乙型肝炎病毒对载脂蛋白B表达的影响及其机制探讨

目的 探讨乙型肝炎病毒(HBV)对载脂蛋白B(ApoB)表达的影响,并探讨其调节机制.方法 采用RT-PCR和Western blot法检测HepG2和HepG2.2.15中ApoB mRNA和蛋白的表达,全自动生化分析仪Olympus 5400检测HBV患者和健康对照者ApoB血清学水平,分析健康对照者、慢性乙型肝炎、肝纤维化和肝癌患者中ApoB表达水平的差异,将HBV感染性克隆pHBV1.3转染HepG2细胞,RT-PCR和Western blot法检测ApoB和微粒体甘油三酯转移蛋白(MTP)表达水平的变化.结果 HepG2.2.15细胞中ApoB mRNA和蛋白的表达水平较HepG2低;ApoB在慢性乙型肝炎患者和肝纤维化患者的血清学水平明显低于健康对照者(P＜0.05);HBV能够在mRNA和蛋白水平抑制ApoB和MTP的表达.结论 HBV可能通过抑制MTP的表达抑制ApoB的合成和分泌.

Abstract：

Objective To explore the effect of hepatitis B virus(HBV) on the expression of apolipoprotein B(ApoB) and its regulatory mechanism. Methods mRNA and protein expression of ApoB in HepG2 and HepG2.2.15 cells was measured by RT-PCR and Western blot, serum ApoB levels in patients with HBV infection and in healthy individuals were measured by biochemical analyzer Olympus 5400, the expression of ApoB difference among healthy individuals, patients with chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma were analyzed, HBV infectious clone pHBV1.3 was tranfected into HepG2 cells,and expression of ApoB and microsomal triglyceride transfer protein(MTP) was measured by RT-PCR and Western blot. Results Expression of ApoB mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells, serum apoB levels was much lower in patients with chronic hepatitis B and liver cirrhosis as compared to healthy individuals( P ＜0.05 ), HBV could inhibit the expression of ApoB and MTP at mRNA and protein levels. Conclusion HBV may downregulate the synthesis and secretion of ApoB via inhibits the expression of MTP.     

抗人血清载脂蛋白B100单克隆抗体的制备及鉴定

低致度脂蛋LDL中98%以上为载脂蛋白B100(ApoB100)。许多研究表明LDL含量与动脉硬化、冠心病呈正相关。高水平ApoB是致动脉硬化的主要原因。     

极低密度脂蛋白的肝内装配——小分子量的载脂蛋白B的磷酸化

新生的极低密度脂蛋白(VLDL)颗粒赖以装配并继而定向通过分泌囊泡,这种多细胞器的通路穿梭至胞外的分子向相互作用尚不明了。载脂蛋白B(ApoB)至少以两种类型存在。一些实验结果提示,VLDL的装配需要一种或二种分子量类型的ApoB。但是由于在研究ApoB方面的技术上的问题,诸如自身相联以及水溶液中不能维持其溶解性等原因,故对其结构、顺序以及化学组成所知甚少,而且限于不充分的化学资料,对于ApoB指导VLDL装配和分泌的独特的分子特性仍不清楚。     

人ApoB基因的限制性片段长度多态性

动脉粥样硬化(AS)是多因素疾病,遗传易感是其中的因素,载脂蛋白基因的变异与AS密切相关,本文着重讨论ApoB基因的限制性片段长度多态性(RFLP)与ApoB抗原、及其与AS的关系。     

健康成人、高血压病、心绞痛和陈旧心梗患者血脂及载脂蛋白的对比定量研究

本文报告山东省西部四地市健康成人(393例)、高血压病(317例)、心绞痛(191例)和陈旧心梗(84例)患者血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、载脂蛋白(Apo)A-I和B浓度,并计算HDL-C/TC、HDL-C/LDL-C和ApoA-I/ApoB。结果表明:各疾病     

人和大鼠发育期间体内ApoB mRNA编辑的个体发育调节

脂类的溶解和运输依靠两种形式的ApoB,即ApoB100和ApoB48。这两个蛋白质是同一ApoB基因的翻译产物。在ApoB mRNA经历转录后的C→U转变,使得密码子CAA(谷氨酰胺,2153)转变为终止密码子UAA后,它就只能编码ApoB48了。这一转录后加工过程,称为ApoB mRNA编辑。在     

