一氧化氮合酶在糖尿病结肠功能紊乱大鼠结肠壁的表达及意义AP-1对酒精致纹状体突触可塑性变化影响的研究

【作者】 周蓉；

【导师】 戈应滨； 袁孝如；

【作者基本信息】 南京医科大学 ， 生理学， 2005， 硕士

【摘要】 糖尿病结肠功能障碍是糖尿病(DM)极为常见并发症,该病的突出的临床症状为腹胀和便秘。近年来糖尿病结肠功能紊乱的研究热点主要集中于神经、胃肠激素以及肠血管病变上,但是糖尿病结肠肠功能紊乱的发病机制目前仍未明确。 一氧化氮(NO)是新近发现的一种重要的生物信息递质,广泛参与生理功能的调节。NO在其限速酶一氧化氮合酶(NOS)的作用下生成。NOS分为三型:神经型NOS(nNOS)、内皮细胞型NOS(eNOS)、诱生型NOS(iNOS)。众多研究表明,胃肠动力障碍疾病与一氧化氮(NO)及一氧化氮合成酶(NOS)的异常有关。因此我们通过糖尿病大鼠模型,研究结肠内各型NOS表达情况、组织学分布的差异及其在该疾病发生展中的作用,探讨糖尿病结肠功能障碍发生、发展可能机制。 实验用采用单剂量腹腔注射100mg/kg链脲佐菌素(STZ)法建立糖尿病大鼠模型。造模4w后取糖尿病大鼠近端结肠、远端结肠组织,用免疫组化法观察nNOS、eNOS、iNOS阳性细胞在结肠不同部位的分布情况,用RT-PCR法观察上述NOS的三种亚型mRNA的表达情况。结果如下(1) 免疫组织化学方法显示神经型一氧化氮合酶(nNOS)在病例组和正常组大鼠结肠壁均有表达;eNOS在糖尿病组和正常组大鼠结肠中大多数无明显表达,仅有少数可见弱阳性表达。诱导型NOS(iNOS)在两组中均无表达。(2) RT-PCR显示nNOS在糖尿病大鼠近端结肠、远端结肠表达增多;eNOS糖尿病大鼠近端结肠、远端结肠表更多还原

【Abstract】 Colonic dysfunction is a frequent complication of diabetes mellitus, and constipation is the most common clinical situation. Even though autonomic neuropathy 、 gastrointestinal hormone and vasodilation dysfunction are regarded as the important mechanisms of Colonic dysfunction, it requires further clarification..It has been demonstrated that Nitric oxide (NO) is a simple and unique molecule that can serve many diverse functions, including those as an ntracellular second messenger and intercellular messenger.NO is produced from 1-arginine by the activation of NO synthase (NOS). There are three isoforms of NOS that are products of distinct genes. They are Neuronal NOS (nNOS)、 endothelial NOS (eNOS) and inducible NOS (iNOS).NO and its synthesizing enzyme NOS seem to be involved in colonic dysfunctiono In this study we investigated the expression of three subtypes of NOS in the colon of diabetic rats, and to explore the relation between colonic dysfunction and NOS expression.Sprague-Dawley (SD) rats were used in this experiment. Diabetic rats were induced by streptozotocin (100mg/kg, i.v.). Three isozymes of NOS (nNOS, iNOS and eNOS) expression in proximal and distal colon were measured in 4 weeks after diabetes induction through the methods of immunocytochemistry and semi-quantitative reverse更多还原