CAJ | 학술논문

目的：探讨SD大鼠自发性乳腺肿瘤中线粒体凋亡通路相关因子的表达情况及作用机制。方法将130只（♀∶♂＝1∶1） Sprague-Dawley（ SD）大鼠于SPF屏障环境中饲养，收集大鼠自发性乳腺肿瘤组织，通过病理学检查对肿瘤进行定性并分类，分为3组：正常乳腺组织（I组），良性乳腺肿瘤组织（II组）和恶性乳腺肿瘤组织（ III组）。分别使用RT-PCR法和免疫组织化学法检测各样品中AIF、Cyt C、APAF-1、caspase-3、XIAP的mRNA和蛋白的表达。结果130只大鼠中有14只检出自发性乳腺肿瘤，肿瘤发生率为10.77％；其中7只发生乳腺纤维腺瘤，7只发生乳腺癌，良、恶性肿瘤发生率均为5.38％。免疫组化结果如下，与 I组相比， II 组中 AIF、APAF-1、caspase-3蛋白表达显著降低（P＜0.01），Cyt C、XIAP蛋白表达显著增强（P＜0.01），Ⅲ组中AIF、Cyt C、APAF-1、caspase-3蛋白表达均显著减弱（P＜0.01），仅XIAP蛋白表达显著增强（P＜0.01）；与II组相比，III组中AIF、 Cyt C、caspase-3蛋白表达显著减弱（ P ＜0.01）， APAF-1、XIAP 蛋白表达显著增强（ P ＜0.01）。 RT-PCR 结果中，除APAF-1的mRNA与蛋白表达显著相关（P＜0.05），其余因子与免疫组化的结果极显著相关（P＜0.01）。结论乳腺肿瘤是SD 大鼠常见的肿瘤，线粒体凋亡通路相关因子AIF、Cyt C、APAF-1、caspase-3、XIAP 在乳腺肿瘤中的异常表达与肿瘤的发生发展密切相关。
목적：탐토SD대서자발성유선종류중선립체조망통로상관인자적표체정황급작용궤제。방법장130지（♀∶♂＝1∶1） Sprague-Dawley（ SD）대서우SPF병장배경중사양，수집대서자발성유선종류조직，통과병이학검사대종류진행정성병분류，분위3조：정상유선조직（I조），량성유선종류조직（II조）화악성유선종류조직（ III조）。분별사용RT-PCR법화면역조직화학법검측각양품중AIF、Cyt C、APAF-1、caspase-3、XIAP적mRNA화단백적표체。결과130지대서중유14지검출자발성유선종류，종류발생솔위10.77％；기중7지발생유선섬유선류，7지발생유선암，량、악성종류발생솔균위5.38％。면역조화결과여하，여 I조상비， II 조중 AIF、APAF-1、caspase-3단백표체현저강저（P＜0.01），Cyt C、XIAP단백표체현저증강（P＜0.01），Ⅲ조중AIF、Cyt C、APAF-1、caspase-3단백표체균현저감약（P＜0.01），부XIAP단백표체현저증강（P＜0.01）；여II조상비，III조중AIF、 Cyt C、caspase-3단백표체현저감약（ P ＜0.01）， APAF-1、XIAP 단백표체현저증강（ P ＜0.01）。 RT-PCR 결과중，제APAF-1적mRNA여단백표체현저상관（P＜0.05），기여인자여면역조화적결과겁현저상관（P＜0.01）。결론유선종류시SD 대서상견적종류，선립체조망통로상관인자AIF、Cyt C、APAF-1、caspase-3、XIAP 재유선종류중적이상표체여종류적발생발전밀절상관。
Objective To investigate the expression of AIF, CYT C, PAF-1, caspase-3, and XIAP in Sprague-Dawley rats with spontaneous mammary neoplasms.Methods One-hundred and thirty 3-4-week old SPF Spargue-Dawley rats (♀∶♂=1∶1) were fed in a specific pathogen free (SPF) breeding barrier for 60 weeks.The occurrence of spontane-ous breast tumors was recorded and histopathology was performed to identify the types of tumors.The rats were divided into 3 groups:rats with normal breast tissue ( group I) , with benign tumors ( group II) and with malignant tumors ( group III) . The expression of AIF, CYT C, APAF-1, caspase-3 and XIAP proteins and mRNAs were detected by immunhistochemistry ( IHC) and RT-PCR assay.Results Among these 130 SD rats, 14 rats were observed having spontaneous mammary neo-plasms with the incidence rate of 10.77%(14/130).In these neoplasm cases, 7 cases were mammary fibroadenomas, 7 cases of breast carcinoma, both with an incidence rate of 5.38%.Immunohistochemistry showed that, compared with the group I, the positive expressions of AIF, APAF-1, caspase-3 were decreased significantly (P<0.01), and the CYT C and XIAP expressions were significantly increased in the group II.The positive expression of all genes except XIAP was de-creased in the group III(P<0.01).Compared with the group II, APAF-1 and XIAP were significantly higher in the group III (P<0.01), and the positive expression of AIF, Cyt C, and caspases-3 were significantly decreased (P<0.01).In the results of RT-PCR assay, except APAF-1 which showed significant correlation with the results of immunohistochemistry ( P<0.05 ) , all the others showed an extremely significant correlation with immunohistochemical results ( P <0.01 ) . Conclusions Mammary tumors are most common spontaneous neoplasms in SD rats.Abnormal expression of mitochondrial apoptotic pathway-related factors AIF, CytC, APAF-1, caspase-3, and XIAP are correlated with the carcinogenesis and de-velopment of breast tumors.