摘要
清热止血宁是导师马宝璋教授在长期临床实践中总结出来的治疗血热型崩漏、月经过多的有效方剂。为了进一步探讨其止血的作用机制,本文选择的动物模型是以凝血功能调节模型、炎症模型、性腺轴及靶器官结构功能调节模型、子宫收缩活动调节模型等“模型组合”的形式,应用原位杂交、免疫组化、放射免疫、血清药理等实验技术方法进行了相关的实验研究,结果如下:
1.清热止血宁能缩短小鼠出凝血时间,缩短大鼠PT、APTT,提示其有多途径的促进凝血止血作用。
2.清热止血宁能抑制小鼠二甲苯所致的耳肿胀及大鼠子宫异物埋植所致的子宫炎症。
3.清热止血宁可加强子宫平滑肌收缩能力。
4.免疫组化结果表明,清热止血宁高剂量组能增强子宫内膜ET阳性表达。原位杂交结果表明,清热止血宁可以提高大鼠子宫ERα mRNA、PRmRNA的表达。
5.清热止血宁低剂量组能促进未成年大鼠卵泡发育、成熟、排卵和黄体生成,增加血清雌、孕激素水平。清热止血宁低剂量组对脏器系数有提升作用但不显著,而高剂量组对卵巢系数略有下调趋势,高、低剂量组对卵巢系数作用则有显著差异。说明清热止血宁对性腺轴可能具有一定的双向调节作用。
6.清热止血宁低剂量组能提高未成年大鼠血清FSH水平和LH水平,清热止血宁高剂量组有轻微抑制作用,高、低剂量组之间差异显著。
结论:清热止血宁具有多层次、多途径、多靶点的止血、调节及抗炎作用。
Qingrezhixuening is considered to be the effective recipe to treat metrorrhagia and menorrhagia due to blood-heat, which is summarized from long-term clinical practice by professor baozhang Ma. To discuss hemostatic mechanism of Qingrezhixuening, we select several experimental animal models to design "models association" and use technology of in situ hybridization, immunohistochemistry, serm pharmacology, radioimmunoassay to study. Result:1.Qingrezhixuening can decrease bleeding time,coagulation time and also decrease PT, APTT of rat,which shows it has mutiple-channels coagulation function.2.Qingrezhixuening depress ear swelling made by dimethybenzene-stimulating and the ueterine inflammation made by foreign material.3.Both of solution and pharmacological serm of Qingrezhixuening can increase the force of the contraction of the ueterine smooth muscle.4.High-dose of Qingrezhixuening can increase endothelin expression in endometrium; Qingrezhixuening can promote the mRNA expression of ER and PR in ueterin tissue with in situhybridization method.5.Low-dose of Qingrezhixuening can promote the development, maturity of follicle, and facilitate ovulation and the produce of corpus luteum, increase the E_2,P in serm of immature rat. It also improve ovarian coefficient while the high-dose decrease slightly, which shows the two groups have significant difference. It prove that Qingrezhixuening has two-way regulation on the function of HPOA.
引文
1.马宝璋.《中医妇科学》.上海科学技术出版社,第六版.1997.6
2.隋·巢元方.《诸病源候论》.南京中医学院校释.人民卫生出版社,1982.9:1062
3.清·陈梦雷.古今图书集成医部全录第九册.人民卫生出版社,1963.1:384
4.石冠清 武明钦主编.《黄帝内经·素问》选注.河南科学技术出版.1982.12:175
5.任英秋.《金匮要略语译》.上海科技出版社,1959.9:263
6.牛并占主编.中医妇科名著集成《妇人大全良方》.华夏出版社,1997.5:93
7.明·张介宾.《景岳全书》.上海科学技术出版社,1959.9:645
8.清·傅山.《傅青主女科》.上海人民出版社,1978.1:7
9.清·沈金鳌.《妇科玉尺》.上海科学技术出版社,1958.12:142
10.宋·赵佶.《圣济总录》.人民卫生出版社,1962.10:2471
11.牛并占主编.中医妇科名著集成《女科百问》.华夏出版社,1997.5:35
