益气温阳中药方治疗荷MCF-7乳腺癌小鼠的实验研究
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摘要
论文根据传统中医理论,结合导师章永红教授长期研究诊治乳腺癌的学术思想,研究中医药对乳腺癌的理法方药的认识,并探讨了益气温阳法治疗乳腺癌的实验研究,通过观察益气温阳中药方对小鼠移植性荷MCF-7乳腺癌的影响,同时通过对文献的综合汇总,深入分析益气温阳中药方治疗乳腺癌的作用机制疗效。本文共分二个部分：
第一部分以理论研究为主,对癌症的现状,包括中国以至欧美等地,特别是乳腺癌作出了浅释,和现代中、西医学治疗乳腺癌的研究作了总结与综述,以扩大知识面、了解最新动态,为探索新的研究思路提供帮助,为以后的研究创造条件。再从理论上全面探讨乳腺癌的病因、病机及治法。认为乳腺癌的病因十分复杂,病因主要为外受寒气、湿邪、湿热等侵袭人体,加之饮食不节,脾胃损伤；或又因情志不调,肝气郁结,日久气滞寒凝而成积；或素体阳虚气虚,阴寒内盛,以致脾胃虚弱,湿邪内停,亦可影响气血运行,导致气滞血瘀湿阻而生积。乳腺癌的病位在乳腺,涉及肝、脾与肾,后期可影响五脏,病理性质为本虚标实,病理因素有气血不足、冲任失调,以至气滞、血瘀、痰凝、癌毒等多种病理因素,其中阳虚日久和阴寒内结不化是本病发病的根本,并提出气虚、阳虚、寒凝为乳腺癌的三大致病根元,癌毒内蕴是乳腺细胞癌变的病理基础,痰瘀蕴结是乳腺癌变的基本病理变化,阳气虚弱是乳腺癌发病的内在因素,提出益气温阳法,辅以化痰祛湿为其基本治疗方法。
第二部分以实验研究为主,采用人乳腺癌MCF-7细胞株小鼠动物模型,研究了益气温阳中药方治疗乳腺癌的作用。实验研究了中药组、西药组和中西医结合组共六组老鼠,治疗十天后杀鼠。观察小鼠症状、瘤体大小变化、表现、身材、活动、毛发等指标。结果显示益气温阳方能够改善症状,增强饮食和精神,加强小鼠抗肿瘤功能,提高小鼠的抑癌指数和从小鼠表现、身材、活动、毛发等未见中药方有毒性反应,但抑瘤疗效较西药环磷酰胺(CTX)组弱。荧光显微镜观察也发现中药治疗组小鼠肿瘤细胞核染色后,细胞零散、微绒毛少,染色质浓缩和核碎裂,细胞表面出现裂孔,可能与中药抗肿瘤作用有关。
Based on the theory of Traditional Chinese Medicine (TCM), combined with the Professor Zhang Yonghong academic ideas and experience in treatment of breast cancer, the thesis studies the theory of breast cancer treatment through the view of TCM and probe the influence of Strengthening Qi and Tonifying Yang decoction. Meanwhile the article collects and synthesizes the literature report to analyze the mechanism of Strengthening Qi and Tonifying Yang decoction. The thesis consists of two parts:
Part one is about reference of status of the cancer especially the breast cancer including China and Western regions. And the part is also to sum up Western medicine and TCM study. In this part the article reviews the status of experiment and clinical research for breast cancer in order to enlarge knowledge, probe out new trends, elucidate the existent question and view new research ideas, at the same time, the paper emphasizes the importance and necessary of deeper research. This part is also about research of basic theory which focuses on physiology and pathology of breast cancer and the relationship with other organs and discuss the etiology, pathogenesis and treatment methods. The article considers that the location of breast cancer lies in breast, mainly affect liver, spleen and kidney. The pathological character is Ben asthenia and Biao sthenia and the pathological factor is qi and blood deficiencies, chong and ren disorders, qi stagnation, cold coagulation, blood stasis, phlegm stagnation, and cancer toxin. Qi and Yang deficiencies and cold coagulation are pathogenic basis of breast cancer, phlegm stasis is the primary pathologic change, and asthenia of Qi and Yang is the internal pathogenesis. The article also put forward treatment principle of invigorating the Qi and Yang, and eliminating phlegm and damp as the basis.
