however, the underlyingmechanisms still remained to be unclear. The current study aimed to investigate themechanisms through which the improvement of left ventricular remodeling byN-acetylcysteine after myocardial infarction in rats.Methods A total of96Sprague-Dawley rats were randomly divided into twogroups: blank control （BC group, n=6）, the rest90underwent MI model. After24h.since the MI model, survived rats were randomly re-divided into NAC group （n=34）and NS group （n=32）. Rats in NAC group were intraperitoneal injected withN-acetylcysteine (0.2mg· kg-1·2d-1) for4w, while rats in NS group were given thesame volume of normal saline as control. After4w, the end-systolic left ventricularposterior wall thickness （LVPW;s）, end-diastolic left ventricular posterior wallthickness （LVPW;d）, end-systolic interventricular septal thickness （IVS;s）,end-diastolic interventricular septal thickness （IVS;d）, left ventricular ejectionfraction （LVEF）, fractional shortening （FS）, Corrected LV Mass and LV Mass Corrected LV Mass were measured by ultrasound cardiography and calculated. Thesurvival rate was calculated, the myocardial levels of GSH were measured byGSH/GSSG kit, the protein levels of kir2.1and Kv4.3were measured by Westernblot. The mRNA levels of BNP were detected by real time RT-PCR.Results NAC group LVPW;d, IVS;d、IVS;s, LVEF, FS, LV Mass and LV MassCorrected in comparison with NS group showed significant differences （2.01±0.33vs.1.64±0.37, p=0.003；1.86±0.56vs.1.30±0.26, p=0.000；2.34±0.44vs.1.51±0.31,p=0.000；36.48±0.03vs.31.18±0.07, p=0.008；18.42±0.02vs.15.50±0.04, p=0.006；1.49E3±424.63vs.1.01E3±217.80, p=0.000；1.18E3±339.70vs.8.05E2±174.24,p=0.000）. GSSG and GSH levels in NAC showed significant difference compared toNS group （42.25±0.03vs.44.63±0.03, p=0.007；21.03±0.02vs.16.71±0.03,p=0.019）. The proteins of Kir2.1and Kv4.3in in NAC showed apparent differencescompared to NS group NS （P=0.004, P=0.013）. And the mRNA levels of BNP inNAC group differed from NS group significantly （P=0.008）. However the survivalrate between NAC group and NS group showed no significant difference （P=0.084）Conclusions Although N-acetylcysteine didn’t improved the survival rate aftermyocardial infarction, the infusion of N-acetylcysteine was associated with thesignificant improvement of cardiac compliance, as showed by the of LV remodelingafter MI in rats. This cardioprotective effect by N-acetylcysteine is at least partiallyattributive to the attenuation of electrical remodeling and replenishment of GSH. |
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