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 est...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 dramatica展开更多
目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interle...目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18)在急性脑梗死患者血浆中的表达及意义。方法:纳入急性脑梗死患者85例为脑梗死组,根据神经功能缺损严重程度、脑梗死面积及发病后第90天的改良Rankin量表(Modified Rankin Scale,mRS)评分分为轻、中及重度组,小、中及大面积组,预后良好组及预后不良组。纳入同期健康体检者85例为对照组。采用酶联免疫吸附(enzyme-linked immunosorbnent assay,ELISA)法检测AIM2、IL-1β和IL-18在这两组人群血浆中的表达水平。结果:脑梗死组血浆AIM2、IL-1β和IL-18水平均明显高于对照组,差异均具有统计学意义(均P<0.001)。脑梗死组亚组比较示:患者血浆AIM2、IL-1β和IL-18水平在重度神经功能缺损严重程度组>中度组>轻度组,在大面积脑梗死组>中面积组>小面积组,在预后不良组>预后良好组,差异均具有统计学意义(均P<0.05);血浆AIM2水平与美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死面积及mRS评分呈正相关(分别r=0.791、r=0.710、r=0.763,均P<0.001),IL-1β水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.716、r=0.690、r=0.688,均P<0.001),IL-18水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.714、r=0.638、r=0.653,均P<0.001);血浆AIM2与IL-1β、IL-18水平呈正相关(分别r=0.828、r=0.751,均P<0.001)。结论:AIM2、IL-1β和IL-18在急性脑梗死患者血浆中表达上调,而且与急性脑梗死患者的神经功能缺损严重程度、脑梗死面积及预后密切相关,提示AIM2、IL-1β和IL-18可能在急性脑梗死的发生、发展中起重要作用。展开更多
基金supported by grants from the National Natural Science Foundation of China (No. 81571169)the Military Medical Research Project of China (No. AHJ16J001)
基金The study was supported by the grant from the Shanghai Natural Science Foundation(No.028610)
文摘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 dramatica
文摘目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18)在急性脑梗死患者血浆中的表达及意义。方法:纳入急性脑梗死患者85例为脑梗死组,根据神经功能缺损严重程度、脑梗死面积及发病后第90天的改良Rankin量表(Modified Rankin Scale,mRS)评分分为轻、中及重度组,小、中及大面积组,预后良好组及预后不良组。纳入同期健康体检者85例为对照组。采用酶联免疫吸附(enzyme-linked immunosorbnent assay,ELISA)法检测AIM2、IL-1β和IL-18在这两组人群血浆中的表达水平。结果:脑梗死组血浆AIM2、IL-1β和IL-18水平均明显高于对照组,差异均具有统计学意义(均P<0.001)。脑梗死组亚组比较示:患者血浆AIM2、IL-1β和IL-18水平在重度神经功能缺损严重程度组>中度组>轻度组,在大面积脑梗死组>中面积组>小面积组,在预后不良组>预后良好组,差异均具有统计学意义(均P<0.05);血浆AIM2水平与美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死面积及mRS评分呈正相关(分别r=0.791、r=0.710、r=0.763,均P<0.001),IL-1β水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.716、r=0.690、r=0.688,均P<0.001),IL-18水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.714、r=0.638、r=0.653,均P<0.001);血浆AIM2与IL-1β、IL-18水平呈正相关(分别r=0.828、r=0.751,均P<0.001)。结论:AIM2、IL-1β和IL-18在急性脑梗死患者血浆中表达上调,而且与急性脑梗死患者的神经功能缺损严重程度、脑梗死面积及预后密切相关,提示AIM2、IL-1β和IL-18可能在急性脑梗死的发生、发展中起重要作用。
