非酒精性脂肪肝大鼠脂联素及其受体与肝脏病理改变的关系
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上海市自然科学基金(05ZR14156).


Correlation of serum adiponectin level and adiponectin receptor expression with hepatic pathological changes in rats with non-alcoholic fatty liver diseases
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Supported by Natural Science Foundation of Shanghai(05ZR14156).

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    摘要:

    目的:探讨非酒精性脂肪性肝病(NAFLD)大鼠血清脂联素水平、肝脏脂联素受体(adipoR)mRNA表达与肝组织病理改变的关系。方法:喂养高脂饲料建立NAFLD大鼠模型,分别于第2、4、8、12周处死,ELISA法检测血清脂联素及其他生化指标,测肝指数,RT-PCR法检测肝脏adipoR mRNA表达,肝组织切片苏丹Ⅲ脂肪染色、H-E常规染色和Masson三色纤维染色,显微镜下观察。结果:模型组大鼠第2、4、8、12周血清脂联素水平逐步下降,均低于同期对照组(P均<0.01);血清脂联素水平与肝指数(r=-0.383,P=0.015)、肝脏炎症评分(r=-0.475,P=0.002)、纤维化评分(r=-0.459,P=0.003)均显著负相关。模型组肝脏adipoR1 mRNA表达逐步上升,adipoR2表达逐步下降,分别于4周、2周开始与对照组相比具有统计学差异(P均<0.01);肝脏adipoR2 表达与肝指数(r=-0.431,P=0.006)、纤维化评分(r=-0.353,P=0.025)均显著负相关。结论:NAFLD大鼠肝脏adipoR mRNA表达异常、血清脂联素水平降低,后者与肝脏脂肪性炎症、纤维化程度相关,提示血清脂联素降低,肝脏adipoR表达异常,尤其是adipoR2 mRNA降低与NAFLD密切相关。

    Abstract:

    Objective:To investigate the correlation of serum adiponectin and hepatic adiponectin receptor(adipoR)expression with pathological changes of the liver in the rats with non-alcoholic fatty liver diseases(NAFLD).Methods: The NAFLD model was induced by an oral administration of high fat diet.The rats were sacrificed at 2,4,8,and 12 weeks.ELISA was used to measure the serum adiponectin and other biochemical parameters.The liver index was also examined.AdipoR mRNA expression in the liver were measured by RT-PCR.Liver slices were observed with Sudan Ⅲ staining,H-E staining and Masson staining for pathological changes.Results: The serum adiponectin in the model group were gradually decreased during the 2nd,4th,8th,and 12th week,and were all significantly lower than those in the control group at corresponding time points(P<0.01).Serum adiponectin level was found negatively correlated with the liver index(r=-0.383,P=0.015),hepatic inflammation scale(r=-0.475,P=0.002),and hepatic fibrosis scale(r=-0.353,P=0.025).The hepatic adipoR1 mRNA expression in the model group was gradually increased (P<0.01 from the 4th week) and adipoR2 mRNA expression was gradually decreased compared with the control group (P<0.01 from the 2nd week). AdipoR2 mRNA expression was negative correlated with liver index(r=-0.431,P=0.006) and hepatic fibrosis scale(r=-0.353,P=0.025).Conclusion: The hepatic adipoR mRNA expression is abnormal in rats with NAFLD; the serum adiponectin level is decreased and negatively correlated with liver inflammation and fibrosis scale,indicating that the decreased serum adiponectin level,pathological hepatic adipoR expression,especially the decreased AdipoR2 expression in the liver may be related to the pathogenesis of NAFLD.

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  • 收稿日期:2008-07-19
  • 最后修改日期:2008-12-12
  • 录用日期:2008-12-20
  • 在线发布日期: 2009-01-16
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