中文摘要：

目的 建立不同类型无神经节细胞巨结肠乳鼠实验动物模型，为进一步研究该病的发病机制及相关分子生物学机制提供可靠模型。方法 将6～8日龄 SD 大鼠4窝（每窝10只乳鼠）随机分为实验组（包括短段型组、常见型组、长段型组）及对照组。对照组乳鼠经肛门推注9 g/L盐水，实验组分别采用经肛门置入不同长度的导管，推注不同剂量、不同浓度苯扎氯铵（BAC）的方法进行处理。分别于处理后2、4、6、8周行大体观察，取全段结肠及直肠，固定、包埋、切片后行 HE 染色，通过免疫组织化学染色检测蛋白基因产物9.5 （PGP9.5）的表达以鉴定模型建立成功与否，确定病变累及肠管的范围。通过免疫荧光技术观察狭窄肠段与相应部位正常肠段c-kit标记的Cajal间质细胞（ICC）的表达。结果 实验组大鼠处理后4周逐渐出现腹胀，粪便颗粒变小。8周处死后解剖发现肠管出现痉挛狭窄，狭窄近端粪便潴留；组织学检查可见处理段肠管肠神经节细胞基本消失，且不同的实验处理方法造成病变累及的肠段明显不同。对照组无上述改变。与对照组相比，实验组c-kit标志的ICC在狭窄段的表达明显减少。结论 经肛门灌注不同浓度、不同剂量BAC的方法成功建立了短段型、常见型、长段型3种类型无神经节细胞巨结肠的乳鼠实验模型，该方法建立的模型稳定、可重复性好，为深入研究先天性巨结肠的发病机制提供了一个可靠的模型基础。

英文摘要：

Objective To establish neonatal rat models with Hirschsprung＇s disease（HD） ,and to provide the experimental basic for a future study on pathogenesis of HD. Methods Four litters neonatal SD rats of 6 to 8 days old were randomly divided into 4 groups （ 3 experimental groups including short-segment, recto-sigmoid, long-segment HD and a control group）. Different lengths of microinjection catheters were carefully placed into the bowl ,and different do- ses and concentrations of benzalkonium chloride（BAC） were injected to establish 3 types of HD animal models. After treatment with BAC, animals were sacrificed and examined for general observation at postoperative 2,4,6 and 8 weeks. After dehydration, the samples including the whole colon and the rectum, were embedded in paraffin and farther pro-cessed into 5 μm-thick sections for hematoxylin-eosin （ HE ） staining. Immunohistochemical analysis of protein gene product 9.5 （ PGP9.5 ） was conducted to further confirm the animal model establishment and to determine the extent of lesion involvement. The expression of c-kit labeled interstitial cells of eajal （ ICC ） in the narrow segment was detected with and then compared with the controls. Results After 4 weeks of BAC treatment,rats in the ex- perimental groups gradually exhibited the symptoms of abdominal distension, and smaller fecal particles. Autopsy revealed a narrow segment accompanied with distended proximal colon filled with massive feces. Histological examina-tion showed the lack of ganglion cells within the area of BAC treatment. And the different methods caused significant differences in the degree of lesion in the bowel. No visible change in the bowels was observed in the control group. Com- pared with the normal controls, the expression of c-kit labeled ICC in the narrow segment was significantly reduced. Conclusions Peranum application of different doses and concentrations of BAC successfully produced short-segment, recto-sigmoid,long-segment aganglionic bowel in the neonatal rats. T