17β雌二醇和α玉米赤霉醇影响大鼠血液凝固和纤维蛋白溶解功能
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Effects of 17β-Estradiol and Phytoestrogen α-Zearalanolon Coagulation and Fibrinolysis in Rats
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    摘要:

    为探讨17β雌二醇及植物雌激素α玉米赤霉醇对去势大鼠凝血及纤溶功能的影响,并对二者的作用进行比较分析。选用36只健康成年雌性Wistar大鼠,随机分为4组(每组均为9只) :假手术对照组;去卵巢组;去卵巢+补充17β雌二醇组,去卵巢14天后肌注17β雌二醇(1mg kg ,3天注射一次,共35天) ;去卵巢+补充α玉米赤霉醇组,去卵巢14天后肌注α玉米赤霉醇(1mg kg ,3天注射一次,共35天)。实验结束后大鼠经颈总动脉采血,分离血浆。用凝固法测定血浆凝血酶原时间及活化部分凝血活酶时间。用全自动生物化学分析仪测定血浆纤维蛋白原水平。用酶联免疫吸附法测定血浆组织因子水平。组织型纤溶酶原激活剂及纤溶酶原激活剂抑制物活性测定均采用发色底物法。结果发现,去卵巢组大鼠与对照组相比,凝血酶原时间明显缩短,而纤维蛋白原,组织因子等均明显升高,组织型纤溶酶原激活剂活性明显降低,而纤溶酶原激活剂抑制物活性明显升高;补充17β雌二醇组或α玉米赤霉醇后,除纤溶酶原激活剂抑制物活性下降不明显外,大鼠的其他上述指标均与对照组接近,而与单纯去卵巢组有显著性差异。各组间活化部分凝血活酶时间的变化尚无统计学差异。以上结果表明,大鼠去卵巢后,内源性雌激素水平下降,导致凝血活性增高,纤溶活性下降,血液处于高凝状态,易于发生血栓性疾病。补充外源性17β雌二醇或α玉米赤霉醇后,凝血活性均明显降低,接近于假手术对照组,同时纤溶活性有所回升,重新建立起凝血—纤溶的动态平衡,这可能是雌激素替代治疗降低血栓性疾病的发生,对心血管系统产生保护效应的重要机制之一。本实验中,α玉米赤霉醇对凝血和纤溶功能的影响同17β雌二醇相似,但刺激子宫的副作用明显小于17β雌二醇,是一种有一定应用前景的雌激素替代药物,其具体的作用机制值得进一步深入研究。

    Abstract:

    Aim To investigate the effects of 17β-estradiol andα-zearalanol on coagulation and fibrinolysis in ovariectomized rats. Methods Female Wistar rats were divided into four groups (n=9 each group): sham operated (sham), ovariectomized (OVX), ovariectomized and treated with 17β-estradiol (OVX+E2), ovariectomized and treated withα-zearalanol(OVX+ZAL). After administration of 17β-estradiol or α-zearalanol for 5 weeks, rats were killed and plasma was collected. The following parameters were tested: the prothrombin time (PT) and the activated partial thromboplastin time (APTT), the level of fibrinogen (FG) and tissue factor (TF), the activity of tissue plasminogen activator (t-PA)as well as plasminogen activator inhibitor type 1 (PAI-1). Results Ovariectomy markedly decreased PT and the activity of t-PA, as well as increased the level of FG, TF and the activity of PAI-1 in comparision with sham operated group (p<0.05 or p<0.01). These changes were reversed by 17β-estradiol or α-zearalanol replacement. Except for PAI-1, these parameters about coagulation and fibrinolysis were similar among sham, OVX+E2 and OVX+ZAL. There was no significant difference on the value of APTT among the four groups (P>0.05). Conclusion After ovariectomy, as the endogenous estrogen decreases, the blood is hypercoagulative than ever; treating with 17β-estradiol or α-zearalanol can reverse this change. Both 17β-estradiol and α-zearalanol have protective effects on cardiovascular system. Prior study has shown that compared with 17β-estradiol, α-zearalanol has less side effects so more attention should be paid to this natural phytoestrogen.

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王雯,朱广瑾,祖淑玉.17β雌二醇和α玉米赤霉醇影响大鼠血液凝固和纤维蛋白溶解功能[J].中国动脉硬化杂志,2004,12(2):139~142.

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  • 收稿日期:2003-05-12
  • 最后修改日期:2004-01-05
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