载脂蛋白E及其受体在细菌感染性疾病中表达变化
发布时间：2019-01-28 21:18
【摘要】：研究目的： 1、研究血清载脂蛋白E(ApoE)在儿童不同病原微生物感染性疾病中的变化。 2、研究细菌性脓毒血症小鼠肝脏ApoE及其受体表达变化来初步探讨脓毒血症时血清ApoE升高的原因。 研究方法： 1、将临床已明确诊断为细菌性脓毒血症、化脓性脑膜炎、无菌性脑膜、细菌性肺炎和支原体肺炎患儿纳入研究对象,将非感染的健康体检儿童纳入对照组。除常规实验室检验指标,如外周血白细胞计数(WBC)、C反应蛋白(CRP)、脑脊液(CSF)、血液标本细菌培养鉴定、血清肺炎支原体IgM检测、CSF肠道病毒RNA定量PCR检测外,血清ApoE浓度采用透射免疫比浊法测定。 2、采用B组鼠伤寒沙门菌诱导脓毒血症C57BL小鼠模型,研究脓毒血症小鼠血清ApoE浓度和肝脏ApoE表达变化特点。通过检测脓毒血症小鼠肝脏ApoE代谢受体：低密度脂蛋白受体(LDLR)、多配体蛋白聚糖-1(SDC1)和低密度脂蛋白受体相关蛋白(LRP)表达变化初步了解脓毒血症时ApoE变化机制。 研究结果 1、共有337位儿童入组,其中诊断为细菌性脓毒血症患儿65例、化脓性脑膜炎患儿47例、细菌性肺炎患儿67例、无菌性脑膜炎患儿47例及支原体肺炎患儿53例,对照组58例,年龄范围(0-6岁,平均2.9岁)。细菌性脓毒血症、化脓性脑膜炎和细菌性肺炎患儿血清ApoE水平分别为5.98±2.35mg/dL、5.07±1.48mg/dL、4.63±1.32mg/dL,均高于对照组(3.37±0.98) mg/dL(P0.05)。无菌性脑膜炎(3.62±0.97mg/dL)和肺炎支原体肺炎(3.35±1.02mg/dL)患者血清ApoE浓度与对照组比较变化不明显(P0.05)。 2、脓毒血症组小鼠腹腔注射B组鼠伤寒沙门菌后1h血液培养即分离到B组鼠伤寒沙门细菌。血清LPS水平在感染后1h已开始升高,感染后3小时及24小时已显著高于对照组。脓毒血症组小鼠血浆ApoE浓度在感染后1h、3h及24小时均高于对照组小鼠。 3、脓毒血症小鼠肝脏ApoE mRNA及蛋白质表达在感染后1h无明显变化,感染后3h和24h与对照组相比表达明显下降。 4、与对照组小鼠相比,脓毒血症小鼠肝脏LDLR mRNA及蛋白质表达在感染后1h、3h、24h均显著下降。脓毒血症小鼠肝脏SDC1mRNA及蛋白质表达仅在感染后1h下降,感染后3h及24h无变化。脓毒血症小鼠肝脏LRP mRNA及蛋白质表达在感染1h、3h表达下降,感染后24h无表达不明显。 结论 1、血清ApoE升高是细菌感染一种生物标记,其升高幅度与感染范围有关。其临床诊断价值有待进一步研究。 2、尽管脓毒血症小鼠肝脏ApoE表达下降,但由于肝脏ApoE代谢受体LDLR,SDC1,LRP表达降低阻碍了肝脏对ApoE代谢,其最终结果使脓毒血症小鼠血浆ApoE水平升高。这为细菌性脓毒血症治疗提供新靶点
[Abstract]:Objective: 1. To study the changes of serum apolipoprotein E (ApoE) in children with different pathogenic microbiological infectious diseases. 2. To study the expression of ApoE and its receptor in the liver of mice with bacterial sepsis, and to explore the causes of the increase of serum ApoE during sepsis. Methods: 1. Children with bacterial sepsis, suppurative meningitis, aseptic meninges, bacterial pneumonia and mycoplasma pneumonia were included in the study. In addition to routine laboratory tests, such as peripheral blood leukocyte count, (WBC), C reactive protein (CRP), cerebrospinal fluid (CSF) (CSF), bacterial culture, serum mycoplasma pneumoniae IgM, CSF enterovirus RNA quantitative PCR, Serum ApoE concentration was determined by transmission immunoturbidimetry. 2. The C57BL model of sepsis induced by Salmonella typhimurium in group B was used to study the changes of serum ApoE concentration and liver ApoE expression in sepsis mice. The changes of ApoE metabolic receptor (ApoE), low density lipoprotein receptor (LDLR),) polyligand proteoglycan 1 (SDC1) and low density lipoprotein receptor associated protein (LRP) (LRP) in the liver of sepsis mice were investigated. Results 1. A total of 337 children were enrolled, including 65 children with bacterial sepsis, 47 with suppurative meningitis, 67 with bacterial pneumonia, 47 with aseptic meningitis and 53 with mycoplasma pneumonia. 58 cases in the control group, the age range (0-6 years, average 2.9 years). The serum ApoE levels in children with bacterial sepsis, suppurative meningitis and bacterial pneumonia were 5.98 卤2.35mg / dL 5.07 卤1.48mg / dL 4.63 卤1.32mg / dL, respectively, which were higher than those in the control group (3.37 卤0.98) mg/dL (P0.05). Serum ApoE levels in patients with aseptic meningitis (3.62 卤0.97mg/dL) and mycoplasma pneumoniae pneumonia (3.35 卤1.02mg/dL) were not significantly different from those in the control group (P0.05). 2. Salmonella typhimurium was isolated from mice of group B after intraperitoneal injection of Salmonella typhimurium in group B. The serum LPS level began to increase at 1 h after infection and was significantly higher than that in the control group at 3 h and 24 h after infection. The concentration of plasma ApoE in sepsis group was higher than that in control group at 3 h and 24 h after infection. 3. The expression of ApoE mRNA and protein in the liver of sepsis mice did not change at 1 h after infection, but decreased significantly at 3 h and 24 h after infection as compared with the control group. 4. Compared with the control group, the expression of LDLR mRNA and protein in the liver of sepsis mice decreased significantly at 1h, 3h and 24h after infection. The expression of SDC1mRNA and protein in the liver of sepsis mice only decreased at 1 h after infection, but did not change at 3 h and 24 h after infection. The expression of LRP mRNA and protein in the liver of sepsis mice decreased at 1h and 3h after infection, but there was no obvious expression at 24 h after infection. Conclusion 1. The increase of serum ApoE is a biomarker of bacterial infection, and the extent of increase is related to the range of infection. Its clinical diagnostic value needs further study. 2. Although the expression of ApoE in the liver of sepsis mice decreased, the decrease of LDLR,SDC1,LRP expression of ApoE metabolic receptor in the liver hindered the metabolism of ApoE in the liver, which resulted in the increase of plasma ApoE level in sepsis mice. This provides a new target for the treatment of bacterial sepsis.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.16
