糖基化终末产物对大鼠海马结缔组织生长因子与炎症因子表达的影响

The effect of advanced glycation endproducts on CTGF and inflammatory cytokines secretion from rat hippocampus

目的探讨糖基化终末产物(AGEs)对大鼠海马区结缔组织生长因子(CTGF)与炎症因子白细胞介素1β(IL-1β)、肿瘤坏死因子(TNF-α)表达的影响及其可能的机制。方法 50只Wistar大鼠随机分为5组(每组10只),各组用微量注射泵海马内注射法制造动物损伤模型。3周后:通过免疫组织化学检测各组大鼠海马转化生长因子β1(TGF-β1)、CTGF表达;通过Westernblot检测大鼠海马TGF-β1、CTGF以及炎症因子IL-1β和TNF-α表达并进行蛋白半定量分析。结果在AGE-BSA组大鼠的大脑海马区神经元内TGF-β1、CTGF着色呈棕黄色,颜色灰度明显高于正常对照组;AGE-BSA组TGF-β1、CTGF、IL-1β和TNF-α蛋白表达明显高于正常对照组(P<0.01);与AGE-BSA组比较,RAGE中和抗体组TGF-β1、CTGF、IL-1β和TNF-α蛋白表达明显减少(P<0.05)。结论糖基化终末产物通过与其受体(RAGE)结合促进TGF-β1的表达上调,进而导致海马区神经元内CTGF的高表达,而且可以造成炎症因子IL-1β和TNF-α表达增多。

Objective To explore the effect of advanced glycation end products（AGEs）on the expression of connective tissue growth factor（CTGF） in rat brain and the possible mechanism. Methods 50 Wistar rats were randomly divided into 5 groups（n = 10）and the hippocampus in each group was injected and produced to animal injury models by using micro-injection pump. 3 weeks later, immunohistochemistry was employed to examine the protein expression of TGF-β1 and CTGF; Western blot was performed to detect the expression of TGF-β1 ,CTGF, IL- β1 and TNF-α protein expression in rat hippocampus. Results In the hippocampus of AGE-BSA group, TGF-β1 and CTGF were lightered brownish-yellow. The grayscales was higher than NC group. The TGF-β1, CTGF protein expression in AGE-BSA group were higher than that in NC group respectively（P 〈 0. 01 ）. Compared with AGE-BSA group,TGF-β1 ,CTGF,IL-1β and TNF-α protein expression in RAGE-Ab group significantly reduced（ P 〈 0. 05 ）. Conclusions AGEs may promote the expression of TGF-1β by binding with its receptor（ RAGE）, which leads to increase the CTGF expression in hippocampal neurons of rats, also promote the expression of IL-1β and TNF-α.