治疗更年期综合征常用中药雌激素样作用的实验研究

【作者】 王大伟；

【导师】 陈家旭；

【作者基本信息】 北京中医药大学 ， 中医诊断学， 2006， 硕士

【摘要】 更年期综合征是妇女由于卵巢功能衰退，体内分泌的雌激素水平明显下降，引起的心血管、神经、内分泌系统功能紊乱，导致功能性子宫出血、阵发性潮热和出汗、外阴及阴道萎缩、骨质疏松等症状及出现精神和植物神经系统的症状。随着我国人口结构不断的老龄化，该病有发病年龄提早、发病率上升的趋势，严重的影响了占妇女一生中1／3时间的围绝经期及绝经后期的健康问题和生活质量。 更年期综合征发病率较高，直接影响到更年期妇女的正常工作和生活，目前主要的治疗方法为激素替代疗法。雌激素是一种作用广泛的类固醇类激素，不仅对于女性生殖器官的发育及第二性征的保持具有不可替代的作用，而且对众多靶组织如生殖道、乳腺、骨骼及心血管系统生长发育功能有调节作用。雌激素替代疗法对减轻更年期妇女绝经期症状、防治骨质疏松有很好的效果。然而，长期激素替代疗法应用使子宫内膜癌的患病风险增加。与孕激素联合应用的激素替代疗法，虽然能减少这种风险，但乳腺癌及心脑血管病的发病风险增加，雌激素在临床长期应用所带来的不良反应一直困扰着人们。 植物雌激素是一类存在于植物中、与雌激素结构相类似的生物活性物质，它能与雌激素受体结合，并且具有双向调节作用。它能抑制雌激素依赖性肿瘤的生长，减轻更年期综合征。近来植物雌激素作为雌激素的替代品，以其安全性及显著的疗效，受到越来越多的关注。中草药在我国资源丰富，但相关的植物雌激素的系统研究很少，所以在其中筛选具雌激素作用的药物，并进一步筛选有效成分意义重大，不仅在理论上，而且在临床上也是实际可行的。 由于每种中药的成分比较复杂，并且每种中药植物雌激素活性不同，我们根据中医对更年期综合征的辨证论治的原则，结合文献中对某些含有植物雌激素中药的论述，选出治疗更年期综合征的常用中药，在此基础上做进一步精简，筛选出雌激素活性比较强的中药，减少药物服用量。同时可以根据中医的组方原则，使中药组合变成最佳药物组合，发挥中药的最大作用。本课题还可以了解植物雌激素和选择性雌激素受体调节剂的作用路径及其组织特异性的发生机制，最终为提高雌激素类药物的选择性、优化以临床为基础的药物设计提供一条较为系统的思路。 本课题选取了十种治疗更年期综合征的常用中药(淫羊藿、菟丝子、女贞子、补骨脂、枸杞子、肉苁蓉、甘草、川牛膝、丹参、红花)，这些中药主要分为补肾阴药、补肾阳药、活血化瘀药三大类。在课题中主要从四个方面来研究中药中的植物雌激素。 第一部分：利用小鼠子宫增重法，观察十种中药的雌激素和拮抗雌激素的作用。更多还原

【Abstract】 Menopausal syndrome is owing to the decay of the ovaries fuctions, the estrogen level obviously decends, which causes the functional disorders of blood vessel , nerve and endocrine system, and which induces the functional uterine bleeding, hectic fever, diaphoresis, the atrophy of cunnus and vagina, osteoporosis and neurovegetative syndromes. With the aging of population structure in china, the age of onset shifts to an earlier time and the disease incidence is ascendant, which severely influence the health and quality of life during perimenopausal period and postmenopause occupying one third lifetime.Menopausal syndrome gives a direct impact on the proper functioning and living due to the high incidence , for the moment the dominating therapy is hormone replacement therapy(HRT). Estrogen is a steroid hormone with extensive contribution, which plays an important roles not only in maintaining the reproductive function and the secondary sex characters of the female animals but also in so-classical target tissues, such as the gential tract, mammary gland, bone, cardiovascular system. ERT can lessen the menopausal syndrome, prevent and cure osteoporosis. However, the long-term ERT could increase the onset risk of endometrial cancer . The HRT of the association between progestogen and estrogen grows downwards the risk , but the onset risk of breast cancer, cardiovascular and cerebrovascular disease increase. Although the estrogen gets pretty good curative effect in ameliorating the menopausal syndrome, the clinical sideeffect perplex the women.Phytoestrogens are naturally occurring plant chemicals that can produce an estrogen-like effect in the body, which are capable of binding estrogen receptors and have two-phase regulations. They suppress significantly growth of tumors dependent on estrogens, and also reduce menopausal symptoms. As a natural alternative to HRT , the phytoestrogen gains more and more attention. The source of Chinese medical materials in China is rich, but the study on phytoestrogen is rare. So to screen phytoestrogen from Chinese herbs is practicable and feasible way.The ingredients of each traditional Chinese medicine are complicated and the phytoestrogen activities are different, so we can select Chinese medical materials which are frequently used in clinic according to the theory of traditional Chinese medicine and some phytoestrogen description in the documents,更多还原