脱细胞膀胱粘膜下基质在尿道下裂修复中的临床应用及尿道下裂病因学研究

【作者】 吴意光；

【导师】 李森恺；

【作者基本信息】 中国协和医科大学 ， 整形外科， 2005， 博士

【摘要】 尿道下裂是男性泌尿生殖系统常见的先天性畸形，发病率约为千分之一至千分之三，患者不能站立排尿，严重影响了患者的生活质量，手术重建尿道是最主要的治疗方法，目前手术方法众多，但是由于自体组织来源有限，效果并不理想，术后并发症较多，因此我们在动物实验的基础上于国内首次尝试应用同种异体脱细胞膀胱黏膜下基质来修复阴茎型尿道下裂以改善尿道下裂的临床治疗；同时鉴于大部分尿道下裂患者的病因不明，我们拟建立稳定可靠的尿道下裂动物模型以指导对尿道下裂病因学方面的研究。 人类尿道下裂的发病率近年来增长迅速，尿道下裂与环境污染的相关性不容忽视，目前随着工业化进程加速，全球化学合成物种类越来越多，环境污染日趋严重，各种生物变异现象层出不穷。许多化学合成物并未进行严格的致畸、致癌、致突变实验，生殖健康方面的影响更是无法预料。莠去津(除草剂)现在已被欧盟全面禁止，美国正在开展对它的应用评估，但是我国仍在大量供应和使用，其对人类的影响究竟如何，目前尚无定论，我们试图探讨莠去津是否具有类雌激素样作用、胚胎致畸作用及其对尿道下裂的发病率的影响，国内未见类似的报道。 一、脱细胞膀胱粘膜下基质尿道下裂修复的临床应用研究 我们采用反复冻融-酶法获得了脱细胞膀胱粘膜下基质，在口腔粘膜接种实验、大鼠腹部肌肉移植实验、新西兰白兔中段尿道缺损(1cm×0.5cm)修复等等实验的基础上于2004年将同种异体脱细胞膀胱黏膜下基质试用于3例阴茎型尿道下裂患者的治疗。 结果： 1)HE染色显示脱细胞膀胱粘膜下基质采用反复冻融-酶法脱细胞完全，Masson染色染色组织学观察显示脱细胞基质的主要成分为胶原，采用冷冻干燥技术处理脱细胞膀胱粘膜下基质得到冻干材料，组织学和扫描电镜观察证实其具有三维立体网络状结构。 2)2例一期手术患者尿线粗、直，无尿瘘，无散射：术后1年随访，阴茎无下弯，无尿痛、尿瘘，尿线粗，尿流测定仪及尿道镜检查未见异常。另1例二期手术患者，电话随访远端尿道未见狭窄及闭锁。 结论如下： 1．反复冻融-酶法和冷冻干燥技术处理膀胱粘膜下层可以获得冻干脱细胞膀胱粘膜下基质，呈三维立体网络状结构，组织相容性好，能够在新生组织形成过程中逐渐降解吸收，符合组织工程支架材料的要求。 2．应用同种异体脱细胞膀胱粘膜下基质重建阴茎远端型尿道下裂的尿道，术后1年近期效果满意，表明同种异体脱细胞膀胱粘膜下基质是一种有前途的较为理想的尿道组织修复替代材料，远期效果还有待继续进行严密仔更多还原

【Abstract】 Hypospadias is one of the most common congenital deformity in males with a reported incidence of 3/1000 live male births. There is an increasing tendence in the incidence rate of hypospadias in many countries. The cause of most cases of hypospadias is unclear. The relating studies showed that the pathogenies of hypospadias were related to genetic factors and environmental factors.Recent epidemiologic studies suggest that parents working in areas of high pesticide application are at increased risk for adverse reproductive outcomes such as infertility ,poor fertilization, fetal death and congenital abnomalies .Residential pesticide exposures and their effects on reproductive health or sexual mal-differentiation are less-well understood.In the recent years, a great deal of attentive has focused on the global presence of endocrine-disrupting contaminants in the environment .Atrazine(2-chloro-4-ethylamino-6-isopropylamine-1,3,5-triazine) is the most commonly used herbicide in the US and our country. The US Department of Agriculture reports that more than 30,000 tons are used annually in the US alone ,and currently Atrazine is used in more than 80 countries .It is applied to control weeds in corn and sorghum fields ,both prior to and following emergence ,As a result of this widespread use , Atrazine is the most frequently detected pesticide in ground and surface water ,Therefore ,humans and wildlife are at risk for exposure to Atrazine.Atrazine has also been reported to affect endocrine function in the male. Some scholars reported it can reduce production of testosterone in juvenile rats .Atrazine, a triazine herbicide marketed by Ciba-Geigy throughout the United Stated and our country, but was forbidded in Europen Union. It is unknown whether Atrazine can induce hypospadias in animal experiment. So we更多还原