摘要
本研究主要总结了丘和明教授的血证学术思想和临床经验。丘和明教授从医五十年,在血证专业领域具有深厚的造诣和丰富的临床经验。丘和明教授博采众长,从《内经》、刘河间、朱丹溪、张景岳、以及温病学说得到启发,在血证临证中主张从火热论辨析血证病机,依从温病的卫气营血和三焦辨证理论,分析恶性血液病的病机,辨证时强调整体观和病证结合的思想。临证时注重阴阳平衡的治疗原则,推崇《血证论》止血、活血、宁血、补虚的四大法则。
丘和明教授临证中善于灵活应用中医基础理论,结合自身经验,开创了多种治疗血证的新方法新技术。丘和明教授创造性地将“肝藏血”理论阐述引申到血证临床,创立柔肝方治疗特发性血小板减少性紫癜,通过清肝、平肝、疏肝、养肝四法,促进肝藏血功能,减少血小板破坏,提高血小板水平。在多发性骨髓瘤的临证中,丘和明教授充分认识到了肾虚血瘀是多发性骨髓瘤的基本病机,建立了补肾活血治疗多发性骨髓瘤的基本法则,并创立补肾活血方,在临证中随症加减,提高多发性骨髓瘤疗效。对于再障的治疗,丘和明教授抓住了肾阴虚的实质,创立养阴补肾方,治疗再障,获得较好的效果。丘和明教授认为白血病的病机为邪实本虚,治疗应驱邪补虚并重,注重阴阳平衡。
本研究同时设计了应用丘和明教授的补肾活血方治疗多发性骨髓瘤的实验研究,实验研究采用随机对照的试验方法,把多发性骨髓瘤患者随机分为实验组、对照组,对照组仅予4-6个疗程化疗及支持治疗,实验组在化疗同时给予补肾活血方汤药口服,每次化疗服中药21天,六个月后评价骨髓缓解程度、β:-微球蛋白、淋巴细胞亚群和调节性T细胞水平的变化。骨髓缓解程度通过骨髓细胞形态学方法评价,淋巴细胞亚群和调解性T细胞的检测应用流式细胞仪的方法。结果显示,实验组获得了稍高的CR率、PR率和有效率,但是差异无统计意义,实验组治疗后的β:-微球蛋白较对照组减低明显,差异有统计学意义。实验组CD4+细胞较对照组升高,调节T细胞水平较对照组减低,差异有统计学意义。结论:补肾活血方能够降低多发性骨髓瘤肿瘤负荷,提高CD4+细胞水平,减低调节T细胞水平,改善免疫功能。
This study has two parts. Part one aims at a general summary on the academic thoughts and clinical experiences of Professor Qiu Heming on hemorrhagic syndromes. With nearly half century's medical practice, Professor Qiu developed profound academic achievements in medical research and got rich experiences in treating hemorrhagic syndrome.
His academic achievements rooted deeply from classical works of Chinese traditional medicine and theories of other medical masters in history such as Canon of Huangdi, Liu Hejian, Zhu Danxi, Zhang Jingyue, and theory of warm disease school.
During the clinical practice on hemorrhagic syndrome, Professor Qiu believes that fires act as important reasons for hemorrhagic syndromes. He always uses three energizer differentiation method and wei-qi-ying-xue methods to differentiate hemorrhagic syndrome besides ba-gang principles. Professor Qiu emphasize entirety conceptions in the differentiation process, he always takes syndromes and diseases together into differentiation. He always takes it carefully to balance the two sides of yin and yang during the treatment for hemorrhagic syndromes. He also give high praise to the treatise on hemorrhagic syndromes an famous classical medical work by Tang Rong-chuan who first established the four major hemostatic methods which are to stop bleeding, to dissipate coagulation, to cool down circulation and to reinforce sufficiency.
Professor Qiu is very expert at applying basic principles of Chinese medicine in the complicated clinical problems. With his profound experiences of medical practice he developed many new theories and new methods for hemorrhagic syndromes. Professor Qiu creatively applied the principle about the liver's holding blood in the treatment of idiopathic thrombocytopenic purpura (ITP). He found that ITP was caused by liver's incapacity to hold blood, so he use methods of soothing liver, nourishing liver, pacifying liver and clearing liver to treat ITP to promote the liver's blood holding ability and to decrease the damage of platelets. This method gets very good results in elevating platelets level.
Professor Qiu believes that insufficiency of kidney and hemostasis are responsible for the development of multiple myeloma, so he created a herbal formula of Bushen Huoxue Fang to promote the curing efficacy for multiple myeloma. He also created an Yangyin Bushen formula for aplastic anemia (AA) with his accurate understanding about the focal pathological lesion in AA which is the yin deficiency of kidney. Professor Qiu believes that excessive pathogens and insufficient essences are both important in the development of leukemia, so he insists that expelling external pathogens and supplying inner insufficiencies play the same important roles in curing leukemia.
The second part of this study is about the clinical and laboratory researches on multiple myeloma(MM) treated with bushen huoxue fang.
