[1]陈小乐,龚建平,徐发良.脂多糖预处理导致的糖原合成酶激酶-3抑制对肝糖原的影响和机制[J].南方医科大学学报,2014,(02):201.
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脂多糖预处理导致的糖原合成酶激酶-3抑制对肝糖原的影响和机制()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2014年02期
页码:
201
栏目:
出版日期:
2014-02-15

文章信息/Info

Title:
Effect of endotoxin pretreatment-induced glycogen synthase kinase-3 inhibition on
glycogen metabolism in rat liver and the mechanism
作者:
陈小乐龚建平徐发良
关键词:
糖原合成酶激酶-3糖原代谢脂多糖肝损伤氯化锂器官保护
Keywords:
glycogen synthase kinase-3 glycogen metabolism endotoxin lipopolysaccharide liver injury lithium chlorideorgan protection
摘要:
目的探讨脂多糖预处理时糖原合成酶激酶3(glycogen synthase kinase-3, GSK-3)功能活性的变化及其对肝组织糖原代
谢的影响和机制。方法雄性SD大鼠随机分为正常对照、脂多糖预处理和GSK-3抑制剂氯化锂预处理组,分别进行相应处理后
再接受大剂量脂多糖(10 mg/kg)攻击以建立脂多糖诱导的急性肝损伤模型;采用PAS染色法观察肝组织糖原聚集,用试剂盒法
定量检测肝组织糖原含量,以Western Blot法半定量分析GSK-3的蛋白表达和抑制性磷酸化水平,采用考马斯亮兰比色法测定
肝组织钙依赖蛋白酶的活性。结果尽管大剂量脂多糖攻击后各组动物肝组织糖原含量组间比较均无显著差异(P>0.05),但均
较攻击前有显著降低(P<0.05),且脂多糖和氯化锂预处理均可导致肝组织糖原含量增加(P<0.05);尽管诱导脂多糖预处理并未
改变GSK-3的蛋白表达水平(P>0.05),但导致GSK-3β抑制性磷酸化(P<0.05)和GSK-3α不完全裂解;大剂量脂多糖攻击后肝组
织钙依赖蛋白酶活性较前显著升高(P<0.05),但组间比较无显著差异(P>0.05)。结论脂多糖预处理导致GSK-3β抑制性磷酸
化和GSK-3α不完全裂解,促进肝组织糖原合成和聚集,但不影响钙依赖蛋白酶活性,有利于增加肝组织糖原储备并可能在遭受
大剂量脂多糖攻击时提供能量需求。
Abstract:
Objective To investigate the changes in the functional activity of glycogen synthase kinase-3 (GSK-3) in the hepatic
tissue after endotoxin (lipopolysaccharide, LPS) tolerance and explore the effects of LPS-induced GSK-3 inhibition on glycogen
metabolism in the liver. Methods Male SD rats were randomly divided into normal control, endotoxin pretreatment and
GSK-3 inhibitor (lithium chloride) groups with corresponding pretreatments prior to a large dose of LPS challenge (10 mg/kg)
to induce liver injury. Glycogen deposition and content in the hepatic tissue was detected using periodic acid-Schiff (PAS)
staining and a glycogen quantification kit, respectively. Western blotting was performed for semi-quantitative analysis of
protein level and inhibitory phosphorylation of GSK-3, and a Coomassie brilliant blue G-250-based colorimetric assay was
used to detect calpain activity in the liver. Results Glycogen content in the liver decreased significantly after LPS challenge in
all the 3 groups (P<0.05) but showed no significant difference among the groups (P>0.05). Both LPS and lithium chloride
pretreatments caused a significant increase of liver glycogen content (P<0.05). LPS pretreatment induced inhibitory
phosphorylation of GSK-3β (P<0.05) and partial cleavage of GSK-3α but did not affect the expression of GSK-3 protein (P>
0.05). Large-dose LPS challenge significantly increased the activity of calpain in the liver tissue (P<0.05) to a comparable level
in the 3 groups (P>0.05). Conclusion Endotoxin pretreatment induces inhibitory phosphorylation of GSK-3β and partial
cleavage of GSK-3α and promotes the deposition of liver glycogen but does not affect the activity of calpain, which may
contribute to an increased glycogen reserve for energy supply in the event of large-dose LPS challenge.
更新日期/Last Update: 1900-01-01