摘要
背景:研究证实胶质细胞源性神经营养因子(GDNF)既可抗神经元凋亡,又可阻止神经细胞胞体萎缩,从而改善肠道动力,但其具体机制目前仍未完全明了。目的:研究慢传输型便秘(STC)大鼠结肠组织中GFRα1、RET、NCAM的表达以及外源性GDNF对其的影响,从而探讨GDNF保护STC大鼠结肠神经元的途径及其信号转导机制。方法:44只大鼠随机分为对照组和模型组,以大黄灌胃建立STC模型。造模成功后,对照组进一步分为正常对照组和GDNF组,模型组分为STC组和STC+GDNF组。GDNF组和STC+GDNF组大鼠尾静脉注射rhGDNF,其余两组注射0.9%NaC1溶液。1周后处死大鼠,采用免疫组化法检测结肠组织中GFRα1、RET、NCAM表达。结果:STC组GFRα1、NCAM表达较正常对照组显著减弱(P<0.05);STC组大鼠以GDNF干预后,GFRα1、NCAM表达较STC组显著增强(P<0.05);GDNF组GFRα1、NCAM表达亦较STC组、正常对照组显著增强(P<0.05)。RET仅在正常对照组结肠组织少量表达,其余各组均无表达。结论:长期使用大黄可减弱结肠组织中CFRα1、NCAM的表达,外源性GDNF可能通过GDNF-GFRα1-NCAM途径而非GDNF-GFRα1-RET途径进行信号转导,从而保护结肠神经元。
Background： Studies have demonstrated that glial cell line-derived neurotrophic factor （GDNF） can protect against neuron apoptosis and prohibit atrophy of nerve cell body, thus improving intestinal motility, however, its mechanism is still unclear. Aims： To study the expressions of GFRod, RET and NCAM in colon tissues of slow transit constipation （STC） rats and the effect of ectogenic GDNF, thereby investigating the pathway and signal transduction mechanism of protecting colonic neuron by ectogenic GDNF. Methods Forty-four rats were randomly divided into control group and model group. STC model was established by gastric infusion with rhubarb. After successfully being established model, the control group was further divided into normal control group and GDNF group, while the model group was divided into STC group and STC＋GDNF group. GDNF group and STC＋GDNF group were injected with rhGDNF via tail vein, while normal control group and STC group being injected with 0.9% NaCl solution. All the rats were sacrificed 1 week later. Immunohistochemistry was adopted to detect the expressions of GFRα1, RET and NCAM in colon tissues. Results： Expressions of GFRα1, NCAM were significantly decreased in STC group when compared with normal control group （P〈 0.05）. Expressions of GFRα1, NCAM were significantly increased in STC＋GDNF group than in STC group （P〈0.05）, and expressions of GFRα1, NCAM were also significantly increased in GDNF group than in STC group and normal control group （P〈0.05）. RET was only barely expressed in colon tissues in normal control group but was none in the other three groups. Conclusions： Long-term use of rhubarb can decrease the expressions of GFRα1, NCAM in colon tissues. Ectogenic GDNF carries out signal transduction via GDNF-GFRα1-NCAM pathway rather than GDNF-GFRα1-RET pathway, thereby protecting the colonic neuron.
出处
《胃肠病学》
2011年第11期658-661,共4页
Chinese Journal of Gastroenterology
基金
浙江省教育厅基金项目(Y200804773)资助
