Koo S I, Lee C C, Norvell J E
Department of Biochemistry, Oral Roberts University School of Medicine, Tulsa, Oklahoma 74171.
Proc Soc Exp Biol Med. 1988 Sep;188(4):410-9. doi: 10.3181/00379727-188-42753.
The lymphatic absorption of cholesterol and plasma clearance of chylomicrons were investigated in Cu-deficient rats (CuD) fed 0.5 mg Cu/kg diet, as compared with Cu-adequate control rats (CuA) fed 7.5 mg/kg diet. Cholesterol absorption was measured by the 14C-radioactivity appearing in the mesenteric lymph at hourly intervals for 8 hr after an intraduodenal dose of [14C]cholesterol. The plasma clearance of chylomicrons was measured at 3, 6, and 10 min after an intravenous dose of chylomicrons labeled in vivo with [3H]retinyl ester. Cumulative [14C]cholesterol absorption and total lymphatic output of cholesterol were significantly decreased in CuD at 4 hr and thereafter, with no change in percentage distribution of free and esterified cholesterol. Over an 8-hr period, 7.3% of the dose was absorbed by CuD and 9.2% by CuA. When [3H]chylomicrons, obtained from a CuD or CuA donor rat, were injected into CuD and CuA recipient rats, the label was cleared faster in CuD during the first 3 min. At 6 and 10 min, however, no significant difference in percentage clearance of the dose was observed between the groups. The half-life (t1/2) of [3H]chylomicrons and the total 3H-radioactivity taken up by the liver during the entire 10-min period did not differ between the groups, regardless of the source of chylomicrons. The activities of both endothelial lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma were markedly lower in CuD. As expressed in micromoles fatty acid released/hr/ml plasma, the activities of LPL in CuD and CuA were 32.6 +/- 1.9 and 45.6 +/- 1.3, respectively. A similar magnitude of difference was also observed in HL activity. The data provide evidence that copper deficiency impairs the intestinal transport of cholesterol and the peripheral lipolysis of chylomicrons. The data, however, strongly suggest that the hepatic uptake of chylomicron remnants via the apo-E-dependent mechanism may not be impaired in Cu deficiency.
研究了饮食中铜含量缺乏的大鼠（CuD，喂食0.5毫克铜/千克饮食）与饮食中铜含量充足的对照大鼠（CuA，喂食7.5毫克/千克饮食）对胆固醇的淋巴吸收和乳糜微粒的血浆清除情况。通过十二指肠内给予[14C]胆固醇后，每隔1小时测量肠系膜淋巴中出现的14C放射性，持续8小时，以此来测定胆固醇的吸收情况。静脉注射体内用[3H]视黄醇酯标记的乳糜微粒后，在3、6和10分钟时测量乳糜微粒的血浆清除情况。在4小时及之后，CuD组中累积的[14C]胆固醇吸收和胆固醇的总淋巴输出量显著降低，游离胆固醇和酯化胆固醇的百分比分布没有变化。在8小时内，CuD组吸收了剂量的7.3%，CuA组吸收了9.2%。当将从CuD或CuA供体大鼠获得的[3H]乳糜微粒注入CuD和CuA受体大鼠时，在最初3分钟内，CuD组中标记物的清除速度更快。然而，在6分钟和10分钟时，两组之间剂量清除百分比没有显著差异。无论乳糜微粒的来源如何，两组之间[3H]乳糜微粒的半衰期（t1/2）以及在整个10分钟期间肝脏摄取的总3H放射性没有差异。CuD组中肝素后血浆中的内皮脂蛋白脂肪酶（LPL）和肝脂肪酶（HL）活性均显著降低。以每小时每毫升血浆中释放的微摩尔脂肪酸表示，CuD组和CuA组中LPL的活性分别为32.6±1.9和45.6±1.3。在HL活性方面也观察到了类似程度的差异。数据表明铜缺乏会损害胆固醇的肠道转运和乳糜微粒的外周脂解作用。然而，数据强烈表明，在铜缺乏的情况下，通过载脂蛋白E依赖性机制对乳糜微粒残粒的肝脏摄取可能不会受到损害。
