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糖尿病对大鼠结肠胶质纤维酸性蛋白和神经营养因子表达的影响。

Effects of diabetes on expression of glial fibrillary acidic protein and neurotrophins in rat colon.

机构信息

Department of Pediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.

出版信息

Auton Neurosci. 2010 Apr 19;154(1-2):79-83. doi: 10.1016/j.autneu.2009.12.003. Epub 2009 Dec 29.

Abstract

Diabetes can result in loss of enteric neurons and subsequent gastrointestinal complications, but the influence of diabetes on the expression of glial fibrillary acidic protein (GFAP) and neurotrophins in gut remains unknown. The aim of this study was to determine the changes of GFAP and neurotrophins in the colon of diabetic rats. The distribution of the glial marker-GFAP was explored by immunofluorescence histochemistry and western blot in colons of streptozotocin (STZ)-diabetic and age-matched control rats. And the expression of glia cell-derived neurotrophic factor (GDNF), neurotrophin 3 (NT-3) and nerve growth factor (NGF) was analyzed by real-time PCR and western blot. Studies were carried out at 4 and 12weeks of diabetes duration. Immunostaining and western blot showed diabetes induced a decrease in the intensity of staining of GFAP positive enteric glial cells (EGCs) and GFAP protein levels at 4weeks and attenuated GFAP expression was more evident at 12weeks. Moreover, mRNA and protein analysis indicated that the levels of GDNF, NT-3 and NGF were down-regulated in diabetic rats. These findings suggest that the induction of diabetes is associated with a reduction in GFAP and neurotrophins expression in the colon, which may affect the role of EGCs and neurotrophins in the enteric plexus. This in turn may partly contribute to the physiopathologic changes associated with diabetic state in the gastrointestinal tract.

摘要

糖尿病可导致肠神经元丧失和随后的胃肠道并发症,但糖尿病对肠道胶质纤维酸性蛋白(GFAP)和神经营养因子表达的影响尚不清楚。本研究旨在确定糖尿病大鼠结肠中 GFAP 和神经营养因子的变化。通过免疫荧光组织化学和western blot 检测链脲佐菌素(STZ)-糖尿病大鼠和年龄匹配的对照组大鼠结肠中神经胶质标志物-GFAP 的分布。通过实时 PCR 和 western blot 分析胶质细胞源性神经营养因子(GDNF)、神经生长因子 3(NT-3)和神经生长因子(NGF)的表达。研究在糖尿病持续 4 周和 12 周时进行。免疫染色和 western blot 显示,糖尿病在 4 周时诱导 GFAP 阳性肠神经胶质细胞(EGCs)的染色强度和 GFAP 蛋白水平降低,而在 12 周时 GFAP 表达减弱更为明显。此外,mRNA 和蛋白分析表明,糖尿病大鼠中 GDNF、NT-3 和 NGF 的水平下调。这些发现表明,糖尿病的诱导与结肠中 GFAP 和神经营养因子表达的减少有关,这可能影响 EGCs 和神经营养因子在肠丛中的作用。这反过来可能部分导致与胃肠道中糖尿病状态相关的生理病理变化。

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