中文摘要：

目的：研究感染和炎症时前蛋白转化酶枯草溶菌素9（proprotein convertase subtilisin/kexin type 9,PCSK9）在调节血浆低密度脂蛋白胆固醇（low density lipoprotein cholesterol,LDL-C）代谢中的作用及其可能的分子机制。方法：用全自动生化仪监测小鼠血浆总胆固醇、高密度脂蛋白胆固醇、甘油三酯、磷脂以及谷氨酸氨基转移酶含量。同时,用快速液相色谱（fast proteinliquid chromatography,FPLC）分析混合的小鼠血浆。血浆淀粉样蛋白A（serum amyloid A,SAA）浓度用酶联免疫吸附法测定。用定量PCR法检测肝脏组织的PCSK9、LDL受体等脂代谢相关基因mRNA丰度,并用Western blot分析肝组织中LDL受体表达变化。结果：研究发现低剂量脂多糖（liposacaridica,LPS）注射24 h后血浆谷氨酸氨基转移酶无明显变化,小鼠血浆LDL-C增高43.02%,高密度脂蛋白胆固醇增高30.09%、甘油三酯增高27.21%,磷脂增高25.50%。LPS注射组动物的血浆SAA明显增多至（1 271.05±94.13）ng/ml,增多的SAA主要与高密度脂蛋白和低密度脂蛋白结合。LPS处理诱导肝脏PCSK9基因表达上调,抑制肝脏LDL受体的蛋白表达。结论：研究表明LPS引起肝细胞中PCSK9上调,LDL受体蛋白表达受抑制,同时小鼠血浆LDL-C迅速增多,提示PCSK9抑制LDL受体通路可能通过影响血浆脂蛋白代谢在炎症导致的宿主反应中起重要作用。

英文摘要：

Objective：To study the effect of PCSK9 on the LDL-C metabolism in response to infection and inflammation.Methods：C57B / 6J male mice were injected with low dose liposaccharide（LPS） to mimic acute phase responce.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 decreased 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.