| Objective: To investigate the effect of Losartan and simvastatin on CTGF and TGF-β1expression in Rats of type 1 Diabetic CardiomyoPathy disease, and the protection to DiabeticCardiomyoPathy, provide experimental basis for clinical treatmentMethods: Ninety male Wistar rats,weight from 200 to 250 gram,were randomly dividedinto normal control group (NC, n=18),diabetic rat group (DM, n=18),Losartan treatment group(DM-L, n=18),simvastatin treatment group (DM-S, n=18) and both Losartan and simvastatintreatment group (DM-SL, n=18). After fasting 12 hours,Group DM,Group DM-L,GroupDM-S and Group DM-SL were injected intraperitoneally streptozotocin (stz) 55mg/kg whichwas dissolved in citral buffer with PH=4.3,0.1mmol/L,while the rats in Group NC were injectedcitric acid bufferr with the equal volume. 72 hours later,the rats in Group DM,Group DM-L,Group DM-S and Group DM-SL whose blood sugger was above 16.7mmol/L three consecutivedays were regard as the success of diabetes millitus rats model. One week later, Group DM-Lwere daily gavaged with the suspension of Losartan (50mg.kg-1.d-1) and physiological saline,Group DM-S were daily gavaged with the suspension of Simvastatin (10mg.kg-1.d-1) andphysiological saline, Group DM-SL were daily gavaged with the suspension of Losartan(50mg.kg-1.d-1),simvastatin (10mg.kg-1.d-1) and physiological saline. At weeks of 4,8 and 12,each group take 6 rats, tested the blood sugar,insulin,heart weight index and area of myocardialcell, examined the protein expression of CTGF and TGF-β1 in the heart of rats byImmunohistochemistry, determined the mRNA expression of CTGF and TGF-β1 in the heart ofrats by real time RT-PCR.Results:1. Pairwise comparison of each group over the same period: compared with Group NC, thefasting glucose of rats of all Group of diabetic models was significantly higher, and thedifferences were statistically significant(P﹤0.05), but the differences in all Groups of diabeticmodel were not statistically significant(P＞0.05)；compared with Group NC, the fasting seruminsulin of rats in all Group of diabetic model was significantly lower, and the differences werestatistically significant(P﹤0.05),but the differences in all Group of diabetic model were notstatistically significant(P＞0.05).2. Under Optical microscope,we observed the HE dyeing slices,we saw myocardial collagenfibers of Group NC were slim,equally distributed, and orderly,nuclei is ronund or oval, in thecenter of the myocardial cells. To Group DM, at 4 weeks, we found myocardial cells were hypertrophy, nuclei increases, myocardial fiber were disordered arrangement; at 8 weeks,pathological changes mentioned above continued development, Regional myocardial fiberfracture fragments can be seen, with inflammatory cell infiltrated, a large number of collagenfibers appeared in Myocardial interstitial; at 12 weeks, cardiomyopathy developed further more,we found myocardial cell swelling, necrosis, ill-defined, nuclear sizes, myocardial interstitialfibrosis, myocardial fiber arrangement is more obviously disordered. The pathological changesof all Groups of drug intervented were reduced in varying degrees with the time going,especially in Group DM-SL reduced most significantly.3. Pairwise comparison of each group over the same period: the heart weight index and thearea of myocardial cells of all Groups of diabetic model were increased compared with theGroup NC(P﹤0.05), and all Groups of drug intervented were decreased compared with theGroup DM(P﹤0.05), Group DM-SL decreased the most, but the difference between the GroupDM-L and Group DM-S was not statistically significant(P＞0.05).4. Pairwise comparison of each group over the same period: the protein expression of CTGFand TGF-β1 in the heart of rats of all Groups of diabetic model were increased compared withthe Group NC(P﹤0.05), and all Groups of drug intervented were decreased compared with theGroup DM(P﹤0.05), Group DM-SL decreased the most, but the difference between the GroupDM-L and Group DM-S was not statistically significant(P＞0.05).5. Pairwise comparison of each group at 12 weeks: the mRNA expression of CTGF andTGF-β1 in the heart of rats of all Groups of diabetic model were increased compared with theGroup NC(P﹤0.05), and all Groups of drug intervented were decreased compared with theGroup DM(P﹤0.05), Group DM-SL decreased the most, but the difference between the GroupDM-L and Group DM-S was not statistically significant(P＞0.05).6. Pearson correlation analysis showed that the protein expressions between TGF-β1 andCTGF is significantly positive correlation(r0=0.791,P<0.01); TGF-β1 protein and CTGFprotein is positively correlate with heart weight index and cardiac cell area (correlationCoefficients were respectively: r1 = 0.782, r2 = 0.691, r3 = 0.901, r4 = 0.869, P <0.01).Conclusion: the increased expression of CTGF and TGF-β1 in myocardial tissue is closelyrelated to the occurrence of the diabetic cardiomyopathy. Losartan and simvastatin candown-regulated the expression of CTGF and TGF-β1 in myocardial tissue, play acardioprotective effect. Combination of the two drugs may have a synergistic effect. |
PDF Full Text Request