炎症上调SREBP-1致C57BL/6J小鼠肝脏脂质积聚

Inflammation enhances lipid accumulation via up-regulating SREBP1 in liver of C57BL/6J mice

摘要:

目的：研究炎症是否通过影响核转录因子固醇调节元件结合蛋白1(SREBP1)而致C57BL/6J小鼠肝脏脂质的异常聚集。方法：将8周龄C57BL/6J雄性小鼠随机分为对照组(n=6)和炎症组(n=6)组,两组均喂以高脂饮食,炎症组小鼠皮下注射酪蛋白建立慢性炎症模型,对照组注射相应量磷酸盐缓冲液,18周后处死,测定血清中炎症介质水平及肝脏中的脂质水平,油红O染色观察肝脏脂质沉积情况,实时定量PCR和Western blotting检测肝脏炎症因子TNF-α、MCP1及脂肪酸合成相关基因SREBP1、ACCα、FAS的基因和蛋白水平。结果：与对照组相比,炎症组血清中的炎症因子IL-6和SAA水平以及肝脏中炎症因子MCP1 和 TNF-α的mRNA和蛋白水平均显著上升(P<0.05)。炎症状态下,肝脏甘油三酯和游离脂肪酸含量显著高于对照组(分别为0.21?0.07 vs 0.40?0.14mg/mg,P<0.05；3.80?0.58 vs 5.38?1.38nmol/mg,P<0.05)。油红O结果显示,炎症使脂质积聚更显著。SREBP1及其下游与脂肪酸和甘油三酯合成相关的基因ACCα,FAS的mRNA和蛋白水平在炎症组均显著上升(P<0.05)。结论：炎症可能通过上调SREBP1,加重脂质在肝脏的聚集。

Abstract:

objective: To investigate whether inflammation enhances lipid accumulation via SREBP1 in liver of C57BL/6J mice. Methods: 12 male mice were subcutaneously injected with 0.5ml 10% casein or PBS. The mice were fed a high fat diet for 18 weeks. TG and FFA in liver and serum amyloid A (SAA) and IL-6 in serum were assayed. The lipid accumulation in liver was evaluated by Oil Red O staining. The mRNA and protein expression of TNF-α, MCP1, SREBP1, ACCα, FAS were analyzed by Real Time PCR and Western blotting. Results: Casein injection elevated serum levels of IL-6 and SAA in mice. In the liver of casein-injected mice, mRNA and protein expression of TNF-α, MCP-1 were significantly increased compared with control mice, suggesting that inflammatory stress was successfully induced in C57BL/6J mice. The inflammation up-regulated mRNA and protein expression of sterol regulatory element binding protein 1, fatty acid synthase, and acetyl CoA carboxylase alpha in liver of C57BL/6J mice. Conclusions: Inflammation may exacerbate lipid accumulation via up-regulating SREBP1 expression in liver of C57BL/6J mice.