Part two of this paper is about experimental research which studies the effect of Strengthening Qi and Tonifying Yang on the animal model of MCF-7breast cancer. The experiment studies the Chinese herbs, CTX, and combined treatment. The mice were killed after10days treatment, and the symptoms and effect were observed. The results show us that the Strengthening Qi and Tonifying Yang decoction can improve the symptoms such as the appetite and spirit, enhance the anti-cancer function, and increase the tumor suppressor index. From the observation of symptoms, no toxin are discovered from the herbs decoction. But the tumor suppressor rate is weaker than CTX. Scanning fluorescence microscopy shows Chinese herb group's tumor cell Nuclei chromatin condensation and nuclear fragmentation. Microvillus are smaller and there are hiatus on the surface of the tumor cell which may be caused by the effect of Chinese herbs anti-tumor function.
第一部分以理论研究为主,对癌症的现状,包括中国以至欧美等地,特别是乳腺癌作出了浅释,和现代中、西医学治疗乳腺癌的研究作了总结与综述,以扩大知识面、了解最新动态,为探索新的研究思路提供帮助,为以后的研究创造条件。再从理论上全面探讨乳腺癌的病因、病机及治法。认为乳腺癌的病因十分复杂,病因主要为外受寒气、湿邪、湿热等侵袭人体,加之饮食不节,脾胃损伤；或又因情志不调,肝气郁结,日久气滞寒凝而成积；或素体阳虚气虚,阴寒内盛,以致脾胃虚弱,湿邪内停,亦可影响气血运行,导致气滞血瘀湿阻而生积。乳腺癌的病位在乳腺,涉及肝、脾与肾,后期可影响五脏,病理性质为本虚标实,病理因素有气血不足、冲任失调,以至气滞、血瘀、痰凝、癌毒等多种病理因素,其中阳虚日久和阴寒内结不化是本病发病的根本,并提出气虚、阳虚、寒凝为乳腺癌的三大致病根元,癌毒内蕴是乳腺细胞癌变的病理基础,痰瘀蕴结是乳腺癌变的基本病理变化,阳气虚弱是乳腺癌发病的内在因素,提出益气温阳法,辅以化痰祛湿为其基本治疗方法。
第二部分以实验研究为主,采用人乳腺癌MCF-7细胞株小鼠动物模型,研究了益气温阳中药方治疗乳腺癌的作用。实验研究了中药组、西药组和中西医结合组共六组老鼠,治疗十天后杀鼠。观察小鼠症状、瘤体大小变化、表现、身材、活动、毛发等指标。结果显示益气温阳方能够改善症状,增强饮食和精神,加强小鼠抗肿瘤功能,提高小鼠的抑癌指数和从小鼠表现、身材、活动、毛发等未见中药方有毒性反应,但抑瘤疗效较西药环磷酰胺(CTX)组弱。荧光显微镜观察也发现中药治疗组小鼠肿瘤细胞核染色后,细胞零散、微绒毛少,染色质浓缩和核碎裂,细胞表面出现裂孔,可能与中药抗肿瘤作用有关。
Based on the theory of Traditional Chinese Medicine (TCM), combined with the Professor Zhang Yonghong academic ideas and experience in treatment of breast cancer, the thesis studies the theory of breast cancer treatment through the view of TCM and probe the influence of Strengthening Qi and Tonifying Yang decoction. Meanwhile the article collects and synthesizes the literature report to analyze the mechanism of Strengthening Qi and Tonifying Yang decoction. The thesis consists of two parts:
Part one is about reference of status of the cancer especially the breast cancer including China and Western regions. And the part is also to sum up Western medicine and TCM study. In this part the article reviews the status of experiment and clinical research for breast cancer in order to enlarge knowledge, probe out new trends, elucidate the existent question and view new research ideas, at the same time, the paper emphasizes the importance and necessary of deeper research. This part is also about research of basic theory which focuses on physiology and pathology of breast cancer and the relationship with other organs and discuss the etiology, pathogenesis and treatment methods. The article considers that the location of breast cancer lies in breast, mainly affect liver, spleen and kidney. The pathological character is Ben asthenia and Biao sthenia and the pathological factor is qi and blood deficiencies, chong and ren disorders, qi stagnation, cold coagulation, blood stasis, phlegm stagnation, and cancer toxin. Qi and Yang deficiencies and cold coagulation are pathogenic basis of breast cancer, phlegm stasis is the primary pathologic change, and asthenia of Qi and Yang is the internal pathogenesis. The article also put forward treatment principle of invigorating the Qi and Yang, and eliminating phlegm and damp as the basis.
