目的 :通过建立人乳腺癌MCF-7裸鼠移植瘤模型,研究肿瘤化疗中组织氧分压(partial pressure of oxygen,PO2)值的变化,并初步分析其形成的原因。方法 :将人乳腺癌MCF-7细胞接种于BALB/c-nu/nu裸小鼠建立移植瘤模型,同时将Lipc探针植入肿瘤组织,通过电子顺磁共振(electron paramagnetic resonance,EPR)技术检测肿瘤生长时肿瘤组织中PO2的水平。于监测的第4周开始腹腔注射多柔比星(doxorubicin,ADM),通过EPR持续监测化疗期间肿瘤组织中PO2的变化规律;并于化疗后的第4天时采用分光光度法检测各组小鼠肿瘤组织中线粒体酶(还原型烟酰胺腺嘌呤二核苷酸脱氢酶、细胞色素C氧化酶和琥珀酸-细胞色素C还原酶)的活性;利用激光多普勒血流探测仪检测肿瘤组织在化疗前后肿瘤局部血流量(regional blood l ow,RBF)的变化情况。结果 :EPR对肿瘤中PO2的持续监测发现,肿瘤在生长过程中,其组织中的PO2逐步升高,至第4周时PO2形成峰值,随后逐步下降。化疗后肿瘤组织中的PO2至给药后第4天时达峰值水平,随后PO2逐步降低。对移植瘤组织中线粒体活性的检测结果提示,化疗后肿瘤组织中还原型烟酰胺腺嘌呤二核苷酸脱氢酶、细胞色素C氧化酶和琥珀酸-细胞色素C还原酶的活性均较化疗前显著下降。肿瘤RBF监测结果提示,化疗后初期的肿瘤RBF较化疗前无明显变化,但化疗中后期的RBF较化疗前显著减少。结论 :EPR氧测定技术实现了对实体瘤化疗时组织微环境PO2的持续监测,ADM对肿瘤组织中线粒体活性和RBF的改变可能是影响PO2变化的主要作用机制。 OBJECTIVE: To establish a model of human breast cancer MCF-7 xenografts in nude mice to study the changes of tissue partial pressure of oxygen (PO2) in tumor chemotherapy and to analyze the causes of the formation. Methods: Human breast cancer MCF-7 cells were inoculated into nude mice BALB / c nu nu mice to establish a xenograft tumor model. At the same time, Lipc probe was implanted into the tumor tissue. Electron paramagnetic resonance (EPR) The level of PO2 in the tumor tissue was measured during tumor growth. At week 4, doxorubicin (ADM) was injected intraperitoneally. The changes of PO2 in tumor tissue were monitored continuously by EPR. On the fourth day after chemotherapy, the mice in each group were detected by spectrophotometry The activities of mitochondrial enzymes (reduced nicotinamide adenine dinucleotide dehydrogenase, cytochrome C oxidase and succinate-cytochrome C reductase) in tumor tissue were measured. Tumor tissues were detected by laser Doppler flowmetry The changes of tumor blood flow (RBF) before and after chemotherapy. Results: The continuous monitoring of PO2 in the tumor by EPR showed that the PO2 in the tissue increased gradually during the growth of the tumor, and peaked at the 4th week, then decreased gradually. PO2 in tumor tissue after chemotherapy reaches peak level on the 4th day after the administration, and then PO2 gradually decreases. The results of mitochondrial activity in transplanted tumor tissue suggest that the activity of reduced nicotinamide adenine dinucleotide dehydrogenase, cytochrome C oxidase and succinate-cytochrome C reductase in tumor tissue after chemotherapy is higher than that of chemotherapy Before the significant decline. The results of RBF monitoring showed that there was no significant change of RBF in the initial stage of chemotherapy after chemotherapy, but the RBF in the middle and late stage of chemotherapy was significantly lower than that before chemotherapy. CONCLUSION: EPR-Oxygen determination can continuously monitor the tissue microenvironment of PO2 during solid tumor chemotherapy. The changes of mitochondrial activity and RBF in tumor tissue may play a major role in the changes of PO2.