The Variance Of Apolipoprotein E And Apolipoprotein E Receptors Expression Associated With Bacterial Infection

Objective1. To determine the variation of serum Apolipoprotein E (ApoE) in children with infectious diseases caused by distinct pathogens.2. To investigate the potential mechanisms of serum ApoE changes in sepsis by detectingthe expression of the hepatic ApoE and ApoE receptors in septic mice.Methods1. Pediatric patients with confirmed bacterial sepsis, bacterial meningitis, bacterial pneumonia, aseptic meningitis and Mycoplasma pneumonia were enrolled in this study.While the subjects from physical examination center without any confirmable infections were served as control. The investigative data including the C-reactive protein levels in the peripheral blood, the peripheral blood white blood cell counts (WBC), the CSF routine tests and the CSF biochemical examination were determined by routine laboratroy tests. The microbiological analysis were performed via bacterial culture for blood and CSF samples. The Mycoplasma-Pneumoniae IgM measurment and enterovirus RNA detection were accomplished in the serum samples and the CSF samples, respectively. ApoE levels in serum were measured by immunoturbidimetry2. The sepsis in C57BL mice model were established by peritoneal cavity injection of Salmonella typhimurium group B.The serum ApoE levels were detected at different time point after bacterial injection. In order to explore the potential mechanisms associated with the changes of serum apoE levels in the septic mice, the ApoE and ApoE receptors (LDLR, SDC1, LRP) expression in the hepar of sepsis mice were measured by real time PCR and western blot.Results1. A total of337pediatric patients (aged from0to6year,2.9year for average) were enrolled in this study. The cases were sub-classified into five groups:65patients with sepsis,47patients with bacterial meningitis,67patients with bacterial pneumonia,47patients with aseptic meningitis,53patients with Mycoplasma pneumonia and58subjects without infections were set as control group. The serum ApoE levels in patients suffered from bacterial infection were5.98±2.35mg/dL in the bacterial sepsis group,5.07±1.48mg/dL in the patients with bacterial meningitis, and4.63±1.32mg/dL in the patients with bacterial pneumonia, all of which were higher than that in control group (3.37±0.98mg/dL, P<0.05). However, no significant difference were found in patients with aseptic meningitis (3.62±0.97mg/dL) and Mycoplasma pneumonia (3.35±1.02mg/dL)2. One hours after the live Salmonella typhimurium groups B were inculated by peritoneal cavity injection in the C57BL mice, the Salmonella typhimurium groups B were isolated in the blood of the septic mice. Compared with the control group, the plasma LPS levels in the septic mice were slightly higher at the1h after infection and followed by dramatical increase at the3h and24h after inoculation. The plasma ApoE levels in the septic mice were also found slightly increased at the three time points compared with control group.3. The expression of the hepatic ApoE mRNA and protein levels in the septic mice showed no significant difference compared with control at1h after inoculation. However, the hepatic ApoE expression in the septic mice decreased significantly at3h and24h after injection respectively.5. Compared with the control group, the hepatic LDLR mRNA and protein expressions in the septic mice remarkably decreased at1h,3h, and24h after inoculation respectively. The hepatic SDC1mRNA and protein expression were found to be decreased only at1h after inoculation in the septic mice. The hepatic LRP mRNA and protein expression in the septic mice were found to be decreased both at1h and3h after infection.Conclusions1. The Serum ApoE is a specific biological maker for the bacterial infection. The range of variation is related with the extent of bacterial infection. The potential diagnostic value of ApoE examination for prediction of bacterial infection is worthy of further study.2. Althogh the reduced expression of ApoE in the hepar in sepsis, the plasma ApoE levels were found to be increased caused by the down expression of hepatic LDLR,LRP and SDC1, which probably contributes to ApoE accumulations in plasma in sepsis. This study may provide a novel therapeutic target for treating this disease.