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早期肝脂肪变性中 caveolin-1 的分布改变。

Altered distribution of caveolin-1 in early liver steatosis.

机构信息

Department of Animal and Environmental Biology, Aldo Moro University, Bari, Italy.

出版信息

Eur J Clin Invest. 2011 Jun;41(6):642-51. doi: 10.1111/j.1365-2362.2010.02459.x. Epub 2011 Jan 20.

Abstract

BACKGROUND

Caveolin-1, the main structural protein of caveolae, is involved in cholesterol homoeostasis, transcytosis, endocytosis and signal transduction and thought to play an important role in lipidogenesis. Little is known about the pathophysiological role of caveolin-1 in nonalcoholic fatty liver disease (NAFLD), a condition frequently associated with the metabolic syndrome and characterized by abnormal accumulation of intrahepatic triglycerides with a potentially harmful risk of evolution to liver fibrosis, cirrhosis and hepatocellular carcinoma.

MATERIALS AND METHODS

Liver steatosis (micro/macrovesicular) was induced in adult rats fed a choline-deficient diet for 14days and compared with a control normal diet. The expression and subcellular distribution of caveolin-1 was assessed using light and electron microscopy by immunohistochemical and immunocytochemical techniques and by Western blotting.

RESULTS

Caveolin-1 was mainly associated with the hepatocyte basolateral plasma membrane. Fatty hepatocytes were characterized by a significant increase in the expression of caveolin-1 around and within the lipid droplets as well as in the inner membrane of mitochondria.

CONCLUSIONS

Our data suggest the involvement of caveolin-1 in the case of abnormal lipogenesis and mitochondrial function typical of steatotic hepatocytes in NAFLD. Addressing the role played by caveolin-1 in liver membranes in NAFLD may help future therapeutic choices in a frequent metabolic liver disease.

摘要

背景

窖蛋白-1 是质膜窖的主要结构蛋白,参与胆固醇稳态、转胞吞作用、内吞作用和信号转导,被认为在脂生成中发挥重要作用。关于窖蛋白-1 在非酒精性脂肪性肝病(NAFLD)中的病理生理作用知之甚少,这种疾病常与代谢综合征相关,其特征是肝内甘油三酯异常积聚,具有向肝纤维化、肝硬化和肝细胞癌发展的潜在有害风险。

材料和方法

用胆碱缺乏饮食喂养成年大鼠 14 天诱导肝脂肪变性(微泡/大泡性),并与正常对照饮食进行比较。用免疫组织化学和免疫细胞化学技术以及 Western 印迹法通过光镜和电镜评估窖蛋白-1 的表达和亚细胞分布。

结果

窖蛋白-1 主要与肝细胞基底外侧质膜相关。脂肪变性的肝细胞特征是脂质滴周围和内部以及线粒体内膜的窖蛋白-1表达显著增加。

结论

我们的数据表明,窖蛋白-1 参与了非酒精性脂肪性肝病中典型的脂肪生成异常和线粒体功能障碍。研究窖蛋白-1 在 NAFLD 肝细胞膜中的作用可能有助于未来在这种常见的代谢性肝病中选择治疗方法。

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