CAJ | 학술논문

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。
목적 탐토청도부수체A재지방유제대사중적작용급기대장련(LCT)지방유제화어유(FO)지방유제분해대사작용적차이。방법 채용수궤수자표장24지10～12주령청길급C57BL/6J자성소서수궤분위4조，매조6지，기중량조경고정맥주사류산포취당（1 mg/지），2 min후분별경고정맥주사[1α，2α(n)-3H]담고순유희미[(3H)CEt]표기적LET화FO지방유제(0.4 mg감유삼지/지)；령외량조위대조조，선경고정맥주사생리염수，2 min후분별경고정맥주사여실험조등량적(3H)CEt표기적LCT화FO지방유제。분별우지방유제주사후0.5、2、5、1O、15화25 min채집안광정맥혈측정방사성，계산지방유제적혈액청제솔。동양적류정，급소서정맥주사비표기지방유제LCT화FO，우비표기지방유제주사후2 min처사소서，취간조직，전자현미경하관찰간조직대지방유제적섭취정황。동시관찰류산포취당대체외배양THP1세포섭취지방유제적영향。결과 예주사류산포취당C57BL/6J소서적혈액LCT화FO지방유제청제솔분별강저료72.38％화47.38％ (P =0.020)。전자현미경하관찰발현，예주사류산포취당적소서，주사LET화FO지방유제후，간두내피세포화고부세포중지적수량정등량감소；주사LCT지방유제2 min후，간세포중미출현지적，이주사FO지방유제2 min후，간세포중가견지적，단지적수량교미주사류산포취당적소서소。체외세포배양현시：류산포취당예처리THP-1세포대LCT화FO지방유제적섭취분별감소료30.74％화41.60％（p치분별위0.003화0.008）；단류산포취당대THP-1세포섭취량충지방유제적영향적차이무통계학의의(P =0.080)。결론 청도부수체A재지방유제적분해대사과정중발휘일정작용，기대FO지방유제분해대사적영향가능소우LCT지방유제。
Objective 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.