Elevation of tumor necrosis factor-α, interleukin-1β and interleukin-6 levels in aortic intima of Chinese Guizhou minipigs with streptozotocin-induced diabetes

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BackgroundLarge animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6).MethodsTwenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n=12) and control group (n=10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet β cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-1β and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR).ResultsSignificant elevation in serum glucose levels was observed one month and six months after STZ induction (P<0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-α level in aotic intima conditioned medium, and significant elevation of TNF-α, IL-1β and IL-6 mRNA levels was revealed by RT-PCR.ConclusionsThe present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-α, IL-1β and IL-6) significantly elevated in aortic intima of diabetic minipigs.Chin Med J 2007;120(6):479–484

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