This study applies random and control methods. About22Patients with MM were allotted into experiment group and control group, all the patients of the two groups were treated with the M2chemotherapy regimen for4to6cycles which lasted nearly half a year. The patients in experiment group were applied with oral decoction of bushen huoxue fang daily for21days per cycle lasting for half a year. At the end of treatment, all patients were tested on bone marrow cellularity, serial β2-microglobulin and lymphocytic subgroups including the regulatory T cells (CD4+CD25+Treg). The results show that the experiment group has higher CR rate, PR rate and effective rate than the control group but with no statistical significance. The serial β2-microglobulin level in experiment group is higher than that in control group with statistic significance. The lymphocyte analysis shows higher levels of CD4+T and CD4+CD25+Teg in experiment group than in control group with statistic significance. So it is concluded that bushen huoxue fang is effective in treating MM to reduce tumor burden and increasing CD4+T cells and decreasing regulatory T cells which means the immune function will be intensified.
引文
[1]黄礼明.急性白血.病阴液病变及其治疗探讨[J].中国医药学报,2004,19(6):375-377.
[2]黄礼明,丘和明.试论卫气营血、三焦理论在急性白血病辨治中的应用[J].中医杂志,200445(5):395-396.
[3]黄礼明,胡莉文.丘和明教授以青篙鳖甲汤治疗血.液病验案[J].新中医,2004,36(7):7-8.
[4]胡莉文,黄礼明,丘和明.中医论治急性白血病山血探讨[J].中华中医药杂志,2005,20(8):484-485.
[5]匡荣仁.从肝肾论治特发性血小板减少性紫癜一例[J].中外健康文摘,2007,10:59-60
[6]杨振江,张惠臣,丘和明.从“干血劳”辨治骨髓增生异常综合征[J].河南中医药学刊,2000,15(6):2-4
[7]李振波.清毒饮和养正片对环磷酰胺所致造血抑制小鼠系造血功能的影响[J].中国中医药科技,1995,6(4):261-262
[8]陈鹏.试论肝藏血.理论的临床意义[J].新中医,2011,43(2):10-11.
[9]蓝海,刘安平,占学奎等.丘和明治疗原发性血小板减少性紫瘫经验[J].中医杂志,2011,52(6):462-463.
[10]陈鹏,丘和明,宋爽等.补肾活血法辅助化疗治疗多发性骨髓瘤骨病16例疗效观察.新中医,2006,38(8):24-26.
[11]任荣政,鞠立霞.周永明治疗多发性骨髓瘤经验[J].中医杂志,2007,48(4):306-7.
[12]汗学友.中西医结合治疗多发性骨髓瘤21例观察[J].浙江中西医结合杂志,1996,(1):16.
[13]胡荫奇 常志遂.痹病古今名家验案全析[M].北京,2006年1月,科学技术文献出版社第一版,189-190.
[14]李秋柏、游泳、陈智超等.黄连解毒汤抑制多发性骨髓瘤RPM18226细胞增生及促进凋亡作用的研究[J].白血病.淋巴瘤,2006,15(6):412-415.
[15]苏风哲.中医药治疗多发性骨髓瘤临床探讨[J].世界中西医结合杂志,2007,2(9):551-2.
[16]薄兰君、陈毓华.雷氏丹参片联合化疗治疗多发性骨髓瘤疗效观察[J].中成药,2006,28(7):992-3.
[17]严鲁萍.中西医结合治疗发现骨髓瘤18例疗效观察[J].贵阳中医学院学报,1995,17(3) :39.
[18]魏学礼,马兰,蒋楠等.多发性骨髓瘤证治体会[J].天津中医药,2007,24(1):75.
[19]陈健一,李晓惠,孔祥图等.扶正解毒活血方合用亚砷酸注射液治疗难治性多发性骨髓瘤30例[J].河北中医,2007,29(11):1009-10.
[20]李新成.雄黄联合六味地黄丸治疗多发性骨髓瘤临床观察[J].湖北中医杂志,2007,29(3):33.
[21]李世辉、潘岐、薛芳等.青蒿琥酯对SP2/O骨髓瘤细胞的强效增生抑制及促进凋亡作用[J].中成药,2007,29(3):434-435.
[22]刘波、白庆咸、陈协群等.姜黄素对人多发性骨髓瘤细胞的抑制作用及其机制[J].肿瘤,2008,28(12):1051-54.
[23]马明信.多发性骨髓瘤经生胡萝卜汁治疗长期缓解1例[J].中华内科杂志,1993,32(9):609.
[24]Woo EY, Chu CS, Golizt TJ. et al. regulatory CD4(+)CD25(+) T cells in tomors form patients with early stage non-small lung cancer and late stageovarian cancer[J]. Cancer Res.2001,61 (12):4766-4772.
[25]Caver TE, Slobod KS, Flynn PM, et al. Profound abnormality of the B/T lymphocytes ratioduring chemotherapy for pediatric acute lymphoblastic leukemia[J]. leukemia,1998, 12:619-622.
[26]Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum,1997,40:1725.
[27]袁劲,吴轲,徐逸等TGF2B1诱导CD4+CD25-T细胞分化为CD4+CD25+调节性T细胞[J].免疫学杂志,2007,23(6):5972598.
