| Objective: To investigate the effect of Simvastatin to tumor necrosis factor alpha(TNF-α) in rats of type 1 diabetes kidney disease.Methods: Fifty-four male Wistar rats(weight from 190 to 230 gram) were randomly divided into control group(n=18),diabetes mellitus group(n=18)and Simvastatin intervention group (n=18).After fasting 12 hours, diabetes mellitus group and Simvastatin intervention group 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 took 6 rats, weighed body mass and collected 24 hours urine by metabolism cage,determined blood sugar,urine albumin excretion rate;after anesthetizing and getting blood from vena cava,separated serum and determined creatinine, urea nitrogen, Insulin and TNF-αof serum;cut kidneys,the left one was frozen in -70℃,determined TNF-αby RT-PCR,the right one was fixed and embeded for morphology observing.Results:1,After 72 hours of STZ injection,compared with control group, fasting blood glucose increased significantly in diabetes mellitus group and Simvastatin intervention group (P<0.01),fasting insulin decreased significantly in diabetes mellitus group and Simvastatin intervention group(P<0.01).2,With the course of disease,there was more albuminuria in excretion,larger glomerular volume in diabetes mellitus group and Simvastatin intervention group(P<0.01), diabetes mellitus group changed larger than Simvastatin intervention group(P<0.01).3,Plasma TNF-αincreased significantly in diabetes mellitus group and Simvastatin intervention group(P<0.01), compared with the intervention group,plasma TNF-αincreased significantly in diabetes mellitus group (P<0.01).4,RT-PCR results showed that the mRNA of TNF-αincreased significantly in diabetes mellitus and intervention groups (P<0.01); compared with the intervention group,plasma TNF-αincreased significantly in diabetes mellitus group (P<0.01).Conclusion: The increased TNF-αin kidney significantly correlated with diabetes kidney disease(r=0.919,P<0.001) hints that TNF-αmay participate the happen and development of diabetes kidney disease and play an important role of damnification;but Simvastatin can lower the degree of TNF-αand play the role of protection.
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