引用本文:田 琳,谢友红,刘 宏.炎症促进CCl4诱导的小鼠肝细胞脂质集聚与SREBP-1-HMGCR通路活化有关[J].重庆医科大学学报,2014,38(7):969~973
炎症促进CCl4诱导的小鼠肝细胞脂质集聚与SREBP-1-HMGCR通路活化有关
Inflammatory stress aggravating CCl4-induced hepatic lipid accumulation in the mice via SREBP-1-HMGCR pathway
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中文关键词:  炎症  四氯化碳  固醇调节元件结合蛋白1  3-羟基-3-甲基戊二酰辅酶A还原酶
英文关键词:inflammation  carbon tetrachloride  sterol regulatory element binding proteins-1  3-Hydroxy-3-methylglutaryl-coen-zyme A reductase
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田 琳,谢友红,刘 宏 重庆医科大学附属第一医院消化内科重庆 400016 
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中文摘要:
      目的:探讨炎症促进四氯化碳(carbon tetrachloride,CCl4)所致的小鼠单纯性脂肪变性进一步脂肪集聚的分子机制。方法:12只6~8周龄C57BL/6J雄性小鼠随机分为对照组(n=6)和炎症组(n=6)。2组均CCl4皮下注射2周后,再分别给予皮下注射生理盐水或酪蛋白16周,18周后处死小鼠,收集血清及肝组织标本,称量小鼠体质量及肝质量计算肝指数评估肝脏受损情况,ELISA法检测血清炎症因子白介素-6(interleukin-6,IL-6),使用化学酶促比色法检测小鼠肝组织的脂质水平,油红O染色观察小鼠肝组织的脂质集聚情况,real-time PCR检测小鼠固醇调节元件结合蛋白1(sterol regulatory element binding proteins-1,SREBP-1)和3-羟基-3-甲基戊二酰辅酶A还原酶(3-Hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)的基因表达水平,Western blot检测SREBP-1和HMGCR的蛋白表达水平。结果:炎症组IL-6的表达比对照组明显升高(t=8.434,P=0.000)。与对照组相比,炎症组的SREBP-1 和HMGCR基因的表达明显上调(t=10.612,P=0.000;t=12.749,P=0.000),Western blot显示SREBP-1和 HMGCR的蛋白表达趋势与基因一致。肝脏脂质检测显示炎症组比对照组的肝脏脂质明显升高(t=6.148,P=0.000;t=7.288,P=0.000)。肝指数提示与对照组相比,炎症组的肝指数明显升高(t=8.452,P=0.000),油红O染色显示炎症组的脂质集聚明显高于对照组。结论:炎症因子可能通过促进SREBP-1-HMGCR表达使CCl4所致的小鼠脂肪变性肝细胞胆固醇内源性合成增加,加重肝脏脂质的异常集聚。
英文摘要:
      Objective:To investigate whether inflammatory stress aggravates hepatosteatosis induced by carbon tetrachloride(CCl4) and the molecular mechanism. Methods:Male C57BL/6J mice of 6-8 weeks were randomly divided into control group(n=6) and inflam-mation group(n=6). Inflammation was induced via subcutaneous casein injection of casein for 16 weeks after the treatment of CCl4 for 2 weeks. After 18 weeks,the liver indicator was measured to study the damage to the liver. Level of serum inflammatory factor inter-leukin-6(IL-6) was determined by ELISA. Oil red O staining was used to evaluate lipid accumulation in the liver. Lipid levels of liver tissues were measured by chemical enzymatic assay. mRNA expression of SREBP-1 and 3-hydroxy-3-methylglutaryl coenzyme A re-ductase(HMGCR) was measured by real-time PCR and the protein expression of SREBP-1 and HMGCR was analyzed by Western blot. Results:Expression of IL-6 was higher in inflammation group than in control group(t=8.434,P=0.000). Expression of HMGCR and SREBP-1 mRNA was significantly increased in inflammation group than in control group(t=10.612,P=0.000;t=12.749,P=0.000). Expressions of SREBP-1 and HMGCR protein were consistent with the mRNA levels based on Western blot. Hepatic lipid levels were significantly higher in inflammation group than in control group(t=6.148,P=0.000;t=7.288,P=0.000). Liver indicator of mice were significantly higher in inflammation group than in control group(t=8.452,P=0.000). Increased lipid accumulation demonstrated by Oil red O staining was observed in inflammation group. Conclusion:Inflammatory stress probably promotes cholesterol synthesis in fatty liver induced by CCl4 via SREBP-1-HMGCR pathway,which may contribute to the abnormal lipid accumulation in the liver.
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