12.牛并占主编.中医妇科名著集成《万氏妇人科》.华夏出版社,1997.5:271
13.明·王肯堂.《女科证治准绳》.上海科学技术出版社,1959.12:37
14.清·傅山.《傅青主女科》.上海人民出版社,1978.1:23
15.任英秋.《金匮要略语译》.上海科技出版社,1959.9:285
16.元·朱震亨.《丹溪心法心要》.人民卫生出版社,1983.7:113
17.明·张介宾.《景岳全书》.上海科学技术出版社,1959.9:641
18.丛春雨.《近现代二十五位中医名家妇科经验》.中国中医药出版社,1998.6:114
19.金·刘完素.《素问病机气宜保命集》.中国古籍出版社,1998.5:180
20.张奇文主编.《妇科医籍辑要丛书月经病证》.人民卫生出版社,1995.9:262
21.隋·巢元方.《诸病源候论》.南京中医学院校释.人民卫生出版社,1982.9:1070
22.薛己.《薛氏医案选》.人民卫生出版社,1983.11:487
23.清·唐容川.《血证论》.上海人民出版社,1977.11:81
24.陈源生,郭铭信.谈谈崩漏辨证论治的几个问题.中医杂志,1979,(8):27
25.沈伯蕾,骆慧,朱龙禳.中医对妇女崩漏证的辨证治疗.上海中医杂志.1958,(5):17～19
26.何子淮.崩漏的辨证论治.中医杂志.1979,(11):28～29
27.丁仁甫.蔡小荪老中医诊治崩漏的经验.辽宁中医杂志.1985,(10):1
28.丛春雨.近现代二十五位中医名家妇科经验.中国中医药出版社.1998.6:114
29.隋·巢元方.《诸病源候论》.南京中医学院校释.人民卫生出版社.1982.9:1044
30.潘远根主编.中华医书集成第十五册.中国古籍出版社.1999.7:6
31.牛并占主编.中医妇科名著集成《万氏妇人科》.华夏出版社.1997.5:269
32.哈荔田.《哈荔田女科医案医话选》.天津科学技术出版社.1982.4:25
33.董素琴.中药治疗56例功能性子宫出血患者血液流变学观察.天津中医.1994,(3):13
34.李明英,邢建华,王庆兰.龙葵草合剂治疗功血临床及实验研究.中医药学报 1998,(4):36～38
35.金芳.功血饮对假孕大鼠下丘脑-垂体-卵巢轴功能的影响.中国实验方剂学杂志.1995,5(2):39～40
36.张晓东.功血灵颗粒治疗功血的实验研究.辽宁中医学院99级硕士论文
37.卫爱武.中药功血宁Ⅱ号冲剂对性腺轴作用机制的实验研究.天津中医学院97硕士论文
38.刘凤麒.传统中成药辨证治疗功血200例临床观察及机理研究.天津中医.2000,10(5):20
39.王玲,哈孝贤,屈彩芹,等.功血宁Ⅰ号冲剂对止血作用的影响.天津中医.2002,19(5):41
40.哈孝贤,等.中药功(更)血宁Ⅰ、Ⅱ号冲剂治疗功血的临床研究.天津中医学院学报.1990,(4):23
41.张娟.毛美蓉教授治疗崩漏的经验.国医论坛.1996,12(5):44
42.米延伟.裘笑梅老中医诊治崩漏的经验.黑龙江中医药.1988,(4):3
43.班秀文.崩漏证治梗概.江西中医药.1982,(1):23
44.丛春雨.近现代二十五位中医名家妇科经验.中国中医药出版社.1998.6:317
45.温光远.刘奉五老大夫对崩漏辩证分型治疗的经验.辽宁中医杂志.1983,(5):34
46.陈明见,陈文林.妇科名医郑兰芬临床经验探索.福建中医药.1992,(3):3
47.夏桂成主编.中医临床妇科学.人民卫生出版社.1994.9:3
48.肖琪薇.活血调经汤治疗置宫内节育器后月经过多102例.安徽中医学院学报.1994,13(3):18
49.陈民勤.马芩安胞汤治疗置环后月经过多98例.江苏中医.1996,17(2):15
50.郑其国.郑长松治疗月经先期的经验.辽宁中医杂志.1991,(2):14
51.李莉.班秀文治疗月经病经验撷萃.陕西中医.1993,14(6):260
52.黄瑛,达美君.专科专病名医临证经验丛书妇科病.人民卫生出版社.2002.1:48
53.康晴.夏桂成老师谈经间期出血症.陕西中医.1990,11(4):147
54.哈孝贤.小议“经间出血”.天津中医.1991,(4):3
55.代加莉,钟雪梅,黄凤书.云南白药治疗放环后月经量多经期延长38例.中国中医药科技.1999,6(6):4.9
56.薛永玲.沈仲理教授治疗子宫肌瘤的经验.陕西中医.1995,16(6):262
57.胡国华.朱南孙老中医治疗子宫肌瘤.天津中医.1992,(6):4
58.周翠珍.蔡小荪治疗妇科痼疾验方拾萃.江苏中医.1996,(17):9
59.王晓云.夏桂成用调周法治疗盆腔炎的经验.江苏中医.1999,20(11):6
60.黄瑛,达美君.专科专病名医临证经验丛书妇科病.人民卫生出版社.2002.1:3
61.陈少春,吕直.何子淮女科经验集.浙江科学技术出版社.1982,9:28
62.刘艳霞.郭志强教授治疗崩漏经验.中医教育.1998,17(5):59
63.罗明察.加减当归汤治疗崩漏47例.浙江中医杂志.1984,19(6):271
64.张从善,张天真.加减温经汤治疗崩漏的临床体会.河北中医.1985,(6):11
65.倪晓云.升陷汤加减治验崩漏.天津医药.1982,10(10):619
66.曹云霞.吴国栋老中医应用经方治疗崩漏的经验.广西中医药,1983,(5):1
67.汤叔良.古方新用治崩漏.中医杂志.1983,(3):20
68.王芳.针灸治疗崩漏40例临床观察.北京中医.1999,(2):44
69.于善堂,董庆华.针刺为主治疗崩漏38例.中国针灸.1999,(1):37
70.陈建平.头针治疗朋漏25例.浙江中医杂志.1995,(8):356
71.丁金榜,丁辉,施京红.神奇的幻火灸.陕西中医学院学报.2000,23(1):39
