The Protective Effects Of N-acetylcy-steine On Cardiomyopathy Fibrosis In Diabetic Rat

ObjectiveTo observe the oxidative stress response, transforming growth factor-β1,SMAD3and SMAD7levels on N-acetylcysteine in diabetic rats. The protectiveeffects and mechanism of N-acetylcysteine on cardiac muscle were investigatedin diabetic rat, in order to provide the basic theory foundation for clinicalintervention on the occurrence and development of diabetic cardiomyopathy.MethodsThe fifty male SD rats were helthy, ten rats were randomly selected to thenormal control group(CON), the fifty rats were establested diabetesmellitus ratmodel by tail vein injection of streptozotocin of30mg/kg, The establested DM ratmodel were randomly divided into diabetic model group (DM), the low, middle,high doses of N-acetylcysteine therapy group. N-acetylcysteine of50,100,200mg/kg was respectively given to the low, middle, high doses of drug therapygroups by gavage for12weeks. The blood glucose, hemodynamic, heart qualityindex (HMI) and left ventricular mass index (LVMI) of Rats were calculated, theactivities of SOD and GSH-PX were measured with serum and heart tissue;Morphological changes was observed and myocardial collagen volume fraction(CVF) was measured by Masson staining; The mRNA and protein expressionlevels of TGF-β1, SMAD3and SMAD7were determined by RT-PCR andimmunohistochemistry. Results1.Compared with the CON, the blood glucose of DM were significantlyup-regulated (P<0.01), and fluctuating at a high level,±dp/dtmaxweresignificantly reduced (P<0.01); HMI and LVMI were higher (P<0.01); Comparedwith the DM, the changes of NAC treatment groups in blood glucose was nosignificant difference,±dp/dtmaxwere significantly up-regulated (P<0.01), HMIand LVMI were reduced (P<0.01), and dose-dependent(P<0.01).2.The cardiac muscle fibers of CON were Integrity, morphological wasregulared; Compared with the CON, the cardiac muscle fibers of DM werederangement and collagen fibers were increased; The levels of CVF weresignificantly up-regulated (P<0.01); Compared with the DM, the pathologicalchanges of NAC treatment groups were improved significantly, CVF werereduced(P<0.01).3.Compared with the CON, the activities of SOD and GSH-PX DM of DMwere significantly reduced (P<0.01); Compared with the DM, the activities ofSOD and GSH-PX of NAC treatment groups were significantly up-regulated,high dose group had been improved obviously (P<0.01).4.Compared with the CON, the mRNA and protein expression levels ofTGF-β1and SMAD3of DM were significantly up-regulated reduced (P<0.01),The mRNA and protein expression levels of SMAD7was reduced significantly(P<0.01); Compared with the DM, the mRNA and protein expression levels ofTGF-β1and SMAD3of NAC treatment groups were significantly reduced(P<0.01), The mRNA and protein expression level of SMAD7were up-regulatedsignificantly,high dose group had been improved obviously(P<0.01).ConclusionThe Oxidative stress involved in the process of the diabetic cardiomyopathy,N-acetylcysteine can retard the progression of cardiac remodeling diabetic. Themechanism maybe related to inhibit the Oxidative stress, reduce the mRNA and protein expression levels of TGF-β1, SMAD3and up-regulate the level ofSMAD7.