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

作　　者：LU Lin ZHANG Qi PU Li-jin XU Xue-wei ZHANG Rui-yan ZHANG Jian-sheng HU Jian YANG Zheng-kun LU An-kang DING Feng-hua SHEN Jie CHEN Qiu-jin LOU Sheng FANG Dan-hong SHEN Wei-feng 

机构地区：[1]Department of Cardiology, Ruijin Hospital, Institute of Cardiovascular Disease, Medical School of Jiaotong University, Shanghai 200025, China

出　　处：《Chinese Medical Journal》2007年第6期479-484,共6页中华医学杂志（英文版）

基　　金：The study was supported by the grant from the Shanghai Natural Science Foundation(No.028610)

摘　　要：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 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）. Methods Twenty-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, asparegine 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 13 cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-β and IL-6 mFINA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction （FIT-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 had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β ceils almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Westem blot demonstrated dramaticaBackground 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 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）. Methods Twenty-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, asparegine 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 13 cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-β and IL-6 mFINA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction （FIT-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 had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β ceils almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Westem blot demonstrated dramatica

关 键 词：diabetes meUitus STREPTOZOTOCIN tumor necrosis factor-α INTERLEUKIN-1Β INTERLEUKIN-6 

分 类 号：R97[医药卫生—药品]