72.张继,龚建明.穴位注射止亡血敏治疗月经过多30例.山西中医.1997,13(5):32
73.刘佩云.针灸治疗月经过多症64例.陕西中医.2001,22(6):364
74.孙敬寿,王镇洲.针刺治疗经间期出血67例.针灸临床杂志.1997,13(12):15
75.张燕,姚锡珠.孕激素合中药人工周期治疗青春期功血30例临床观察.江西中医药.1995,(6):13
76.薛春柏,张素珍.中西医结合治疗更年期功血56例.江苏中医.1995,16(7):14
77.范利民.中西医结合治疗盆腔炎106例.实用中西医结合临床.2002,2(5):16
78.姜萍,赵莹,阮跃龙,等。中西医结合治疗子宫肌瘤70例疗效观察.现代中西医结合杂志.2003,12(7):707
79. Casey ML, MacDonald PC. The endothelin-parathyroid hormonerelated protein vasoactive peptide system in human endometrium: modulation by transforming growth factor-β. Hum Reprod, 1996, 11: 62—82
80. Strauss JF, Gurpide E. The endometrium: regulation and dysfunction. In Yen & Jaffe ed: "Reproductive Endocrinology". 3rded. Philadelphia: Saunders WBC, 1991. 314-319
81. Marsh MM, Findly JK, Salamonsen LA. Endothelin and menstruation Hum Repord, 1966,11:83-89
82. Salamonsen LA, Woolly DE. Matrix metalloproteinases in normal menstruation. Hum Reprod, 1996, 11: 124-133
83. Fraser IS, Hickey M, Song JY. A comparison Of mechanism underlying disturbances of bleeding caused by spontaneous dysfunctional uterine bleeding or hormonal contraception. Hum Reprod, 1996. 11: 165-178
84. Marsh MM, Findlay JK, Salamonsen LA. Endothelin and menstruation Hum Reprod, 1996, 11: 83-89
85. Li XF, Ahmed A. Dual role of angiotensionⅡ in the human endometrium. Hum Reprod,1996, 11:95-108
86. Pakarinen P, Luukkainen T, Laine H, et al. The effect of local intrauterine levonorgerstrel administration on endometrial thickness and uterine blood circulation. Hum Reprod.1995, 10: 2390-2394
87.隋龙,施永鹏.良性子宫出血性疾病的治疗.复旦大学出版社.2002.10:89
88.曹泽毅.中华妇产科学.人民卫生出版社.1999.6:1212
89. Balbi G, Piscitelliv, Di-Grazia F, et al. Acute plvic inflammatory disease comparison of the rapeutic protocols. Minerva Ginecol, 1996, 48: 19-23.
90.连利娟主编.林巧稚妇科肿瘤学.人民卫生出版社,第2版.1994,359
91. Rein MS. Friedman AJ, Barbieri RL, er al.Cytogenetic abnormalities in uterine leiomyomata. Obstet Gynecol, 1991, 77: 923
92. Kawafuchi K,Fujii S,Konishi I, et al. Ultrastructural study of cultured smooth muscle cells from uterine leioyoma and disease. Ann of Int Med, 1992, 116: 854
93.湖北中医学院主编.《中医妇科学》第一版.上海科学技术出版社.1980.5
94.浙江医学院二医院内科血液学实验室.小蓟凝血作用的实验研究.浙医通讯.1975,(5):22
95.刘凤鸣.中药蒲黄的药理学研究(三):大黄及其提取物对胶原诱导兔血小板聚集及解聚作用的影响.内蒙古药学.1989,8(2):5
96.盛瑞才,丁安伟,向谊.五种中药炒炭前后微量元素的含量研究.南京中医药大学学报.1995,11(2):96
97.杨耀芳,王钦茂,樊彦,筹.白芍总甙对大鼠血小板聚集的影响.安徽中医学院学报.1993,12(1):51
98.叶聚荣,林大杰,张丽华.地榆抗炎作用的药理研究.福建医药杂志.1985,(6):34
99.叶聚荣.地榆的抗炎作用.中药药理与临床.1985,(创):153
100.王斌,陈敏珠,徐叔云.白芍总甙对佐剂性关节炎大鼠的滑膜细胞功能及脾细胞增殖反应的影响.中国药理学与毒理学杂志.1994,8(2):128