【作者】 李静蔚；

【导师】 宋爱莉；

【作者基本信息】 山东中医药大学 ， 中医外科学， 2005， 博士

【摘要】 目的:从血管生成角度深入探索认识乳腺增生病疾病本质,为中医辨证分型及疗效标准的确立提供客观化指标,为中医药治疗乳腺增生病及抑制/逆转癌变提供基础理论依据。动物实验探索并制作肝郁血瘀型乳腺非典型增生病病证结合动物模型,进一步认识乳腺增生病与血管生成因子表达的关系,并从血管生成角度探讨中药乳复汤干预治疗乳腺非典型增生病、预防其癌变的作用。方法:临床研究收集140例肿块明显乳腺增生病患者,微创活检后,免疫组化法观察不同中医证型乳腺组织的病理形态学改变及VEGF、bFGF、MVD表达情况。动物实验首次采用灌服二甲基苯并蒽加佩戴颈部枷具的方法制作病证结合动物模型,并用中药乳复汤治疗,平消片对照治疗,观察各组大鼠乳腺组织的病理表现以及VEGF、bFGF、MVD的表达情况。结果:临床研究显示痰瘀互结型较肝郁气滞型、冲任失调型乳腺增生病变程度重(P<0.01),血管生成因子表达程度高(P<0.05);组织血管生成活性与增生程度密切相关,随增生程度加重,血管生成因子MVD、VEGF、bFGF表达增强(x~2=118.0090,P<0.0001);非典型增生的的MVD及VEGF、bFGF表达高于一般增生(P<0.01)。实验研究显示:病证结合动物模型较单纯疾病模型增生程度高(P<0.05),血管生成因子表达强(P<0.05);乳腺非典型增生的MVD及VEGF、bFGF表达高于一般增生(x~2=31.3827,P<0.0001);乳复汤能降低大鼠乳腺增生病理改变程度,减轻VEGF、bFGF、MVD的表达强度,效果优于平消片组(P<0.05)。结论:乳腺非典型增生病临床多辨证为痰瘀互结型,血管生成因子表达程度高,提示病理类型和血管生成因子表达可作为中医临床辨证指标之一。病证结合造模方法更符合中医药实验要求;乳复汤具有抑制血管生成、干预/阻断乳腺非典型增生的作用,为中医药研究提供新的实验方法和治疗思路。更多还原

【Abstract】 OBJECTIVE: A study was conducted to determine the essence of mammary hyperplasia from the view of angiogenesis, in order to provide a criterion for Tradional Chinese Medicine (TCM)types and curative effect. And to discuss the relation between mammary atypical hyperplasia and angiogenesis based on disease-syndrome animal models test. METHODS: 140 patients of mammary hyperplasia chosen in random were grouped into three in TCM types, and were observed their pathology ,and the expression of VEGF bFGF MVD after biopsy. The animal models of mammary atypical hyperplasia with liver-stagnation and blood-stasis syndrome were induced for the first time on irrigating 7,12-demethylbenz[a] anthrancene + neck-shackles. Part of rats were treated by rufutang-herb. Then to observe the pathological character and the expression of MVD,VEGF,bFGF in rats’ breasts. RESULTS: The pathology grade and the expression of VEGF bFGF MVD were different in three types (P<0.01).The phlegm-stasis type is more propotion of etypital hyperplasia, more counts of MVD, and higher expression of VEGF, bFGF than the liver-stagnation type and the chong-ren-disorder type (x2=l 18. 0090, P<0. 0001). And that of atypical hyperplasia is more than general hyperplasia (P<0. 01). Atypital hyperplasia rate and expression degree of MVD, VEGF, bFGF in disease-syndrome-model group is higher than disease-model group(P<0.05). And the expression of MVD, VEGF, bFGF in atypical hyperplasia is higher than general hyperplasia(x2=31.3827, P<0.0001). Rufutang-herb can depress the degree of pathological change and expression of MVD, VEGF, bFGF, and its effection is precede to pingxiaopian-capsule.CONCLUSION: Most of mammary atypical hyperplasia are phlegm-stasis type,and the expression of angiogenesis factors is higher. Pathological characters and expression of VEGF bFGF. MVD can be considered the criterion in studying the TCM更多还原