[28]Berden JH, Light R, van Bruggen MC, etal. Role of nucleosomes for induction and glomerulur binding of autoantibodies in lupus nephritis. Curr Opin Nephrol Hypertens, 1999,8:299-306
[29]Zhou W. Immunosuppressive networks in the tumor environment and their theraputic relevance[J]. Nat Rev Cancer.2005,5(4):263-274) (Shevach EM, diPaolo RA, Andersson J, et al. the lifestyle naturally occurring CD4+ CD25 FOXP3+regulatory T cells. [J]. Immunol Rev 2006,122:64-73.
[30]韩文敏,谢晓宝,邱国强等.多发性骨髓瘤患者外周血CD4+CD25high调节性T细胞的变化及意义[J].临床血液学杂志,2009,22(7): 361-364.
[31]杨宏光,天启,陈志雄等.中医辨证联合亚砷酸及沙利度胺治疗难治性多发性骨髓瘤临床观察[J].新中医,2009,41(8):69-70.
[32韩文敏,邱国强,周民等.多参数分析多发性骨髓瘤患者外周血.中CD4+CD25+调节性T细胞的表达[J],免疫学杂志,2009,25(3):326-33.
[33]Suarez A, Lopez P, Gomez J, etal. Enrichment of CD4 CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids[J]. Ann Rheum Dis,2006,65(11):151221517.
[34]章新奇,刘淑俊,张金芳等.多发性骨髓瘤辨证分型与T细胞亚群变化及肾功能损害关 系的研究[J].肿瘤,1998,18(6):425-427.
[35]房才龙,宗文九,范国荣等.肺癌患者辨证分型与外周血T淋巴细胞亚群和癌胚抗原的关系[J].中国中西医结合杂杂志,1995,15(7):405.
[36]游泳,王红祥,李秋柏等.参芪扶正注射液对急性髓系白血.病患者调节性T细胞作用的体外研究[J].中华肿瘤防治杂志,2006,13(22):1737-39.
[37]曹毅,庄亦仁.感染与细胞免疫[J].浙江临床医学杂志,2000,2(4):280-281.
[38]吕鸣,周晓青,孔宪涛.多发性骨髓瘤外周血T细胞亚群和B细胞相关免疫表型分析[J].武警医学,2003,14(1):20-22.
[39]陈银霞,刘捷,马肖容等.多发性骨髓瘤患者淋巴细胞亚群的检测及意义[J]. 现代肿瘤医学,2006,14(11):1434-35.
[40]孙理军,郝蕊,薛昶等.肾虚质大鼠CD_4~+CD_8~+T淋巴细胞亚群表达水平的研究[J].陕西中医,2008,29(12):1671-73.
[41]孙超越.肾虚质大鼠细胞因子和T淋巴细胞亚群表达水平及中药干预研究[硕十论文].陕西中医学院,2008,45-46.
[42]韩文敏,谢晓宝,邱国强等.多发性骨髓瘤患者外周血CD4~+CD25~-(high)调节性T细胞的变化及意义[J].临床血液学杂志,2009 22(7):361-2.
[43]张家玮.金匮肾气丸对金匮肾气丸证患者T淋巴细胞亚群的影响[J].北京中医,2002,21(1):52-53.
[44]薛克营,熊盛道,熊维宁等.丹参注射液对哮喘大鼠气道炎症及CD4+CD25+调节性T细胞的影响[J].华中科技大学学报(医学版),2008,37(1):18-19.
[45]王锦泳.宫颈原位癌的淋巴细胞亚群与中医证型的相关性研究[J].辽宁中医杂志,2008,35(5):644-655.
[46]钱会南.中医脾本质现代研究概况[J].中国中医药信息杂志,2002,7(9):85-87.
[47]周立峰,邱玉华,程钢等.圣愈汤对环磷酰胺诱导的免疫低下小鼠T细胞亚群和细胞因子的影响[J].现代实用医学,2009,21(8):808-813.
[48]汪晓燕.滋补肝肾、行气活血.类中药延缓线虫衰老的作用及分子机制研究[硕士论文].中国中医科学院,2010,
[49]黄智莉,于天启,戴微等.补肾强骨方联合化疗治疗多发性骨髓瘤15例疗效观察[J].新中医,2010,42(1):49-51.
[50]蒋楠.滋肝补肾解毒方治疗多发性骨髓瘤阴虚瘀毒型的临床研究[硕十论文]. 南京中医药大学,2006.
[51]黄玉燕.益气补肾活血方联合西医治疗多发性骨髓瘤的机制研究[硕十论文],北京中医药大学,2007.
[52]许晓倩,王健民,冯曹波等.急性髓细胞白血病和骨髓增生异常综合征患者血清β-2微球蛋白检测的临床意义[J].白血病.淋巴瘤,2006,15(1):27-29.
[53]马军,蒋金法.高血压合并冠心病患者血、尿β-2微球蛋白测定的临床意义[J].同济大学学报(医学版),2009,30(6):50-52
[54]贾利敏,吴迪.β-2微球蛋白检测在早期肾损害诊断中的意义[J].中国卫生检验杂志,2010,20(5):1116-17.