Effect Of Simvastatin On Tumor Necrosis Factor-alpha Of Macro-vascular In Diabetic Rats

Objective:To investigate the effect of simvastatin on tumor necrosis factor-alpha of macro-vascular in diabetic ratsMethods:Fifty-four male Wistar rats(weight from 190 to 230 gram) were randomly divided into control group(GroupA n=18),diabetes mellitus group(GroupB n=18)and Simvastatin intervention group (Group C n=18).After fasting 12 hours, GroupB and GroupC were injected intraperitoneally streptozotocin(STZ) 55mg/kg which was dissolved in citral buffer with pH=4.3,0.1mmol/l,72 hours later,the blood sugger of diabetes mellitus group above 16.7mmol/l were regard as the success of diabetes mellitus rats model; while the control ones were injected intraperitoneally the same volume of citral buffer. After one week of succession of the models,beginning to lavage to intervention group with Simvastatin 2mg.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 randomly took 6 rats, weighed body mass and measure the levels of blood glucose, Insulin and TNF-αof serum; Organizational part of the carotid artery were cut and frozen at-70℃, determined TNF-αby RT-PCR, and the other part was fixed and embeded for morphology observing. morphological changes in carotid artery the carotid artery intima-media thickness(IMT) were measured,Results:1. After 72 hours of STZ injection,compared with Group A, fasting blood glucose increased significantly in Group B and Group C(P<0.01),fasting insulin decreased significantly in Group B and Group C(P<0.01).2.Under light microscope, in Group B endothelial cells were spreaded disorderly. Smooth muscle cells were hyperplastic. The vessel wall of carotid artery is thicker and the lumens is incarcerated In Group C, compared with Group A, endothelial cells were degenerative and necrotic,and the elastic membrane was ruptured in Group B and C. There was no change in Group A. Compared with Group B, those changes significantly alleviated in Group C.3. Compared with Group A,the carotid artery intima-media thickness(IMT) of Group B was higher than that of Group A (P<0.01). compared with Group C, IMT increased significantly in Group B (P<0.01).4. Plasma TNF-αincreased significantly in Group B and Group C(P<0.01), compared with the Group C, plasma TNF-a increased significantly in Group B(P<0.01).5. RT-PCR results showed that the mRNA of TNF-αincreased significantly in Group B and Group C (P<0.01); compared with the Group C, plasma TNF-αincreased significantly in Group B (P<0.01).6. The result of linear Correlations analyse showed:the mRNA of TNF-αwere positive correlation with IMT, with the expression of mRNA of TNF-αin the carotid artery increases, IMT gradually increased.Conclusion:The increased TNF-αin the carotid artery significantly correlated with great vessel lesion of diabetic mellitus, hints that TNF-αmay participate the happen and development of great vessel lesion of diabetic mellitus and play an important role of damnification; but Simvastatin can lower the degree of TNF-αand play the role of protection.