摘要目的 探讨清道夫受体A在脂肪乳剂代谢中的作用及其对长链(LCT)脂肪乳剂和鱼油(FO)脂肪乳剂分解代谢作用的差异。方法 采用随机数字表将24只10~12周龄清洁级C57BL/6J雌性小鼠随机分为4组,每组6只,其中两组经股静脉注射硫酸葡聚糖(1 mg/只),2 min后分别经股静脉注射[1α,2α(n)-3H]胆固醇油烯醚[(3H)CEt]标记的LET和FO脂肪乳剂(0.4 mg甘油三酯/只);另外两组为对照组,先经股静脉注射生理盐水,2 min后分别经股静脉注射与实验组等量的(3H)CEt标记的LCT和FO脂肪乳剂。分别于脂肪乳剂注射后0.5、2、5、1O、15和25 min采集眼眶静脉血测定放射性,计算脂肪乳剂的血液清除率。同样的流程,给小鼠静脉注射非标记脂肪乳剂LCT和FO,于非标记脂肪乳剂注射后2 min处死小鼠,取肝组织,电子显微镜下观察肝组织对脂肪乳剂的摄取情况。同时观察硫酸葡聚糖对体外培养THP1细胞摄取脂肪乳剂的影响。结果 预注射硫酸葡聚糖C57BL/6J小鼠的血液LCT和FO脂肪乳剂清除率分别降低了72.38%和47.38% (P =0.020)。电子显微镜下观察发现,预注射硫酸葡聚糖的小鼠,注射LET和FO脂肪乳剂后,肝窦内皮细胞和枯否细胞中脂滴数量呈等量减少;注射LCT脂肪乳剂2 min后,肝细胞中未出现脂滴,而注射FO脂肪乳剂2 min后,肝细胞中可见脂滴,但脂滴数量较未注射硫酸葡聚糖的小鼠少。体外细胞培养显示:硫酸葡聚糖预处理THP-1细胞对LCT和FO脂肪乳剂的摄取分别减少了30.74%和41.60%(p值分别为0.003和0.008);但硫酸葡聚糖对THP-1细胞摄取两种脂肪乳剂的影响的差异无统计学意义(P =0.080)。结论 清道夫受体A在脂肪乳剂的分解代谢过程中发挥一定作用,其对FO脂肪乳剂分解代谢的影响可能小于LCT脂肪乳剂。
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abstractsObjective To investigate the effects of scavenger receptor A on the catabolism of lipid emulsions and further to see if it differently affects long-chain triglyceride (LCT) and fish oil (FO) emulsions. Methods A total of 24 C57BL/6J female mice, 10 to 12 weeks old, were randomly divided into 4 groups with 6 mice in each group. Two groups of mice were intravenously injected with dextran sulfate ( DexSO4 ) ( 1 mg/mouse) followed by intravenous injection of [1α, 2α(n)-3H] cholesteryl oleoyl ether [(3H)CEt] labelled LCT or FO emulsions (0.4mg triglycerde/mouse) at 2 minutes respectively, and other two groups were injected by saline as controls before injection of (3H)CEt labelled LCT and FO emulsions. Then, blood was drawn at fixed intervals to measure the radioactivities and the emulsion's fractional catabolic rates (FCR) were calculated. With the same procedures above mentioned, non-radiolabelled LCT and FO emulsions were intravenously injected to mice to determine liver uptake of lipid emulsions under electromicroscopy. Finally, THP1 cell line was used to examine the effects of DexSO4 on cell uptake of LCT and FO emulsions in vitro. Results Pre-injection of DexSO4 to mice decreased the FCR of both LCT and FO emulsions at 72.38% and 47.38% respectively, as compared to controls ( P =0.020 ). Electromicroscopy showed that pre-injection of DexS04 decreased the uptakes of LCT and FO emulsions by Kupffer cells and sinusoidal endothelial cells similarly. In hepatocytes, no lipid droplets existed in mice with LCT emulsion injection, whereas some lipid droplets were still shown in mice with FO emulsions but with less quantities compared to control mice.In vitro, addition of DexSO4 to medium decreased THP1 cell uptakes of LCT and FO emulsions ( P =0.003 and 0.008) by 30.74% and 41.60% respectively. However, no differences were found in the effects of DexS04 on cell uptakes between LCT and FO emulsions ( P =0.080). Conclusion Scavenger receptor A plays important roles in catabolism of lipid emulsions to some extent, and it's effects on FO emulsions may be less than LCT emulsions.
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