Grainger D J, Witchell C M, Metcalfe J C
Department of Biochemistry, University of Cambridge, UK.
Nat Med. 1995 Oct;1(10):1067-73. doi: 10.1038/nm1095-1067.
When C57B16 male mice are fed a high-fat diet, they develop significant fatty streak lesions in the aorta. Addition of tamoxifen (TMX) to a high-fat diet, equivalent to a dose of approximately 1 mg TMX per kg body weight per day, suppressed the diet-induced increase in the area of lipid staining in the aortic sinus of the mice by 88% and in the average number of lesions by 86%. The TMX-treated mice had 11% +/- 5% less total plasma cholesterol, with most of the reduction in the high density lipoprotein fraction, whereas plasma triglycerides were significantly elevated, and circulating concentrations of 17 beta-estradiol and testosterone were unaffected. Both circulating and aortic concentrations of active and latent transforming growth factor-beta (TGF-beta) were substantially elevated by TMX. The inhibition of lesion formation may be due, at least in part, to cardiovascular protection by TGF-beta.
当给C57B16雄性小鼠喂食高脂饮食时，它们的主动脉会出现明显的脂肪条纹病变。在高脂饮食中添加他莫昔芬（TMX），相当于每天每千克体重约1毫克TMX的剂量，可使饮食诱导的小鼠主动脉窦脂质染色面积增加减少88%，病变平均数量减少86%。经TMX处理的小鼠总血浆胆固醇降低了11%±5%，大部分降低发生在高密度脂蛋白部分，而血浆甘油三酯显著升高，且循环中的17β-雌二醇和睾酮浓度未受影响。TMX使循环和主动脉中活性和潜伏性转化生长因子-β（TGF-β）的浓度大幅升高。病变形成的抑制至少部分可能归因于TGF-β的心血管保护作用。
