益气止血宁治疗功能失调性子宫出血止血机制的实验研究
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摘要
益气止血宁是导师马宝璋教授在长期临床实践中总结提炼出来的治疗妇科出血性疾病,尤其是功能失调性子宫出血属于脾肾不足型的有效方剂。为了能够探讨其对功血止血的作用机制,为临床提供有力的实验证据,本文突破常规选择动物模型的思路,以性腺轴及靶器官结构功能调节模型、凝血机能调节模型、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有益的实验研究,结果如下:
     1.益气止血宁的水溶液及药物血清均能加强离体子宫的收缩功能,加强了子宫平滑肌张力,有利于子宫止血。
     2.益气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凝血止血作用。
     3.益气止血宁能加强子宫组织的止血调节机制:原位杂交结果表明本方能促进子宫组织ERmRNA和PRmRNA的表达;免疫组化方法证实益气止血宁低剂量能提高子宫组织ET表达。
     4.益气止血宁能双向调节性腺轴功能:(1)低剂量的益气止血宁能提高卵巢系数,高剂量则略减低该值,两剂量差异显著。(2)益气止血宁低剂量可提高未成熟大鼠血清FSH、LH、E_2、P值;高剂量则有不显著的下调趋势,但与低剂量组之间差异显著。(3)低剂量的益气止血宁可提高未成熟大鼠下丘脑ERmRNA的表达,高剂量未能提高其表达,与低剂量差异显著。
     结论:益气止血宁对功血具有多层次、多途径、多靶点的止血和调节作用。
Yiqizhixuening granule is effective recipe to cure gynecologic hemorrhagic disease especially dysfunctional uterine bleeding belonging to the spleen-kidney insufficiency type which professor Ma Bao Zhang summurizes from long-term clinical practice. To probe hemostatic mechanism of Yiqizhixuening and to provides powerful experimental evidence for clinic, we break routine thinking of animal model for experiment and select several experimental animal models and design "models association" to study using technology of in situ hybridization, immunohistochemist^ serum pharmcology^ radioimmunoassay. Result:
    1.Both of solution and pharmacological serum of Yiqizhixuening can increase contraction function and smooth muscle's tension of uterus isolated from the whole body.
    2.Yiqizhixuening can decrease mouse bleeding time ,coagulation time and also decrease prothrombin timeN activated partial thromboplastin time of rat.It shows that Yiqizhixuening has multiple-channels coagulation function.
    3.Yiqizhixuening can regulating mechanism of uterus local hemostasis: Yiqizhixuening can promote the mRNA expression of estrogen receptor and progestogen receptor in uterine tissue by in situ hybridization method; Yiqizhixuening of low-dose can increase endothelin expression in uterus tissue by immunohistochemistry method.
    4. Yiqizhixuening has two-way regulation to the function of HPOA: (l)The low-dose of Yiqizhixuening can improve ovarian coefficient, but the high-dose of Yiqizhixuening decrease it slightly. It shows that two gropes have notable discrepancy.(2)The law-dose of Yiqizhixuening can increase FSH> LH> EZ> P in serum of immature rat, but the high-dose of Yiqizhixuening has down-regulating trend. It shows two groups have notable discrepancy. (3 )The law-dose of Yiqizhixuening can increase expression of ERmRNA in immature rat's hypothalamus, but the
    
    
    high-dose of Yiqizhixuening can not. Two groups have notable discrepancy.
    Conclusion: Yiqizhixuening has multiple-levels, multiple-channels multiple-targets hemostatic and regulating function to treat dysfunctional uterine bleeding.
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