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良性胆管狭窄、硬化性胆管炎和胆管癌的动物模型以及表皮生长因子受体在导管增殖中的作用。

An animal model of benign bile-duct stricture, sclerosing cholangitis and cholangiocarcinoma and the role of epidermal growth factor receptor in ductal proliferation.

作者信息

Cheifetz R E, Davis N L, Owen D A

机构信息

Department of Surgery, University of British Columbia, Vancouver, BC.

出版信息

Can J Surg. 1996 Jun;39(3):193-7.

PMID:8640617
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3950005/
Abstract

OBJECTIVE

To adapt an animal model of benign bile-duct stricture, sclerosing cholangitis and cholangiocarcinoma in order to determine if the expression of epidermal growth factor receptor (EGFr) could be used to differentiate these lesions.

DESIGN

A prospective control study with blinded interpretation of liver biopsy histology and immunohistochemical staining as the criterion standards.

SETTING

A university-affiliated research centre.

SUBJECTS

Male Syrian Golden hamsters (40 for benign duct stricture, 29 for sclerosing cholangitis and 27 for cholangiocarcinoma).

INTERVENTIONS

Ligation of the common bile duct with 6-0 catgut for benign duct stricture; injection of the biliary tree with 0.15 mL of formalin for sclerosing cholangitis; and weekly subcutaneous injections of 500 mg/kg of di-isopropanolnitrosamine for 10 weeks followed by ligation of the common bile duct with 6-0 catgut for cholangiocarcinoma. Routine histologic preparation of liver biopsies obtained at autopsy 10 weeks postoperatively then immunohistochemical staining of specimens for EGFr.

MAIN OUTCOME MEASURES

The development of benign or atypical biliary ductal proliferation, including adenoma and carcinoma formation. The presence or absence of immunohistochemical staining for EGFr.

RESULTS

Benign ductal proliferation without atypia was seen in 15 of 21 animals in the bile-duct-stricture group that were sacrificed, in 15 of 24 animals in the sclerosing cholangitis group and in 17 of 18 animals in the cholangiocarcinoma group. Atypical proliferation was seen in 13 of 18 animals with cholangiocarcinoma but not in the other two groups. The differential occurrence of atypical ductal proliferation was statistically significant (p < 0.00001) for both groups. No evidence of EGFr expression was found in any group.

CONCLUSION

Although the animal model was valid histologically for comparing benign and malignant biliary disease, EGFr does not play a role in biliary ductal proliferation and so cannot be used to differentiate between benign and malignant lesions.

摘要

目的

改良一种良性胆管狭窄、硬化性胆管炎和胆管癌的动物模型,以确定表皮生长因子受体(EGFr)的表达是否可用于鉴别这些病变。

设计

一项前瞻性对照研究,以肝活检组织学和免疫组化染色的盲法解读作为标准。

地点

一所大学附属研究中心。

对象

雄性叙利亚金黄地鼠(40只用于良性胆管狭窄,29只用于硬化性胆管炎,27只用于胆管癌)。

干预措施

用6-0肠线结扎胆总管造成良性胆管狭窄;向胆管树内注入0.15 mL福尔马林造成硬化性胆管炎;每周皮下注射500 mg/kg二异丙基亚硝胺,持续10周,随后用6-0肠线结扎胆总管造成胆管癌。术后10周尸检时获取肝活检组织进行常规组织学制备,然后对标本进行EGFr免疫组化染色。

主要观察指标

良性或非典型胆管增生的发生情况,包括腺瘤和癌的形成。EGFr免疫组化染色的有无。

结果

在处死的胆管狭窄组21只动物中的15只、硬化性胆管炎组24只动物中的15只以及胆管癌组18只动物中的17只中可见无非典型性的良性胆管增生。在18只胆管癌动物中的13只可见非典型增生,而其他两组未见。两组非典型胆管增生的差异发生率具有统计学意义(p<0.00001)。任何一组均未发现EGFr表达的证据。

结论

尽管该动物模型在组织学上对于比较良性和恶性胆道疾病是有效的,但EGFr在胆管增生中不起作用,因此不能用于鉴别良性和恶性病变。

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