Wang Yueru, Wang Xin, Guo Yingying, Bian Yunfei, Bai Rui, Liang Bin, Xiao Chuanshi
Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Shanxi Key Laboratory of Cardiovascular Medicine and Clinical Pharmacology, Taiyuan, Shanxi 030001, P.R. China.
Exp Ther Med. 2017 Jun;13(6):2757-2762. doi: 10.3892/etm.2017.4321. Epub 2017 Apr 10.
The objective of the present study was to investigate the effect of adiponectin (APN) on macrophage reverse cholesterol transport (RCT) in adiponectin-/- knockout mice (APN-/-mice) and its possible anti-atherosclerotic mechanism. A total of 30 male APN-/-mice were randomly divided into the control group and four intervention groups. The intervention groups were treated with intraperitoneal injections of APN, at doses of 50, 150, 200 and 250 µg/(kg/day), respectively, for 4 weeks. The control group received normal saline. After 4 weeks, serum lipid levels were measured, the degree of severity of atherosclerotic lesions was observed by light microscopy, the H-TC (APN-/-mice treated with intraperitoneal injections of H-TC-labeled macrophages) radioactivity in serum, liver, and feces, and the expression of ABCA1 mRNA and protein in liver were determined. Compared with the control group, serum triglycerides, total cholesterol, and low-density lipoproteins levels in the intervention groups were significantly decreased, while high-density lipoprotein was increased. The severity of aortic atherosclerotic lesions in the intervention groups was milder than in the control group, which had obvious aortic atherosclerotic lesions, large lipid deposition on vessel walls, and the formation of atheromatous plaques. In the intervention groups, serum H-TC content was significantly decreased (P<0.05), but the H-TC content in liver and feces was significantly increased (P<0.05). The levels of ABCA1 mRNA in liver of the intervention groups were significantly increased in a dose-dependent manner. In conclusion, APN can promote RCT and intracellular cholesterol efflux by upregulating the expression of ABCA1, to delay the occurrence and development of atherosclerosis.
本研究的目的是探讨脂联素(APN)对脂联素基因敲除小鼠(APN-/-小鼠)巨噬细胞逆向胆固醇转运(RCT)的影响及其可能的抗动脉粥样硬化机制。将30只雄性APN-/-小鼠随机分为对照组和4个干预组。干预组分别腹腔注射剂量为50、150、200和250 μg/(kg/天)的APN,持续4周。对照组给予生理盐水。4周后,测定血脂水平,通过光学显微镜观察动脉粥样硬化病变的严重程度,测定血清、肝脏和粪便中H-TC(腹腔注射H-TC标记巨噬细胞的APN-/-小鼠)放射性,以及肝脏中ABCA1 mRNA和蛋白的表达。与对照组相比,干预组血清甘油三酯、总胆固醇和低密度脂蛋白水平显著降低,而高密度脂蛋白升高。干预组主动脉粥样硬化病变的严重程度比对照组轻,对照组有明显的主动脉粥样硬化病变,血管壁上有大量脂质沉积,并形成动脉粥样斑块。干预组血清H-TC含量显著降低(P<0.05),但肝脏和粪便中H-TC含量显著升高(P<0.05)。干预组肝脏中ABCA1 mRNA水平呈剂量依赖性显著升高。综上所述,APN可通过上调ABCA1的表达促进RCT和细胞内胆固醇外流,从而延缓动脉粥样硬化的发生和发展。