论文部分内容阅读
Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researcheswith respect to diabetes mellitus and cardiovascular diabetic complications.The present study aimed to establishChinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models byanalyzing inflammatory cytokine levels in aortic wall,such as tumor necrosis factor (TNF)-α,interleukin-1β(IL-1β) andinterleukin-6 (IL-6).Methods Twenty-two male Chinese Guizhou minipigs (age,4 to 6 months;weight,20 kg to 30 kg) were divided intoSTZ-induced diabetic group (n=12) and control group (n=10).STZ (125 mg/kg) was administrated to inducehyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L.Oral glucosetolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations ofalanine transaminase,asparagine transaminase,albumin,blood urea nitrogen,creatinine,lipids and white blood cellcount were measured before and six months later.Animals in both groups were euthanized after six months andpancreas was examined immunohistochemically for islet β cells.Aortic intima of diabetic minipigs and controls wasanalyzed for TNF-α level in tissue conditioned medium by Western blot.TNF-α,IL-1β and IL-6 mRNA levels in aorticintima were assayed by reverse transcription and polymerase chain reaction (RT-PCR).Results Significant 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 hadmany irregular sized islets and small clusters of islet β cells,while in pancreas of diabetic minipigs islet β cells almostdisappeared.No statistical difference was notified in serum concentrations of biochemical examinations before and sixmonths after STZ induction.Western blot demonstrated dramatically increased TNF-α level in aotic intima conditionedmedium,and significant elevation of TNF-α,IL-1β and IL-6 mRNA levels was revealed by RT-PCR.Conclusions The 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.
Background Large 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 minipig models with streptozotocin (STZ) -induced diabetes and characterize the animal models byanalyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF) -α, interleukin-1β (IL-1β) and interleukin-6 , 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 inducehyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol / L. Oral glucosetolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations ofalanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cellcount were measured before and six months later. Animals were in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet β cells. Aortic intima of diabetic minipigs and controls wasanalyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-1β and IL-6 mRNA levels in aorticintima were assayed by reverse transcription and polymerase chain reaction (RT-PCR). Results Significant 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. Normal pancreas hadmany irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β cells almost occurred. No statistical difference was notified in serum concentrations of biochemical examinations before and sixmonths after STZ induction. Western blot shows decreased increased TNF-α level in aotic intim a conditionedmedium, and significant elevation of TNF-α, IL-1β and IL-6 mRNA levels was revealed by RT-PCR. Conclusions The present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines -1β and IL-6) significantly elevated in aortic intima of diabetic minipigs.