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李秀兰,柳青,雷寒,刘宏,陈压西,阮雄中.炎症对SRA/CD36双基因敲除小鼠肝LDL受体表达的影响[J].陆军军医大学学报(原第三军医大学学报),2009,31(15):1436-1439.
LI Xiu-lan,LIU Qing,LEI Han,LIU Hong,CHEN Ya-xi,RUAN Xiong-zhong.Effects of inflammatory stress on LDL receptor expression in the liver of SRA/CD36 double knockout mice and its potential mechanisms[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(15):1436-1439.
李秀兰,柳青,雷寒,刘宏,陈压西,阮雄中.炎症对SRA/CD36双基因敲除小鼠肝LDL受体表达的影响[J].陆军军医大学学报(原第三军医大学学报),2009,31(15):1436-1439. DOI:
LI Xiu-lan,LIU Qing,LEI Han,LIU Hong,CHEN Ya-xi,RUAN Xiong-zhong.Effects of inflammatory stress on LDL receptor expression in the liver of SRA/CD36 double knockout mice and its potential mechanisms[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(15):1436-1439. DOI:
目的 探讨炎症对清道夫受体A(scavenger receptor A
SRA)和CD36双基因敲除(SRA
-/-
/CD36
-/-
)小鼠肝脏LDL受体表达的影响及其潜在机制。 方法 将1~3月龄,体质量为18~23 g的SRA
-/-
/CD36
-/-
雄性小鼠随机分为对照组(n=7),炎症组(n=6),2组均喂以高脂饮食,炎症组小鼠采取皮下注射酪蛋白方法诱导产生慢性炎症模型,14周后应用实时荧光定量RT-PCR技术和免疫组化方法检测肝脏LDL受体基因及调控其转录的SREBP2、SCAP基因表达水平,并观察肝脏形态学及血生化指标的变化。 结果 与正常对照相比,炎症状态时肝脏LDL受体、SREBP2、SCAP mRNA水平显著高于对照组(P0.05),蛋白表达的水平也较对照组明显升高;肝细胞内脂质沉积加重,炎性细胞浸润;血清总胆固醇和低密度脂蛋白胆固醇水平均明显降低(P0.05),高密度脂蛋白胆固醇、甘油三酯降低不明显。 结论 炎症通过促进肝细胞内SREBP2、SCAP的表达,进而增强细胞膜表面LDL受体的表达,最终导致肝细胞内胆固醇沉积。
Objective To investigate the effects of inflammatory stress on low density lipoprotein (LDL) receptor (LDLr) expression in the liver of scavenger receptor A (SRA)/CD36 double knockout mice and its potential mechanisms. Methods Male SRA/CD36 double knockout mice with body weight from 18 grams to 23 grams and age from 1 month to 3 months were randomly divided into control group (n=7) and inflammation group (n=6). All mice were fed with high lipid diet containing 15% fat and 1.25% cholesterol
and 0.5% bile acid. Casein was injected subcutaneously in mice in the inflammation group to induce inflammatory stress. After 14 weeks
both mRNA and protein expressions of LDLr
sterol regulatory element binding protein 2 (SREBP2) and SREBP cleavage-activating protein (SCAP) genes in the liver were examined by real-time fluorescence quantitative reverse transcription polymerase chain reaction and immunohistochemistry staining
respectively. Serum levels of total cholesterol (TC)
triglyceride (TG)
LDL and high-density lipoprotein (HDL) were measured by biochemical techniques. Serum concentration of serum amyloid protein (SAA) was determined by ELISA. Frozen sections of liver were stained with Oil Red O to visualize the lipid accumulation. Results Under inflammatory stress
the expressions of LDLr
SCAP and SREBP2 genes increased significantly as compared with those in the control group (P0.05). Lipid accumulation in the liver also increased. Serum levels of TC and LDL-C
not TG and HDL-C were significantly lower (P0.05). Conclusion Inflammatory stress can up-regulate the expressions of SREBP2
SCAP and LDLr genes in the liver of SRA/CD36 double knockout mice. This may contribute to the lipid accumulation in the liver.
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