Irie H, Koshiba H, Koyama M, Asakura E, Shibata H, Kimura K, Naito K, Yamauchi T, Yada K, Hanamura T, Hanada S, Nakamura N
Pharmaceutical Research Division, Welfide Corporation, Shodai-Ohtani, Hirakata, Osaka 573-1153, Japan.
J Biochem. 2001 May;129(5):717-24. doi: 10.1093/oxfordjournals.jbchem.a002911.
Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.
利用喂食高胆固醇饮食的兔子研究了人巨噬细胞集落刺激因子的抗动脉粥样硬化作用。喂食含2%胆固醇饮食59天的兔子出现了高脂血症和动脉粥样硬化性主动脉斑块。然后在接下来的12周内，给它们每天注射80微克/千克的巨噬细胞集落刺激因子或作为对照的人血清白蛋白。与对照组相比，接受巨噬细胞集落刺激因子治疗的兔子胸主动脉和腹主动脉内表面的斑块明显减少，主动脉弓以及胸主动脉和腹主动脉内膜增厚的截面积减半。巨噬细胞集落刺激因子还降低了动脉粥样硬化病变的胆固醇含量。血清生化分析显示，巨噬细胞集落刺激因子显著提高了高密度脂蛋白胆固醇水平，而不影响其他脂质参数，如低密度脂蛋白水平。巨噬细胞集落刺激因子的作用在药物注射的第四周之前都很明显，此时血清中明显诱导出了抗人巨噬细胞集落刺激因子抗体。这些结果表明，外源性给予巨噬细胞集落刺激因子可通过激活体内脂质代谢来抑制高胆固醇饮食诱导的动脉粥样硬化病变。
