Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, China.
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
Sci Rep. 2018 Jun 21;8(1):9437. doi: 10.1038/s41598-018-27787-2.
Present study aims to investigate the role of AGEs, TGF-β1, BDNF and their receptors on diabetes-induced colon remodeling. Diabetes was induced by a single tail vein injection 40 mg/kg of STZ. The parameters of morphometric and biomechanical properties of colonic segments were obtained from diabetic and normal rats. The expressions of AGE, RAGE, TGF- β1, TGF- β1 receptor, BDNF and TrkB were immunohistochemically detected in different layers of the colon. The expressions of AGE, RAGE, TGF-β1 and TGF- β1 receptor were increased whereas BDNF and TrkB were decreased in the diabetic colon (P < 0.05, P < 0.01). AGE, RAGE and TGF-β1 receptor expressions were positively correlated whereas the BDNF expression was negatively correlated with most of the morphometry and biomechanical parameters (P < 0.05, P < 0.01, P < 0.001). AGE, TGF- β1 and BDNF in different layers correlated with their receptors RAGE, TGF- β1 receptor and TrkB respectively. STZ-induced diabetes up-regulated the expression of AGE, RAGE, TGF- β1 and TGF- β1 receptors and down-regulated BDNF and TrkB in different layers of diabetic colon mainly due to hyperglycemia. Such changes maybe important for diabetes-induced colon remodeling, however it is needed to further perform mechanistic experiments in order to study causality or approaches that explain the relevance of the molecular pathways.
本研究旨在探讨 AGEs、TGF-β1、BDNF 及其受体在糖尿病诱导的结肠重塑中的作用。糖尿病通过单次尾静脉注射 40mg/kg STZ 诱导。从糖尿病和正常大鼠中获得结肠节段形态和生物力学特性的参数。采用免疫组织化学方法检测不同层次结肠中 AGE、RAGE、TGF-β1、TGF-β1 受体、BDNF 和 TrkB 的表达。糖尿病结肠中 AGE、RAGE、TGF-β1 和 TGF-β1 受体的表达增加,而 BDNF 和 TrkB 的表达减少(P<0.05,P<0.01)。AGE、RAGE 和 TGF-β1 受体的表达与大多数形态和生物力学参数呈正相关,而 BDNF 的表达与大多数形态和生物力学参数呈负相关(P<0.05,P<0.01,P<0.001)。不同层次的 AGE、TGF-β1 和 BDNF 分别与 RAGE、TGF-β1 受体和 TrkB 及其受体相关。STZ 诱导的糖尿病主要由于高血糖而上调糖尿病结肠不同层次的 AGE、RAGE、TGF-β1 和 TGF-β1 受体的表达,并下调 BDNF 和 TrkB 的表达。这些变化可能对糖尿病诱导的结肠重塑很重要,但需要进一步进行机制实验,以研究因果关系或解释分子途径相关性的方法。