结缔组织生长因子在神经源性膀胱纤维化过程中的影响因素研究  

Role of connective tissue growth factor in bladder fibrosis of patients with neurogenic bladder

作　　者：刘倩[1] 王军锋[1] 马楠[1] 刘三咪[1] 徐加龙[1] 孙小刚[1] 陈维秀[1] 李金良[1] 王若义[1] Liu Qian;Wang Junfeng;Ma Nan;Liu Sanmi;Xu Jialong;Sun Xiaogang;Chen Weixiu;Li Jinliang;Wang Ruoyi(Department of Pediatric Surgery,Second Hospital of Shandong University,J inan 250033,Chin)

机构地区：[1]山东大学第二医院小儿外科 ,济南250033

出　　处：《中华小儿外科杂志》2018年第7期539-545,共7页Chinese Journal of Pediatric Surgery

基　　金：山东省医药卫生科技发展计划项目 （2016WS0337）

摘　　要：目的观察大鼠膀胱出口梗阻模型及膀胱去神经模型膀胱结缔组织生长因子（CTGF）的变化规律，明确引起其变化的影响因素，为神经源性膀胱纤维化的早期预防和治疗提供理论依据。方法取70只雌性Wistar大鼠，完全随机分为3组，A组（膀胱出口梗阻模型）30只；B组（膀胱去神经模型）20只；C组（对照组）20只。分别于手术后第10天、30天，在每组中完全随机选出10只大鼠行尿流动力学检查、摘取膀胱组织，行切片HE染色和结缔组织生长因子（connective tissue growth factor，CTGF）单克隆抗体免疫组化染色。结果尿流动力学变化：A组术后10 d与术后30 d膀胱灌注量和膀胱逼尿肌压均比C组明显增加（P〈0.05），膀胱顺应性在术后第10天与C组比较，差异无统计学意义（P〉0.05），术后第30天较C组明显降低（P〈0.05）。B组膀胱去神经后膀胱容量和顺应性比C组增大，膀胱逼尿肌压较对照组明显减小（P〈0.05）。膀胱组织HE染色结果：A组膀胱肌层增厚，平滑肌细胞肥大，细胞核深染，有炎性细胞浸润；B组膀胱壁无明显增厚，平滑肌细胞无明显增生、肥大，平滑肌细胞排列紊乱，炎症细胞浸润表现明显。膀胱组织CTGF免疫组化染色：A组平滑肌细胞及黏膜移行上皮细胞可见明显黄染，平滑肌细胞内可见粗大的棕色颗粒沉积，CTGF的表达在术后10 d为81.86±4.40，术后30 d为127.32±9.37，分别较对照组的33.87±5.31显著升高（P〈0.05）；B组平滑肌细胞及移行上皮细胞可见黄染，可见有棕色颗粒沉积，CTGF的表达在术后10 d为51.46±5.89，术后30 d为77.81±8.15，分别较对照组的33.87±5.31显著升高（P〈0.05）。结论膀胱内高压可以使膀胱壁平滑肌细胞明显增生，膀胱顺应性降低。膀胱去神经短期内可增加膀胱顺应性。膀胱内高压和膀胱去神经两种因素均可促使膀胱组织内结缔组织生长因�ObjectiveTo explore the changes of bladder connective tissue growth factor （CTGF） in a rat model of bladder outlet obstruction and bladder denervation and identify the major influencing factors for the distribution of CTGF in bladder tissue so as to provide rationales for preventing and treating neurogenic bladder.MethodsA total of 70 female Wistar rats were divided randomly into three groups of bladder outlet obstruction （A, n=30）, nerve damage （B, n=20） and control （C, n=20）. At Days 10 and 30 postoperatively, 10 rats were randomly selected from each group for urodynamic examinations. Then bladders were resected and weighed. All bladder specimens received a serial process of hematoxylin ＆ eosin （HE） staining and immunohistochemistry. The changes and the expression of CTGF in bladder wall were observed under a microscope.ResultsUrodynamics, Group A： at Days 10 and 30 postoperatively, bladder capacity and pressure of detrusor were significantly higher than those of group C at the same timepoints （P〈0.05）. All compliance were all less than that of group C. Group B： at Days 10 and 30 postoperatively, bladder capacity and compliance were significantly more than those of group C （P〈0.05）. However, the pressure of detrusor was less than that of group C at the same timepoints （P〈0.05）. HE staining： Group A： bladder walls were thicker than normal. Inflammatory cell infiltration and hypertrophy of smooth muscle cells with bigger nucleus and hyperchromatic cytoplasm were observed. Group B： bladder walls were not thicker or thinner than before. Smooth muscle cells were disarranged. Prominent infiltration of inflammatory cells was observed. Immunohistochemistry of CTGF. Group A： marked hyperchromatism was present in layers of smooth muscles and transitional epithelia. Deposition of large brown particles was found in smooth muscle cells. The expressions of CTGF were significantly higher at Day 10 （81.86±4.40） and Day 30 （127.32±9.37） than those of control groups a

关 键 词：神经源性膀胱 顺应性 胶原纤维 

分 类 号：R726.9[医药卫生—儿科]