載脂蛋白E及其受體在細(xì)菌感染性疾病中表達(dá)變化
發(fā)布時(shí)間：2019-01-28 21:18
【摘要】：研究目的： 1、研究血清載脂蛋白E(ApoE)在兒童不同病原微生物感染性疾病中的變化。 2、研究細(xì)菌性膿毒血癥小鼠肝臟ApoE及其受體表達(dá)變化來初步探討膿毒血癥時(shí)血清ApoE升高的原因。 研究方法： 1、將臨床已明確診斷為細(xì)菌性膿毒血癥、化膿性腦膜炎、無菌性腦膜、細(xì)菌性肺炎和支原體肺炎患兒納入研究對象,將非感染的健康體檢兒童納入對照組。除常規(guī)實(shí)驗(yàn)室檢驗(yàn)指標(biāo),如外周血白細(xì)胞計(jì)數(shù)(WBC)、C反應(yīng)蛋白(CRP)、腦脊液(CSF)、血液標(biāo)本細(xì)菌培養(yǎng)鑒定、血清肺炎支原體IgM檢測、CSF腸道病毒RNA定量PCR檢測外,血清ApoE濃度采用透射免疫比濁法測定。 2、采用B組鼠傷寒沙門菌誘導(dǎo)膿毒血癥C57BL小鼠模型,研究膿毒血癥小鼠血清ApoE濃度和肝臟ApoE表達(dá)變化特點(diǎn)。通過檢測膿毒血癥小鼠肝臟ApoE代謝受體：低密度脂蛋白受體(LDLR)、多配體蛋白聚糖-1(SDC1)和低密度脂蛋白受體相關(guān)蛋白(LRP)表達(dá)變化初步了解膿毒血癥時(shí)ApoE變化機(jī)制。 研究結(jié)果 1、共有337位兒童入組,其中診斷為細(xì)菌性膿毒血癥患兒65例、化膿性腦膜炎患兒47例、細(xì)菌性肺炎患兒67例、無菌性腦膜炎患兒47例及支原體肺炎患兒53例,對照組58例,年齡范圍(0-6歲,平均2.9歲)。細(xì)菌性膿毒血癥、化膿性腦膜炎和細(xì)菌性肺炎患兒血清ApoE水平分別為5.98±2.35mg/dL、5.07±1.48mg/dL、4.63±1.32mg/dL,均高于對照組(3.37±0.98) mg/dL(P0.05)。無菌性腦膜炎(3.62±0.97mg/dL)和肺炎支原體肺炎(3.35±1.02mg/dL)患者血清ApoE濃度與對照組比較變化不明顯(P0.05)。 2、膿毒血癥組小鼠腹腔注射B組鼠傷寒沙門菌后1h血液培養(yǎng)即分離到B組鼠傷寒沙門細(xì)菌。血清LPS水平在感染后1h已開始升高,感染后3小時(shí)及24小時(shí)已顯著高于對照組。膿毒血癥組小鼠血漿ApoE濃度在感染后1h、3h及24小時(shí)均高于對照組小鼠。 3、膿毒血癥小鼠肝臟ApoE mRNA及蛋白質(zhì)表達(dá)在感染后1h無明顯變化,感染后3h和24h與對照組相比表達(dá)明顯下降。 4、與對照組小鼠相比,膿毒血癥小鼠肝臟LDLR mRNA及蛋白質(zhì)表達(dá)在感染后1h、3h、24h均顯著下降。膿毒血癥小鼠肝臟SDC1mRNA及蛋白質(zhì)表達(dá)僅在感染后1h下降,感染后3h及24h無變化。膿毒血癥小鼠肝臟LRP mRNA及蛋白質(zhì)表達(dá)在感染1h、3h表達(dá)下降,感染后24h無表達(dá)不明顯。 結(jié)論 1、血清ApoE升高是細(xì)菌感染一種生物標(biāo)記,其升高幅度與感染范圍有關(guān)。其臨床診斷價(jià)值有待進(jìn)一步研究。 2、盡管膿毒血癥小鼠肝臟ApoE表達(dá)下降,但由于肝臟ApoE代謝受體LDLR,SDC1,LRP表達(dá)降低阻礙了肝臟對ApoE代謝,其最終結(jié)果使膿毒血癥小鼠血漿ApoE水平升高。這為細(xì)菌性膿毒血癥治療提供新靶點(diǎn)
[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 鹵2.35mg / dL 5.07 鹵1.48mg / dL 4.63 鹵1.32mg / dL, respectively, which were higher than those in the control group (3.37 鹵0.98) mg/dL (P0.05). Serum ApoE levels in patients with aseptic meningitis (3.62 鹵0.97mg/dL) and mycoplasma pneumoniae pneumonia (3.35 鹵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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.16
本文編號(hào)：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 鹵2.35mg / dL 5.07 鹵1.48mg / dL 4.63 鹵1.32mg / dL, respectively, which were higher than those in the control group (3.37 鹵0.98) mg/dL (P0.05). Serum ApoE levels in patients with aseptic meningitis (3.62 鹵0.97mg/dL) and mycoplasma pneumoniae pneumonia (3.35 鹵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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.16
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