Hanke H, Hanke S, Finking G, Muhic-Lohrer A, Mück A O, Schmahl F W, Haasis R, Hombach V
College of Medicine, Department of Internal Medicine, University of Ulm, Germany.
Circulation. 1996 Jul 15;94(2):175-81. doi: 10.1161/01.cir.94.2.175.
The aim of the present study was to compare the effect of estrogen and progesterone on the development of experimental atherosclerosis in female versus male rabbits to assess possible sex-specific differences.
A total of 32 female and 32 male New Zealand White rabbits were ovariectomized or castrated. In addition to a 0.5% cholesterol diet, the rabbits received estradiol alone (1 mg/kg body wt [BW] per week), progesterone alone (25 mg/kg BW per week), or combined estradiol-progesterone in these dosages during 12 weeks. Ovariectomized female and castrated male rabbits served as control groups without hormone treatment. Before excision of the vessels, bromodeoxyuridine labeling was performed to determine the extent of cellular proliferation in the atherosclerotic lesions. The aortic arch was analyzed immunohistologically and morphometrically. An inhibitory effect of estrogen on intimal plaque size was found in female rabbits compared with the ovariectomized control group (0.7 +/- 0.5 versus 3.7 +/- 2.5 mm2, P < .002; proliferating cells, 3.1 +/- 1.8% versus 8.5 +/- 2.6%, P < .002). In combination with progesterone, however, estrogen was not able to reduce intimal plaque size or cellular proliferation. In contrast, estradiol in castrated male rabbits was not associated with an inhibitory effect on cellular proliferation or intimal thickening compared with controls (estrogen treatment, 7.6 +/- 2.1% proliferating cells and 2.8 +/- 1.0 mm2 neointima; control group, 7.2 +/- 2.1% cellular proliferation and 2.9 +/- 1.2 mm2 intimal thickening).
Our data suggest that the atheroprotective effect of estrogen is probably due to a mechanism that is present in female rabbits only.
本研究的目的是比较雌激素和孕激素对雌性与雄性兔实验性动脉粥样硬化发展的影响，以评估可能存在的性别特异性差异。
总共32只雌性和32只雄性新西兰白兔接受了卵巢切除术或去势手术。除了给予0.5%胆固醇饮食外，这些兔子在12周内分别单独接受雌二醇（每周1毫克/千克体重）、单独接受孕酮（每周25毫克/千克体重）或按这些剂量联合接受雌二醇 - 孕酮治疗。卵巢切除的雌性兔和去势的雄性兔作为未接受激素治疗的对照组。在切除血管之前，进行溴脱氧尿苷标记以确定动脉粥样硬化病变中细胞增殖的程度。对主动脉弓进行免疫组织学和形态学分析。与卵巢切除的对照组相比，发现雌激素对雌性兔内膜斑块大小有抑制作用（0.7±0.5对3.7±2.5平方毫米，P<.002；增殖细胞，3.1±1.8%对8.5±2.6%，P<.002）。然而，与孕酮联合使用时，雌激素无法减小内膜斑块大小或细胞增殖。相比之下，与对照组相比，去势雄性兔中的雌二醇对细胞增殖或内膜增厚没有抑制作用（雌激素治疗组，7.6±2.1%增殖细胞和2.8±1.0平方毫米新生内膜；对照组，7.2±2.1%细胞增殖和2.9±1.2平方毫米内膜增厚）。
我们的数据表明，雌激素的抗动脉粥样硬化作用可能仅归因于雌性兔中存在的一种机制。
