Castelo-Branco C, Sanjuán A, Casals Elena, Ascaso C, Colodrón Marta, Vicente J J, Mercader Immaculada, Escaramís G, Blümel J E, Ordi J, Vanrell J A
Menopause Clinic, Department of Gynecology and Obstetrics, Public Health Department, Hospital Clínic Provincial, University of Barcelona, Spain.
J Obstet Gynaecol. 2004 Jan;24(1):47-51. doi: 10.1080/01443610310001620297.
Raloxifene, a selective oestrogen receptor modulator, is effective in the treatment of osteoporosis without stimulating the breast and the endometrium. Although it is associated with a decrease of cardiovascular risk markers the effect of these changes on atherogenesis, is not clear. In this study, we aimed to investigate the effect of raloxifene on aorta atherogenesis. A total of 32 cholesterol-fed New Zealand white rabbits were studied for 4 months. Twenty-four rabbits underwent bilateral ovariectomy; of these eight received raloxifene (group OR), eight received oestradiol valerate (group OE) and eight received placebo after sterilisation (group OP). Finally, another eight were sham-operated (non-ovariectomised) and received placebo with a hypercholesterolaemic diet (group SP). After the diet, total levels of cholesterol increased in group SP from 111.25 +/- 34.8 mg/dl to 1112.25 +/- 364.2, in group OP from 122.62 +/- 27.7 mg/dl to 1367.37 +/- 348.4, in group OE from 65.25 +/- 17.01 to 1710.5 +/- 356.2 and in group OR from 108.88 +/- 15.54 mg/dl to 1407.86 +/- 397.7 (no significant differences). At 4 months, in both treated and untreated rabbits, the cholesterol-rich diet caused atherosclerotic lesions affecting 24.51 +/- 16.1% for group SP, 30.47 +/- 12.2% for group OP, 30.31 +/- 18.07% for group OR and 17.91 +/- 10.19 for group OE (P<0.05) of the aortic surface, respectively. Aortic cholesterol expressed as mg of cholesterol/mg aortic weight was found to decrease in raloxifene-treated rabbits: 3.82 +/- 2.14 mg col/aortic mg versus 8.55 +/- 4.63 (group OP) and 11.97 +/- 11.33 (group SP). P<0.001. Raloxifene reduced aortic cholesterol content but not the atherosclerotic plaque extension in cholesterol-fed ovariectomised rabbits.
雷洛昔芬是一种选择性雌激素受体调节剂，可有效治疗骨质疏松症，且不会刺激乳腺和子宫内膜。尽管它与心血管风险标志物的降低有关，但这些变化对动脉粥样硬化形成的影响尚不清楚。在本研究中，我们旨在研究雷洛昔芬对主动脉粥样硬化形成的影响。总共对32只喂食胆固醇的新西兰白兔进行了4个月的研究。24只兔子接受了双侧卵巢切除术；其中8只接受雷洛昔芬治疗（OR组），8只接受戊酸雌二醇治疗（OE组），8只在绝育后接受安慰剂治疗（OP组）。最后，另外8只进行了假手术（未切除卵巢），并接受含高胆固醇饮食的安慰剂治疗（SP组）。饮食后，SP组的总胆固醇水平从111.25±34.8mg/dl增加到1112.25±364.2mg/dl，OP组从122.62±27.7mg/dl增加到1367.37±348.4mg/dl，OE组从65.25±17.01mg/dl增加到1710.5±356.2mg/dl，OR组从108.88±15.54mg/dl增加到1407.86±397.7mg/dl（无显著差异）。4个月时，在接受治疗和未接受治疗的兔子中，富含胆固醇的饮食均导致了动脉粥样硬化病变，分别影响SP组主动脉表面的24.51±16.1%、OP组的30.47±12.2%、OR组的30.31±18.07%和OE组的17.91±10.19%（P<0.05）。发现雷洛昔芬治疗的兔子主动脉胆固醇以mg胆固醇/mg主动脉重量表示有所降低：3.82±2.14mg胆固醇/主动脉mg，而OP组为8.55±4.63mg胆固醇/主动脉mg，SP组为11.97±11.33mg胆固醇/主动脉mg。P<0.001。雷洛昔芬降低了喂食胆固醇的去卵巢兔子的主动脉胆固醇含量，但没有减少动脉粥样硬化斑块的扩展。
