| Objective:To investigate the effect of Simvastatin to nuclear factor-kappa B (NF-κB) tumor necrosis factor alpha (TNF-α),matrix Metalloproteinases-9 (MMP-9) in rats of type 1 diabetes cardiomyopathy.Methods:Fifty-four male Wistar rats, weight from190 to 230 gram, were randomly divided into normal control group (A n=18),diabetic rat group (B n=18) and Simvastatin treatment group (C n=18). After fasting 12 hours, Group B and Group C were injected intraperitoneally streptozotocin (STZ) 55mg/kg which was dissolved in citral buffer with pH=4.3, 0.1mmol/L, while the rats in Group A were injected citric acid buffer with the equal volume.72 hours later, the rats in Group B and Group C whose blood sugger was above 16.7mmol/L three consecutive days were regard as the success of diabetes mellitus rats model; One week later, Group C with Simvastatin 10mg.kg-1.d-1 dissolved in Sodium Chloride, then the other two groups with the same volume Sodium Chloride. At weeks of 4,8 and 12,each group take 6 rats, weighed body mass and after anesthetizing and getting blood from vena cava, then determined blood sugar and separated serum for determined Insulin of serum by RIA; take hearts, weighing, and cut off the left ventricular myocardium in the same position, partial was frozen in-70℃, for determination of NF-κB,TNF-α,MMP-9 by RT-PCR. The remaining was fixed in the 10% neutral formaldehyde for morphology observing under light microscope and determined the area of myocardial cell and for determination of NF-KB, TNF-α, MMP-9 by immunohistochemical method.Results:1. After 72 hours of STZ injection, compared with Group A, fasting blood glucose in Group B and Group C were significantly higher (P<0.01). Fasting serum insulin in Group B and Group C were significantly lower than that in Group A (P<0.01).2. Immunohistochemistry and RT-PCR results showed that 4,8,12 weeks of group B and C the mRNA of NF-KB, TNF-α, MMP-9 express increased (P＜0.01) compared with Group A. Compared with the group B, the expression of NF-KB, TNF-α, MMP-9 in Group C was significantly lower (P＜0.01 or P＜0.05).3.Under light microscope, compared with Group A, myocardial hypertrophy, rarefaction, nuclei increases, with inflammatory cells, myofibrils disorder and fragmentation, a large number of interstitial collagen fibers in extracellular matrix in Group B. With the extension of the course, large sheet of myocardial cells necrocytosis can been seen, nuclear fragmentation, disappearance, stromal cell proliferation, myofibrils fragmentation, fibrosis is more serious, while after simvastatin treatment, pathological changes in Group C is gradually improved.4. With the extension of the course, compared with Group A, At 4,8,12 weeks, the index of myocardial weight, area of myocardial cell were increased markedly in GroupB and C (P＜0.05). while the one in Group C reduced compared with Group B in the same time (P<0.05).5. The myocardial express of NF-κB,TNF-α, MMP-9 in diabetic rats is significantly corre-lated with the index of myocardial weight (NF-κB:r=0.771,P<0.01;TNF-a:r=0.684,P<0.01; MMP-9:r=0.771,P<0.01) and also significantly correlated with the area of myocardial cell (NF-κB:r=0.818,P<0.01;TNF-α:r=0.776,P<0.01; MMP-9:r=0.818,P<0.01); NF-κB with TNF-α(r=0.944,P<0.01), and with MMP-9 (r=0.952,P<0.01), TNF-αwith MMP-9 (r=0.985, P＜0.01) is also significantly correlated.Conclusions:The increased NF-κB,TNF-α,MMP-9 in myocardial tissue is significantly correlated with Diabetic Cardiomyopathy. Simvastatin may play a protective role in Diabetic Cardiomyopathy by down-regulating NF-κB,TNF-α,MMP-9.
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