乳腺癌癌前病变毒瘀互结模型研究

Study on the Syndrome Model of Poison Accumulated with Stasis of Precancerous Lesions of Breast Cancer

目的:通过乳腺癌癌前病变毒瘀互结证模型的研究,从大鼠一般行为学改变、舒肝颗粒药物干预两方面验证模型;并从组织病理学及免疫组化特点探讨模型预后。方法:SD大鼠分为空白组、对照组、模型组、舒肝颗粒组。用二甲基苯蒽(DMBA)联合长期慢性轻度不可预计应激制备乳腺癌癌前病变毒瘀互结模型,舒肝颗粒干预30 d。观察各组大鼠一般情况、肉眼肿瘤发生率、病理变化,免疫组化法染色观察各组大鼠血管内皮生长因子(VEGF)、趋化因子受体4(CXCR4)表达情况。结果:①与对照组相比,模型组大鼠出现一系列肝郁血瘀证的生物表征变化,且肉眼可见肿瘤发生率升高;②组织病理变化提示:模型组非典型增生较对照组数量增多,且程度加重。舒肝颗粒组大鼠病理以单纯增生伴局灶性轻度非典增为主,较模型组明显减轻。③免疫组化提示:模型组VEGF、CXCR4表达水平最高,较舒肝颗粒组明显升高,与对照组相比也有升高趋势。结论:长期慢性不可预计应激是大鼠毒瘀互结证形成的主要因素。对心理应激的干预,能延缓乳腺癌癌前病变的进一步发展。毒瘀互结证模型组VEFG、CXCR4表达明显升高,组织非典型增生程度较高,易转化成乳腺癌。

Objective：To validate the model from the aspects of common ethology change of rats and medicine of Shugan granule（soothing liver granule）,and further discuss the prognosis of the model according to the characteristics of histopathology and immunohistochemistry,through studying on the syndrome model of poison accumulated with stasis of precancerous lesions of breast cancer.Methods：SD rats were divided into the blank group,control group,model group and Shugan granule group.Syndrome models of poison accumulated with stasis of precancerous lesions of breast cancer were produced by a combination of DMBA with chronic mild unpredictable stress,and were intervened by Shugan granule for 30 days.Then general condition,macroscopic tumor incidence,pathological changes of rats in each group were observed through conventional methods.VEGF and CXCR4 expression of rats in each group were observed by the method of immunohistochemical staining.Results：①Compared with the control group,rats in the model group appeared series of organism changes of liver depression and blood stasis syndrome,and macroscopic tumor incidence increased;② Pathological changes showed that the quantity and severity of atypical hyperplasia in the model group both increased compared with the control group.Pathology of rats in the Shugan granule group mainly presented simplex hyperplasia accompanied with focal and mild atypical hyperplasia,which were obviously relieved compared with the model group.③ Immunohistochemistry showed that VEGF and CXCR4 expression levels in the model group were the highest,which were significantly higher than the Shugan granule group and also had increasing tendency compared with the control group.Conclusion：Chronic unpredictable stress is the major factor in forming the syndrome of poison accumulated with stasis.The intervention of psychological stress can delay the further development of precancerous lesions of breast cancer.VEFG and CXCR4 expressions in the model group with syndrome of poison accumulated with stasis significantly increase and atypical hyperplasia of tissue shows a higher degree,which can easily transform into breast cancer.