Part two of this paper is about experimental research which studies the effect of Strengthening Qi and Tonifying Yang on the animal model of MCF-7breast cancer. The experiment studies the Chinese herbs, CTX, and combined treatment. The mice were killed after10days treatment, and the symptoms and effect were observed. The results show us that the Strengthening Qi and Tonifying Yang decoction can improve the symptoms such as the appetite and spirit, enhance the anti-cancer function, and increase the tumor suppressor index. From the observation of symptoms, no toxin are discovered from the herbs decoction. But the tumor suppressor rate is weaker than CTX. Scanning fluorescence microscopy shows Chinese herb group's tumor cell Nuclei chromatin condensation and nuclear fragmentation. Microvillus are smaller and there are hiatus on the surface of the tumor cell which may be caused by the effect of Chinese herbs anti-tumor function.
引文
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[2]范宇,傅西林,王颖,等.细胞凋亡及其相关基因与乳腺癌预后关系的研究[J].中国肿瘤临床,2000,27(7)：524-528.
[3]IWAYA K, TSUDA H, HIRAIDE H, et al Nuclear P53 immunoreaction Associated with poor prognosis of breast cancer [J]. Jap J Cancer Res,1991,82 (7):835-840.
[4]HITOSHIT, CHINAMIS, SHOICHIROT, et al A Prospective study of the significance of the gene and chromosome alteration as prognostic indicators of breast cancer patients with lymph node metastases [J]. Breast Cancer Res Treat,1998,48 (1):21-32.
[5]THOR AD, MOOR DH, EDGERTON SM, et al. Accumulation of p53 tumor suppressor gene protein: a independent marker of prognosis in breast cancer [J]. J Natl Cancer Inst,1992,84:845.
[6]幸天勇,杨金巧,周褚蕾.乳腺癌c-erbB (?)癌基因与雌,孕激素受体的关系及预后意义[J].中国普外基础与临床杂志,1999,6(1)：21.
[7]田秀娟,候恒,安晓燕.乳腺癌c-erbB-2的表达及其与组织学分级的关系[J].肿瘤研究与临床,2000,12(5)：318.
[8]石正,王秀荣,王少烽c-erbB-2(?)癌基因蛋自在乳腺肿瘤中的表达及其与预后的关系[J].临床与实验病理学杂志,1995,11(4)：296.
[9]HAINSWORTH P J, HENDERSON M A, STILLWELL R G, et al. Comparison of epidermal growth factor receptor, cerbB-2 product and ras p21 immunohistochemistry as prognostic markers in primary breast cancer [J]. Eur J Surg Oncol 1991,17 (1):9-15.
[10]Yoshida H, Kijima H, Terasaki Y, et al. Heterogenous expression of nm23 gene product as a predictor of lymph nodal status in human breast cancer [J]. Int J Oncol 1998,13 (6):1141-1146.
[11]HAUT M, STEEG P S, WILLSON JK, et al Induction of nm23 gene expression in human colonic neoplasms and equal expression in colon tumors of high and low metastatic potential [J]. J Natl Cancer Inst,1991,83:712-716.
[12]MAO H, LIU H, FU X, et al. Loss of nm23 expression predicts distal metastas is and poor survival for breast cancer [J]. Int J Oncol 2001,18 (3):587-591.
[13]HENNESSY C, HENRY JA, MAY FE, et al. Expression of the antimetastatic gene nm23 in human breast cancer:an association with good prognosis [J]. J Natl Cancer Inst,1991,83:281-285.
[14]Sage C, Agami R. Immense promises for tiny molecules:uncovering miRNA functions [J]. Cell Cycle, 2006,5 (13):1-7.
[15]Lin S L, Chang D, Wu D Y, et al. A novel RNA splicing mediated gene silencing mechanism potential for genome evolution [J]. Biochem Biophys Res Commun,2003,310 (33):754-760.
[16]Cummins JM, Velculescu V E. Implications of micro-RNA profiling for cancer diagnosis [J] Oncogene,2006,25 (64):220-227.
[17]Han J, Lee Y, Yeom K, et al. The drosha-GCR8 complex in primary microRNA processing [J]. Genes & Dev,2004,18 (24):3016-3027.
[18]Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing [J]. Nature, 2003,425 (6956):415-419.
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