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目的观察无特定病原体(SPF)级雌性SD大鼠自发性乳腺肿瘤发生情况,探讨其生存的影响因素。方法对2008年1月至2012年5月间进行的5个慢性毒性合并致癌试验中对照组的400只SPF级雌性SD大鼠自发性乳腺肿瘤的发生情况进行分析。选取发生自发性乳腺肿瘤的大鼠36只,按照肿瘤性质分为良性乳腺肿瘤组18只(乳腺纤维腺瘤11只,乳腺腺瘤7只)和恶性乳腺肿瘤组18只(均为乳腺癌),计算肿瘤系数,采用免疫组织化学法检测其肿瘤细胞的增殖细胞核抗原(PCNA)蛋白的表达情况,分析大鼠生存的影响因素。结果 400只大鼠中有186只检出自发性乳腺肿瘤,肿瘤发生率为46.50%;其中173只发生乳腺纤维腺瘤,20只发生乳腺腺瘤,19只发生乳腺腺癌,肿瘤发生率分别为43.25%、5.00%和4.75%。恶性乳腺肿瘤组体质量低于良性乳腺肿瘤组(中位数:638.80 vs 571.30 g,P<0.05),PCNA蛋白阳性表达率高于良性乳腺肿瘤组(72.22%vs 22.22%,P<0.01)。2组肿瘤质量和肿瘤系数分别比较,差异均无统计学意义(P>0.05)。Cox比例风险回归模型分析显示肿瘤性质、肿瘤系数及PCNA蛋白表达强度是乳腺肿瘤生存的独立影响因素(P<0.05)。结论乳腺肿瘤是雌性SD大鼠常见的自发性肿瘤,恶性肿瘤、肿瘤系数越小、PCNA蛋白阳性表达强度越强者,大鼠生存时间相对较短,预后较差。
Objective To observe the occurrence of spontaneous mammary tumor in female Sprague - Dawley (SD) rats without specific pathogen (SPF) and explore its influencing factors. Methods The incidence of spontaneous breast tumors in 400 SPF female SD rats in the control group from January 2008 to May 2012 in five chronic toxicity carcinogenicity trials was analyzed. Thirty-six rats with spontaneous mammary tumor were selected and divided into benign breast tumor group (n = 11), breast adenoma group (n = 18) and malignant breast tumor group (n = 18) The tumor coefficient was calculated. The expression of proliferating cell nuclear antigen (PCNA) in tumor cells was detected by immunohistochemistry, and the influencing factors of survival were analyzed. RESULTS: Of the 400 rats, 186 were diagnosed as spontaneous breast tumors with a tumor incidence of 46.50%. Among them, 173 had breast fibroadenoma, 20 had breast adenoma and 19 had breast adenocarcinoma. The incidence of tumors were 43.25%, 5.00% and 4.75%. The body mass of malignant breast tumor was lower than that of benign breast tumor (median: 638.80 vs 571.30 g, P <0.05). The positive rate of PCNA protein was higher than that of benign breast tumor (72.22% vs 22.22%, P <0.01). There was no significant difference in tumor mass and tumor coefficient between the two groups (P> 0.05). Cox proportional hazards regression model analysis showed that the nature of the tumor, the tumor coefficient and the expression of PCNA protein were independent prognostic factors of breast cancer survival (P <0.05). Conclusions Breast tumor is a common spontaneous tumor and malignant tumor in female SD rats. The smaller the tumor coefficient, the stronger the positive expression rate of PCNA protein, the shorter survival time and the poorer the prognosis of the rats.