检测血脂及血清ApoB/ApoA1比值对冠状动脉粥样硬化临床诊断意义

目的 探究血脂及血清生化指标载脂蛋白B(ApoB)与载脂蛋白A(ApoA1)比值ApoB/ApoA1在冠状动脉粥样硬化临床诊断中的应用价值.方法 选取我院2018年3月至2019年10月收治的冠状动脉粥样硬化患者98例为观察组,同期于我院健康体检者102例为对照组.检测两组研究对象血脂及血清生化指标,分析ApoB/ApoA1及血脂相关生化指标数据.结果 观察组患者的TG、TC、LDL-C、Lp(a)、LDL-C/HDL-C比值均明显高于对照组,HDL-C明显低于对照组,差异均具有统计学意义(P<0.05).观察组血清ApoB及ApoB/ApoA1比值均明显高于对照组,ApoA1明显低于对照组,差异均具有统计学意义(P<0.05).ApoB/ApoA1比值与TG、TC、LDL-C、Lp(a)及LDL-C/HDL-C呈统计学正相关(r值分别为0.328、0.441、0.615、0.331、0.569,P<0.05);与HDL-C呈统计学负相关(r=-0.572,P<0.05);与LDL-C、HDL-C、LDL-C/HDL-C比值呈较强相关性(P<0.05).多元线性逐步回归分析显示ApoB/ApoA1与Lp(a)、LDL-C/HDL-C一致为冠状动脉粥样硬化危险因素(P<0.01),且均与冠状动脉粥样硬化成正相关.结论 ApoB/ApoA1比值可为冠状动脉粥样硬化的临床诊断生物标志物,可对冠状动脉粥样硬化的诊疗提供参考.     

ApoB100基因第26号外显子6694bp处MspⅠ位点突变与高血脂相关性

目的:载脂蛋白B100(ApoB100)是血浆中低密度脂蛋白(LDL)的组成成分,可与组织中LDL受体结合并介导LDL的降解和清除,此功能对于维持血清中LDL和胆固醇水平的稳定起重要作用.ApoB100的一些基因突变将明显影响ApoB100的结构和功能,导致血浆中LDL降解受阻,血浆中LDL和胆固醇含量升高从而增加其它心血管疾病的风险.本文将探讨ApoB100基因第26号外显子6694bp处的基因突变所致的MspⅠ位点多态性与高血脂之间的关系.方法:本文采用KI法提取50例高血脂症患者、60例对照组人群外周血细胞基因组DNA,设计并合成PCR引物,利用聚合酶链式反应-限制性片段长度多态性方法(PCR-RFLP)分析其ApoB100基因第26号外显子6694bp处MspⅠ位点的基因型.结果:高血脂组基因型分布为M(+)M(+)∶42例,M(+)M(-)∶7例,M(-)M(-)∶1例;对照组基因型分布为M(+)M(+)∶59例,M(+)M(-)∶1例,M(-)M(-)∶0例.统计分析表明高血脂组与对照组之间基因型分布有明显差异(P＜0.05).结论:ApoB100基因第26号外显子6694bp处MspⅠ位点突变与高血脂相关.     

雌性食蟹猴月经周期中雌二醇、孕酮水平的变化及其与血脂的关系

观察雌性食蟹猴月经周期中雌二醇、孕酮水平的变化及其与血脂的相关性,并将其变化规律与育龄妇女月经周期中的雌二醇、孕酮变化规律相比较.选取20只性成熟雌性食蟹猴测定其血清雌二醇(E2)、孕酮(P)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白Al(ApoAl)和载脂蛋白B(ApoB)的水平,历时31～51天.观察其中6只在月经期、卵泡期、排卵期及黄体期的E2、P、TC、TG、HDL-C、ApoAl和ApoB水平的变化.结果显示,雌性食蟹猴的E2与TC、ApoAl、ApoB呈正相关,与TG、HDL-C呈负相关;P与TG、ApoB呈正相关,与HDL-C呈负相关.卵泡期E2水平最高,黄体期P水平最高.雌性食蟹猴月经周期中E2、P水平的变化与血脂水平的变化之间存在动态平衡.其E2、P变化规律与育龄妇女月经周期中的变化规律相似,可能为探讨雌性激素与血脂变化的关系及其对心血管疾病的影响提供动物试验的基础资料.     

ApoB100基因第26号外显子6694bp处MspⅠ位点突变与高血脂相关性g

目的：载脂蛋白B100（ApoB100）是血浆中低密度脂蛋白（LDL）的组成成分,可与组织中LDL受体结合并介导LDL的降解和清除,此功能对于维持血清中LDL和胆固醇水平的稳定起重要作用。ApoB100的一些基因突变将明显影响ApoB100的结构和功能,导致血浆中LDL降解受阻,血浆中LDL和胆固醇含量升高从而增加其它心血管疾病的风险。本文将探讨ApoB100基因第26号外显子6694bp处的基因突变所致的MspⅠ位点多态性与高血脂之间的关系。方法：本文采用KI法提取50例高血脂症患者、60例对照组人群外周血细胞基因组DNA,设计并合成PCR引物,利用聚合酶链式反应-限制性片段长度多态性方法（PCR-RFLP）分析其ApoB100基因第26号外显子6694bp处MspⅠ位点的基因型。结果：高血脂组基因型分布为M（＋）M（＋）：42例,M（＋）M（-）：7例,M（-）M（-）：1例;对照组基因型分布为M（＋）M（＋）：59例,M（＋）M（-）：1例,M（-）M（-）：0例。统计分析表明高血脂组与对照组之间基因型分布有明显差异（P〈0.05）。结论：ApoB100基因第26号外显子6694bp处MspⅠ位点突变与高血脂相关。     