本文编号：2417325
[Abstract]:Objective: 1. To study the changes of serum apolipoprotein E (ApoE) in children with different pathogenic microbiological infectious diseases. 2. To study the expression of ApoE and its receptor in the liver of mice with bacterial sepsis, and to explore the causes of the increase of serum ApoE during sepsis. Methods: 1. Children with bacterial sepsis, suppurative meningitis, aseptic meninges, bacterial pneumonia and mycoplasma pneumonia were included in the study. In addition to routine laboratory tests, such as peripheral blood leukocyte count, (WBC), C reactive protein (CRP), cerebrospinal fluid (CSF) (CSF), bacterial culture, serum mycoplasma pneumoniae IgM, CSF enterovirus RNA quantitative PCR, Serum ApoE concentration was determined by transmission immunoturbidimetry. 2. The C57BL model of sepsis induced by Salmonella typhimurium in group B was used to study the changes of serum ApoE concentration and liver ApoE expression in sepsis mice. The changes of ApoE metabolic receptor (ApoE), low density lipoprotein receptor (LDLR),) polyligand proteoglycan 1 (SDC1) and low density lipoprotein receptor associated protein (LRP) (LRP) in the liver of sepsis mice were investigated. Results 1. A total of 337 children were enrolled, including 65 children with bacterial sepsis, 47 with suppurative meningitis, 67 with bacterial pneumonia, 47 with aseptic meningitis and 53 with mycoplasma pneumonia. 58 cases in the control group, the age range (0-6 years, average 2.9 years). The serum ApoE levels in children with bacterial sepsis, suppurative meningitis and bacterial pneumonia were 5.98 卤2.35mg / dL 5.07 卤1.48mg / dL 4.63 卤1.32mg / dL, respectively, which were higher than those in the control group (3.37 卤0.98) mg/dL (P0.05). Serum ApoE levels in patients with aseptic meningitis (3.62 卤0.97mg/dL) and mycoplasma pneumoniae pneumonia (3.35 卤1.02mg/dL) were not significantly different from those in the control group (P0.05). 2. Salmonella typhimurium was isolated from mice of group B after intraperitoneal injection of Salmonella typhimurium in group B. The serum LPS level began to increase at 1 h after infection and was significantly higher than that in the control group at 3 h and 24 h after infection. The concentration of plasma ApoE in sepsis group was higher than that in control group at 3 h and 24 h after infection. 3. The expression of ApoE mRNA and protein in the liver of sepsis mice did not change at 1 h after infection, but decreased significantly at 3 h and 24 h after infection as compared with the control group. 4. Compared with the control group, the expression of LDLR mRNA and protein in the liver of sepsis mice decreased significantly at 1h, 3h and 24h after infection. The expression of SDC1mRNA and protein in the liver of sepsis mice only decreased at 1 h after infection, but did not change at 3 h and 24 h after infection. The expression of LRP mRNA and protein in the liver of sepsis mice decreased at 1h and 3h after infection, but there was no obvious expression at 24 h after infection. Conclusion 1. The increase of serum ApoE is a biomarker of bacterial infection, and the extent of increase is related to the range of infection. Its clinical diagnostic value needs further study. 2. Although the expression of ApoE in the liver of sepsis mice decreased, the decrease of LDLR,SDC1,LRP expression of ApoE metabolic receptor in the liver hindered the metabolism of ApoE in the liver, which resulted in the increase of plasma ApoE level in sepsis mice. This provides a new target for the treatment of bacterial sepsis.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.16
【参考文献】
相关期刊论文 前4条
1 王璇;李爱敏;初清;;感染性疾病急性期反应蛋白的研究进展[J];山东医药;2010年45期
2 葛青玮,高原,黄洁;高敏感C反应蛋白检测在新生儿感染性疾病中的应用[J];上海医学检验杂志;2002年04期
3 王艳;载脂蛋白E与遗传性病和感染性疾病的关系[J];山西医科大学学报;2004年01期
4 方丽波;王拥军;张星虎;李明慧;刘广志;;多发性硬化的免疫遗传学研究进展[J];中国康复理论与实践;2007年01期
，本文编号：2417325
本文链接：https://www.wllwen.com/yixuelunwen/jsb/2417325.html
最近更新
教材专著
