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脂多糖上调小鼠肝脏PCSK9升高血浆低密度脂蛋白胆固醇

李晓宇 单清 李楠 杨清 何龙

南京医科大学学报(自然科学版)2011,Vol.31Issue(12):1726-1730,5.
南京医科大学学报(自然科学版)2011,Vol.31Issue(12):1726-1730,5.

脂多糖上调小鼠肝脏PCSK9升高血浆低密度脂蛋白胆固醇

Serum LDL-C increased by PCSK9 in LPS-treated mice model

李晓宇 1单清 2李楠 1杨清 1何龙1

作者信息

  • 1. 南京医科大学病理生理学系,江苏省心血管病分子干预重点实验室,江苏南京210029
  • 2. 扬州市第一人民医院,江苏扬州225001
  • 折叠

摘要

Abstract

Objective: To study the effect of PCSK9 on the LDL-C metabolism in response to infection and inflammation. Meth ods :C57B/6J male mice were injected with low dose liposaccharide (LPS) to mimic acute phase response. Plasma lipids levels were detected. Serum amyloid A levels in peripheral circulation and purified fast protein liquid chromatography (FPLC) fractions have been assayed by ELISA. Real time PCR has been used to measure PCSK9,LDLR ,HMGR and other genes mRNA level in mice liver. Results: Low dose LPS treatment induced abundant serum amyloid A secretion and marked changes in lipid and lipoprotein metabolism, including high total cholesterol and triglyceride levels. We explored the effect of LPS on PCSK9 expression, and found LPS resulted in a marked increase in hepatic PCSK9 mRNA levels (2.88-fold increase). Furthermore,we demonstrated that LPS de creased hepatic LDL receptor protein but at the same time hepatic LDL receptor mRNA levels were not decreased. Conclusion: Thus PCSK9 expression stimulated by inflammation led to increased LDL receptor degradation and decreased LDL receptors, and thereby increased serum LDL. The results suggest that proinflammatory states,such as those associated with obesity and insulin resistance, may be associated with upregulated hepatic expression of PCSK9.

关键词

PCSK9/炎症/低密度脂蛋白/胆固醇

Key words

PCSK9/ inflammation/ LDL/ cholesterol

分类

医药卫生

引用本文复制引用

李晓宇,单清,李楠,杨清,何龙..脂多糖上调小鼠肝脏PCSK9升高血浆低密度脂蛋白胆固醇[J].南京医科大学学报(自然科学版),2011,31(12):1726-1730,5.

基金项目

国家自然科学基金资助(81100857) (81100857)

南京医科大学学报(自然科学版)

OA北大核心CSCDCSTPCD

1007-4368

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