东方田鼠自发性卵巢癌的生物学特性  

Biological characteristics of spontaneous ovarian cancer in Microtus fortis

作　　者：周俊康 何天琼 文依信 刘倩 支文玲[1,2] 欧阳伶宣 祁雨珊 高鑫 周紫康 周智君[1,2] ZHOU Junkang;HE Tianqiong;WEN Yixin;LIU Qian;ZHI Wenling;OUYANG Lingxuan;QI Yushan;GAO Xin;ZHOU Zikang;ZHOU Zhijun(Department of Laboratory Animal Science,Xiangya School of Medicine,Central South University,Changsha 410013;Hunan Key Laboratory of Animal Models for Human Diseases,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅医学院实验动物学部,长沙410013 [2]人类重大疾病动物模型研究湖南省重点实验室(中南大学),长沙410013

出　　处：《中南大学学报(医学版)》2025年第1期11-22,共12页Journal of Central South University :Medical Science

基　　金：湖南省自然科学基金(2024JJ5422,2024JJ6494);长沙市重大科技专项(kh2301027)。

摘　　要：目的:在野生东方田鼠实验动物化培育过程中,9~15月龄东方田鼠在自然条件下能发生与人类上皮性卵巢癌相似的单一上皮性卵巢癌,但其病理类型和生物学特性尚不清楚。本研究对东方田鼠自发性卵巢癌的生物学特性进行分析,以期将东方田鼠发展成为人类上皮性卵巢癌的动物模型。方法:选取3只9~15月龄自发卵巢癌的雌性东方田鼠作为卵巢癌组,并选取与患病动物同窝的健康东方田鼠作为对照组。解剖2组东方田鼠,观察其卵巢病理变化;采用生化分析方法测定东方田鼠血常规和血液生化指标,苏木精-伊红(hematoxylin and eosin,HE)染色观察东方田鼠卵巢癌组织的病理变化,免疫组织化学染色检测卵巢癌常见免疫组织化学标志的蛋白质表达,实时反转录聚合酶链反应(real-time reverse transcription PCR,real-time RT-PCR)检测卵巢癌致病相关基因的转录水平。结果:东方田鼠自发性卵巢癌以双侧发病为主,肿瘤呈实性或囊实性;经HE染色及组织病理学分析,证实东方田鼠卵巢肿瘤来源为卵巢表面上皮组织。与对照组相比,卵巢癌组血红蛋白水平(P<0.01)、红细胞压积水平(P<0.05)、白蛋白水平(P<0.05)、血糖水平(P<0.01)显著下降,而淋巴细胞水平(P<0.05)、单核细胞百分比(P<0.05)、胆固醇水平(P<0.01)、孕酮水平(P<0.01)显著上升。卵巢癌组中卵巢癌致病相关基因ID3、CDC42、RHOA、RB1CC1、NF1、PIN1、MIB1、PDS5A、MCM7和MLH1表达均显著下调(均P<0.05),PAX8基因表达显著上调(P<0.05)。免疫组织化学染色结果显示WT1蛋白主要分布在整个细胞中,其在卵巢癌东方田鼠中表达水平相较于健康东方田鼠显著升高;肿瘤蛋白53(tumor protein 53,TP53)在健康东方田鼠和卵巢癌东方田鼠中均表达,分布在整个细胞中;而肝细胞核因子1β、孕激素受体蛋白在健康东方田鼠卵巢中高表达,在卵巢癌东方田鼠中表达水平显著降低,但均分布在�Objective:Wild-caught Microtus fortis(M.fortis)at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding,but its pathological types and biological characteristics remain unclear.This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M.fortis,intending to develop M.fortis as an animal model for human epithelial ovarian cancer.Methods:The female M.fortis(9−15 months old)with spontaneous ovarian cancer were selected as the experimental group,and healthy M.fortis from the same litter were selected as the control group.The ovarian pathological changes of the two groups were observed by dissection.Blood routine and biochemical indicators were measured by biochemical analysis.Hematoxylin and eosin(HE)staining was performed to observe the pathological changes in the ovarian cancer tissue of M.fortis.Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers,and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes.Results:Spontaneous ovarian cancer in M.fortis mainly affects both ovaries,with tumors appearing solid or cystic.HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium.Compared to the control group,the experimental group showed significantly decreased hemoglobin(P<0.01),hematocrit(P<0.05),albumin(P<0.05),and blood glucose levels(P<0.01),while lymphocyte percentage(P<0.05),monocyte percentage(P<0.05),cholesterol(P<0.01),and progesterone(P<0.01)levels were significantly increased.Expression of ovarian cancerrelated genes,including ID3,CDC42,RHOA,RB1CC1,NF1,PIN1,MIB1,PDS5A,MCM7,and MLH1,was significantly downregulated(all P<0.05),while PAX8 gene expression was significantly upregulated(P<0.05).Immunohistochemical results showed that Wilms’tumor gene 1(WT1)protein was mainly distributed throughout the cell,with signifi

关 键 词：东方田鼠 卵巢上皮癌 浆液性癌 免疫组织化学染色 基因表达 

分 类 号：R737.31[医药卫生—肿瘤]