载脂蛋白E模拟肽ApoE23对细菌性脓毒血症小鼠血浆脂多糖浓度的影响及机制研究  

The effect and mechanism of an apolipoprotein E mimetic peptide ApoE23 on plasma lipopolysaccharide levels in the septic mice

作　　者：殷丽军[1] 王传清[1] 杨昌生[2] 付盼[1] 王爱敏[1] 

机构地区：[1]复旦大学附属儿科医院院感科,细菌室,上海201102 [2]复旦大学附属中山医院心内科

出　　处：《中华急诊医学杂志》2014年第11期1234-1238,共5页Chinese Journal of Emergency Medicine

基　　金：上海市科委自然科学研究基金（08ZR1401800）

摘　　要：目的 观察载脂蛋白E （ApoE）模拟肽ApoE23对细菌性脓毒血症小鼠血浆脂多糖（LPS）质量浓度变化的影响及其对肝脏低密度脂蛋白受体（LDLR）表达的调节作用.方法 设计ApoE模拟肽（ApoE23）并采用固相合成法进行合成,高效液相色谱（HPLC）技术对合成物进行纯化,电离子质谱对合成物进行鉴定并对合成物进行氨基酸组成分析;B组鼠伤寒沙门氏菌诱导C57BL细菌性脓毒血症模型并对感染小鼠尾静脉注射ApoE23进行治疗.小鼠血浆LPS质量浓度测定采用连续透射免疫比浊法.采用定量RT-PCR技术及Western blot技术检测小鼠肝脏中LDLRmRNA及蛋白质表达水平的变化.结果 细菌性脓毒血症小鼠血浆LPS浓度显著升高,肝脏LDLR表达明显降低.ApoE23治疗明显降低细菌性脓毒血症小鼠血浆LPS浓度,并使细菌感染导致的小鼠肝脏LDLR mRNA和蛋白质低表达得到明显纠正.结论 ApoE23可能是一种潜在的抗细菌性脓毒血症药物,其作用机制可能与其调解肝脏LDLR表达有关.Objective To observe the effect of apolipoprotein E mimetic peptide （ApoE23） on lipopolysaccharide （LPS） levels in plasma and the regulatory role of ApoE23 on low density lipoprotein receptor （LDLR） on liver cells in the septic mice.Methods An ApoE mimetic peptide was designed and referred terminologically as ApoE23 in abbreviation.ApoE23 was synthesized by using solid phase synthesis assay and were refined by using high performance liquid chromatography （HPLC）.The peptide was identified and confirmed by using electron spray ionization mass spectrometry and amino acid composition analysis.The C57BL mice infected with Salmonella typhimurium group B were treated with apoE23 injected into tail vein.The plasma LPS levels were measured by using immunoturbidimetry.The LDLR expression and level on liver cells were measured by real time PCR and western blot respectively.Results The plasma LPS levels significantly increased and the liver LDLR expression decreased in the septic mice.ApoE23 treatment markedly reduced the plasma LPS levels and redressed the LDLR down-expressions on liver cells both in mRNA and protein levels compared to the septic mice without ApoE23 treatment.Conclusions The reduction of LPS level after ApoE23 treatment may be associated with the modulation role of ApoE23 in LDLR expression on liver cells,and ApoE23 may be a potential agent against bacterial sepsis as well.One of possible mechanisms was most likely associated with effect of ApoE23 on LDLR expression.

关 键 词：载脂蛋白E 载脂蛋白E模拟肽 细菌性脓毒血症 脂多糖 低密度脂蛋白受体 

分 类 号：R459.7[医药卫生—急诊医学]