【作者】 梁栋；

【导师】 宋爱莉；

【作者基本信息】 山东中医药大学 ， 中医外科学， 2008， 博士

【摘要】 目的：进行大鼠乳腺癌癌前病变结合肝郁证造模研究，观察大鼠在癌前病变病证结合造模阶段生物学行为、激素水平、血管生成等相关调控因子的改变，寻找癌前病变造模合理时间，健全乳腺癌癌癌前病变病证结合动物造模评价指标。方法：在中医理论的指导下，借鉴已有动物造模经验，采用二甲基苯蒽灌胃复制乳腺癌癌前病变大鼠模型，苯甲酸雌二醇和黄体酮肌注复制乳腺增生大鼠模型，夹尾激惹法复制肝郁证模型。实验大鼠随机分为空白对照组、二甲基苯蒽造模组、雌二醇造模组、二甲基苯蒽加夹尾造模组、雌二醇加夹尾造模组。实验开始后定期观察大鼠生物学行为的变化，在第8周、第12周分批活杀实验大鼠，观察各组大鼠乳房外形、5-羟色胺和乳腺组织形态改变，以及乳腺组织VEGF、Ki67、CD34、P63、C-erbB-2的免疫组化表达改变。结果：1、病证结合造模两组大鼠与单纯疾病造模两组大鼠比较，一般行为更符合肝郁证特点(P〈0．01)，5-羟色胺检测有显著差异(P〈0．01)；2、在组织形态方面，第8周二甲基苯蒽加夹尾造模组癌前病变出现率明显高于二甲基苯蒽造模组(P〈0．05)，第12周二甲基苯蒽加夹尾造模组与二甲基苯蒽造模组癌前病变和肿瘤出现率无显著差异(P〉0．05)，但均明显高于雌二醇造模组和雌二醇加夹尾造模组(P〈0．01)；3、免疫组化检测，二甲基苯蒽加夹尾造模组、二甲基苯蒽造模组VEGF、Ki67、C-erbB-2、CD34、P63表达与雌二醇造模组、雌二醇加夹尾造模组有显著差异(P〈0．01)，两组内免疫组化表达无显著差异(P〉0．05)。结论：二甲基苯蒽灌胃加夹尾激惹能成功复制大鼠乳腺癌癌前病变肝郁证模型。该模型大鼠的一般行为、神经内分泌表现符合中医肝郁证特点。这种病证结合造模方法能影响增殖细胞核抗原、血管内皮生长因子、原癌基因的表达，缩短癌前病变动物造模时间，提高造模成功率。同时，研究证实了CD34、P63表达对乳腺良恶性病变的鉴别作用，为评判乳腺癌癌前病变动物造模是否成功提供了可靠指标。更多还原

【Abstract】 Objective:according to investigate the animal pattern of the depression syndrome ofthe liver breast precancerous,records breast precancerous change from the view ofangiogenesis,the hormone levels,in order to find a reasonable time to induction breastprecancerous in rats,and to provide a objective criterion for about breast precancerousmodel combining syndrome with disease in rats.Methods:combining the TraditionalChinese Medicine theory to experience of establish models,animal pattern of breastprecancerous was made by DMBA gavage,animal pattern of HMG was made by estroneand progesterone injection.stagnation syndrome of the liver modle was made by Jire law.Rats were randomly divided into 5 groups:the control group,the DMBA group,theestrone group,the DMBA folder tail group,the estrone folder tail group,these groupswere treated with different drugs.after 8 and 12 weeks,observing the shape of breast,microcirculation,5-HT,pathological changes of breast tissue,and the expression ofVEGF、Ki67、CD34、P63、C-erbB-2 by immunohistochemistry.Results:1、in the generalconduct,the comparative group more anastomosis the depression of the liver type to thetwo groups of the animal pattern(P〈0.01),there was significant difference (P〈0.05) inthe microcirculation and 5-HT;2、In the organization and morphology,after 8 weeks,theDMBA group’s rate of breast precancerous higher than the DMBA folder tail group,after12 weeks,the DMBA group and the DMBA folder tail group is same (P〉0.05) in the rateof breast precancerous and canner occurrence,but higher than the estrone group and theestrone folder tail group(P〈0.01) 3、in Immunohistochemistry,the expression of VEGF、Ki67、C-erbB-2、CD34、P63 is difference in the DMBA groupand the DMBA folder tail group(P〈0.01),the two group is same repreat(P〉0.05).Conclusion:It is an successful method to induce animal pattern of thedepression of the liver type breast precancerous by gavage method and jire law.performance of general conduct、microcirculation、neuroendocrine are anastomosis withclinical features of stagnation of the liver type.the methods is to impact proliferating cellnuclear antigen,VEGF,expression of oncogene,shorten time about establish all models ofdisease,improve success rate.in addition,the study proved the expression of CD34 andP63 can differentiate Benign and malignant breast lesions,and provided reliable indicatorfor evaluating whether the animal pattern of breast precancerous is successful.更多还原