Inflammatory stress aggravating CCl4-induced hepatic lipid accumulation in the mice via SREBP-1-HMGCR pathway

Tian Lin; Xie Youhong; Liu Hong

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Inflammatory stress aggravating CCl4-induced hepatic lipid accumulation in the mice via SREBP-1-HMGCR pathway

更新时间：2023-12-18

- Inflammatory stress aggravating CCl4-induced hepatic lipid accumulation in the mice via SREBP-1-HMGCR pathway
- Journal of Chongqing Medical University Vol. 38, Issue 7, Pages: 969-973(2014)
- 作者机构：
  
  重庆医科大学附属第一医院消化内科,重庆,400016
- 作者简介：
- 基金信息：
- DOI：
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- Published：2014，
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Tian Lin, Xie Youhong, Liu Hong. Inflammatory stress aggravating CCl4-induced hepatic lipid accumulation in the mice via SREBP-1-HMGCR pathway. [J]. Journal of Chongqing Medical University 38(7):969-973(2014)
DOI：

Tian Lin, Xie Youhong, Liu Hong. Inflammatory stress aggravating CCl4-induced hepatic lipid accumulation in the mice via SREBP-1-HMGCR pathway. [J]. Journal of Chongqing Medical University 38(7):969-973(2014) DOI：

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。

Abstract

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.

关键词

炎症四氯化碳固醇调节元件结合蛋白13-羟基-3-甲基戊二酰辅酶A还原酶

Keywords

inflammationcarbon tetrachloridesterol regulatory element binding proteins-13-Hydroxy-3-methylglutaryl-coen－zyme A reductase

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