Apolipoprotein A-I,apolipoprotein B,high-sensitivity C-reactive protein and severity of coronary artery disease in tunisian population

BackgroundThe relationship between Apolipoprotein A-I, Apolipoprotein B, C-reactive protein and the severity coronary artery disease in Tunisian CAD patients has not been examined. We investigated the association between serum ApoA-I, ApoB, hs-CRP and the severity of coronary artery disease.MethodsThis study was carried out on 180 patients who underwent angiography and 129 healthy controls. ApoA-I and ApoB as well as the serum total cholesterol, HDL, triglyceride, LDL and hs-CRP levels were measured. The ApoB/ApoA-I ratio was calculated.ResultsWe showed a decreased level of ApoA-I and an increased level of ApoB, ApoB/ApoA-I ratio and hs-CRP in CAD patients compared to the control group (P<.001). In addition, we showed a significant increase of ApoB, ApoB/ApoA-I ratio and hs-CRP in CAD patients presenting 0 to 3 vessels stenosis (P<.001). Multivariate analysis showed that ApoB (P<.001), and hs-CRP (P<.001) were independent predictors of the severity of CAD.ConclusionIn this study, ApoB and hs-CRP levels were markedly associated with the severity of CAD in Tunisian patients. We suggested that synergistic effects between dyslipidemia and inflammation led to increase the risk of the severity of CAD.     

ApoB/ApoA-I ratio in young patients with ischemic cerebral stroke or peripheral arterial disease

Although smoking and hypertension are classic risk factors for atherothrombotic diseases, the relationship of dyslipidemia and vascular diseases, other than myocardial infarction, is less clearly established, especially in young subjects. In the current study, a detailed analysis of the lipid and apolipoprotein profiles was conducted in young patients of ischemic cerebral stroke (IS) and peripheral arterial disease (PAD). Plasma levels of C-reactive protein (hs-CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), and apolipoproteins A-I (ApoA-I) and apolipoproteins B (ApoB), which include the ApoB/ApoA-I ratio, were analyzed in a group of 81 patients who presented with IS (n = 46) or PAD (n = 35) as well as in 167 control subjects. Significant differences were observed for hs-CRP, TC, HDLc, LDLc, TG, ApoA-I, and ApoB levels, as well as for the ApoB/ApoA-I ratio, between the control and the IS or PAD groups. However, after adjustment for sex, age, smoking, hypertension, hs-CRP, and dyslipidemia (LDLc, TC, HDLc, TG, ApoA, ApoB, and ApoB/ApoA-I ratio), hs-CRP, ApoB, and the ApoB/ApoA-I ratio were independently associated with increased risks of IS or PAD. Increased ApoB/ApoA-I ratio and hs-CRP levels are independently associated with occurrence of IS and PAD in young patients and are significant markers of alterations on lipid and apolipoproteic profiles and inflammatory responses, respectively, in these patients.     

补阳还五汤加减治疗冠心病对血脂和雌二醇代谢的影响

目的:探讨补阳还五汤加减治疗冠心病血脂和雌二醇(E2)代谢的变化。方法:49例冠心病患者服用补阳还五汤加减治疗两个月,应用酶法检测治疗前后的总胆固醇(TC)、甘油三脂(TG),均相酶法检测高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),免疫透射比浊法检测载脂蛋白A1(ApoA1)和载脂蛋白B(ApoB),化学发光免疫法检测雌二醇(E2)。结果:治疗后TC、LDL-C、ApoB降低,ApoA1升高,与治疗前比较差异有显著性意义(P<0.05),TG、HDL-C、E2治疗前后比较无统计学差异(P>0.05)。结论:补阳还五汤加减治疗冠心病有助于改善血脂代谢。     

Association between epitopes detected by monoclonal antibody BIP-45 and the Xbal polymorphism of Apolipoprotein B

An epitope of Apolipoprotein B (ApoB), recognised by a monoclonal antibody BIP-45, is associated with the development of ischaemic heart disease (Duriez et al. 1988). We have examined the genetic relationships between this epitope and three Restriction Fragment Length Polymorphisms (RFLPs) of the gene for ApoB detected with the enzymes EcoRI, PvuII and XbaI in a sample of 53 unrelated individuals from France. There is an association between binding affinity to BIP-45 and the XbaI RFLP; the 8.6 kb XbaI allele (absence of cutting site) being associated with low-affinity binding to BIP-45. In this sample of individuals there is no significant association between serum cholesterol levels and BIP-45 binding affinity, but there is a significant correlation between serum cholesterol levels and XbaI genotype, with individuals of the genotype X1X1 having the highest and those with the genotype X2X2 having the lowest levels of serum cholesterol. This suggests that variation at the ApoB locus may be involved independently in the determination of serum lipid levels and in the development of ischaemic heart disease.     

