CAJ | 학술논문

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.
목적 관찰재지단백E (ApoE)모의태ApoE23대세균성농독혈증소서혈장지다당(LPS)질량농도변화적영향급기대간장저밀도지단백수체(LDLR)표체적조절작용.방법 설계ApoE모의태(ApoE23)병채용고상합성법진행합성,고효액상색보(HPLC)기술대합성물진행순화,전리자질보대합성물진행감정병대합성물진행안기산조성분석;B조서상한사문씨균유도C57BL세균성농독혈증모형병대감염소서미정맥주사ApoE23진행치료.소서혈장LPS질량농도측정채용련속투사면역비탁법.채용정량RT-PCR기술급Western blot기술검측소서간장중LDLRmRNA급단백질표체수평적변화.결과 세균성농독혈증소서혈장LPS농도현저승고,간장LDLR표체명현강저.ApoE23치료명현강저세균성농독혈증소서혈장LPS농도,병사세균감염도치적소서간장LDLR mRNA화단백질저표체득도명현규정.결론 ApoE23가능시일충잠재적항세균성농독혈증약물,기작용궤제가능여기조해간장LDLR표체유관.
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.