Einbau von15N-Glyzin in VLDL und LDL: In-vivo-Synthese von Apolipoprotein B beim Menschen postabsorptiv und im Fastenzustand

Summary In vivo synthesis of apolipoprotein B 100 (ApoB) was recently determined in man using stable isotopes. With this procedure we analyzed (1) the effect of fasting on synthesis of ApoB from very low density lipoprotein (VLDL) and (2) tracer enrichment in low density lipoprotein (LDL).After a 36-hour fasting period and in the post-absorptive state 4 healthy subjects were given a priming dose (8.7 µmol/kg) of¹⁵N glycine followed by a constant infusion (10 µmol/kg/h for 8 h) to achieve 5% tracer enrichment in the plasma pool of glycine. The K-values, i.e. fractional synthetic rates/hr of ApoB from VLDL were 0.53±0.26 vs. 0.43±0.16 (p>0.05). Tracer enrichment in ApoB from LDL at the end of the infusions was 0.19% vs. 1.46% in ApoB from VLDL.The results indicate that (1) in young healthy postabsorptive individuals about 40% of ApoB from VLDL in plasma is synthesized per hour, (2) fasting does not materially affect fractional ApoB synthesis and (3) at 5%¹⁵N enrichment in plasma glycine, tracer enrichment in ApoB from LDL is at the lower limit of detection for the procedure employed.

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Abkürzungen ApoB Apolipoprotein B 100 - LDL low density lipoprotein - VLDL very low density lipoprotein - ISV Ionenstrom-Verhältnis - SIM selected ion monitoring - APZ Atom-Prozent-Zunahme     

Escherichia coli lipopolysaccharide may affect the endothelial barrier and IL-10 expression of apolipoprotein B100-pulsed dendritic cells

Atherogenesis is associated with chronic gut infections; however, the mechanisms are not clear. The aim of the study was to determine whether lipopolysaccharide of E. coli (E. coli LPS) may affect endothelial barrier and modify IL-10 expression in dendritic cells (DCs). Human umbilical vein endothelial cells (HUVECs) and monocyte-derived DCs were treated with E. coli LPS, apolipoprotein B100 (ApoB100) and 7-ketocholesterol (7-kCH) – harmful oxidized form of cholesterol. The effect of E. coli LPS, 7-kCH and ApoB100 on the barrier functions of HUVECs in real-time cell electric impedance sensing system (RTCA-DP) was assessed. Furthermore, the effect of 7-kCH and ApoB100 on barrier functions of HUVECs co-cultured with DCs previously treated with LPS was analyzed. Both E. coli LPS and 7-kCH decreased barrier functions of HUVECs and reduced tight junction protein mRNA expression, whereas ApoB100 increased endothelial barrier. In DCs, ApoB100 and E. coli LPS decreased IL-10 mRNA expression. In HUVECs co-cultured with DCs treated with LPS and subsequently pulsed with ApoB100 or 7-kCH, IL-10 mRNA expression was lower. E. coli LPS-exposed DCs diminished the protective effect of ApoB100 on endothelial integrity and led to the decrease in occludin mRNA expression. LPS potentially derived from gut microflora may destabilize endothelial barrier together with oxidized cholesterol and intensify the immunogenicity of ApoB100.     

血清同型半胱氨酸检测的临床意义回顾分析

为探讨血清同型半胱氨酸(THCY)检测的临床意义,回顾性分析173例心脑血管疾病或糖尿病患者和31名正常人血清THCY水平与其Folate,VB12,Glu,CH,Tg,ApoA,ApoB,HDL-CH,LDL-CH水平及所患疾病的关系。结果表明,血清THCY与Folate,VB12浓度呈负相关,与Glu,CH,Tg,ApoA,ApoB,HDL-CH,LDL-CH无明显的相关性。动脉硬化性心血管疾病患者及糖尿病患者的血清THCY浓度明显高于对照组。血清THCY是动脉硬化性心血管疾病及糖尿病的危险因子。Folate,VB12补充疗法可降低血清THCY,可能成为动脉硬化性心血管疾病及糖尿病患者高血THCY血症的治疗方案。