New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

XbaⅠpolymorphisms of apolipoprotein B gene:Another risk factor of gallstone formation after radical gastrectomy

AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B (APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n =162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP).RESULTS:The incidence of gallstone was significantly higher in the X + X-group than in the X-X-group[54.2% vs 9.3%,RR=5.85(2.23-15.32),P<0.001].The serum levels of total cholesterol(TC)and low-density lipoprotein(LDL)were higher in the X + X-than in the X-X-group(4.02±1.12 vs 3.48±0.88,P=0.004 before surgery and 3.88±1.09 vs 3.40±0.86,P=0.008 after surgery).LDL was 2.21±0.96 vs 1.89±0.84(P =0.042)before surgery and 2.09±0.95 vs 1.72±0.85 (P=0.029)after surgery in the two groups.No relationship was found between XbaⅠpolymorphisms and gallbladder motility.CONCLUSION:In Chinese patients after radical gastrectomy,X + allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.

应用COBAS-FARA生化自动分析仪免疫比浊测定血清载脂蛋白A_Ⅰ及B含量的研究

在国内首次应用COBAS-FARA生化自动分析仪以免疫比浊法测定血清载脂蛋白AI及B的含量。本法批内变异为1.30%～2.02%,日间变异为2.29%～2.44%;回收率为96.05%～105.39%;载脂蛋白AI及B的检测分别在0.3g～3.0 g/L及0.1g～2.0g/L范围内呈良好的线性关系;与手工比浊法及火箭电泳法对比,其相关系数在0.9002～0.9426之间。

老年急性脑梗死患者Hcy ApoB/ApoAⅠ及动态动脉硬化指数与颈动脉斑块性质的关系分析

目的:观察老年急性脑梗死(ACI)患者同型半胱氨酸(Hcy)、载脂蛋白B(ApoB)/载脂蛋白AⅠ(ApoAⅠ)及动态动脉硬化指数(AASI)的变化与颈动脉斑块性质的关系。方法:纳入2021年7月至2023年7月本院收治的老年ACI患者103例(稳定性斑块61例,不稳定斑块42例),观察患者Hcy、ApoB/ApoAⅠ及AASI水平,采用单因素分析和多因素Logistic回归分析Hcy、ApoB、ApoAⅠ、AASI与颈动脉斑块性质的关系,并绘制受试者工作特征曲线(ROC)分析三指标对颈动脉斑块性质的评估效能。结果:不稳定斑块组Hcy、ApoB/ApoAⅠ、AASI水平及颈动脉中膜厚度(IMT)明显高于稳定斑块组,差异有统计学意义(P<0.05);Pearson相关性显示:Hcy、ApoB/ApoAⅠ、AASI水平与IMT成正相关,相关性有统计学意义(r=0.354、0.372、0.390,P<0.05);单因素分析显示:合并高血压、糖尿病、高脂血症与颈动脉斑块性质相关,差异有统计学意义(P<0.05);多因素Logistic回归分析显示:合并高血压、糖尿病、高脂血症及Hcy、ApoB/ApoAⅠ、AASI水平是影响颈动脉斑块性质的危险因素,差异有统计学意义(P<0.05);ROC分析显示:Hcy、ApoB/ApoAⅠ、AASI评估颈动脉斑块性质的AUC为0.696、0.711、0.764,三指标联合评估的AUC最高为0.853,最大约登指数下的敏感度和特异度分别为0.952、0.607。结论:老年ACI患者Hcy、ApoB/ApoAⅠ、AASI水平变化与颈动脉斑块性质存在一定的关联,且对不稳定性斑块具有一定的评估价值。

High levels of homocysteine downregulate apolipoprotein E expression via nuclear factor kappa B

AIM: To investigate the effect of high homocysteine(Hcy) levels on apolipoprotein E(apoE) expression and the signaling pathways involved in this gene regulation.METHODS: Reverse transcriptase polymerase chain reaction(RT-PCR) and Western blot were used to assess apo E expression in cells treated with various concentrations(50-500 μmol/L) of Hcy. Calcium phosphatetransient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2(ME2)]. To this aim, plasmids containing the proximal apoE promoter [(-500/+73)apoE construct] alone or in the presence of ME2 [ME2/(-500/+73)apoE construct] to drive the expression of the reporter luciferase gene were used. Co-transfection experiments were carried out to investigate the downstream effectors of Hcymediated regulation of apoE promoter by using specific inhibitors or a dominant negative form of IKβ. In other co-transfections, the luciferase reporter was under the control of synthetic promoters containing multiple specific binding sites for nuclear factor kappa B(NF-κB), activator protein-1(AP-1) or nuclear factor of activated T cells(NFAT). Chromatin immunoprecipitation(ChI P)assay was accomplished to detect the binding of NF-κB p65 subunit to the apoE promoter in HEK-293 treated with 500 μmol/L Hcy. As control, cells were incubated with similar concentration of cysteine. NF-κB p65 proteins bound to DNA were immunoprecipitated with anti-p65 antibodies and DNA was identified by PCR using primers amplifying the region-100/+4 of the apoE gene. RESULTS: RT-PCR revealed that high levels of Hcy(250-750 μmol/L) induced a 2-3 fold decrease in apoE m RNA levels in HEK-293 cells, while apo E gene expression was not significantly affected by treatment with lower concentrations of Hcy(100 μmol/L). Immunoblotting data provided additional evidence for the negative role of Hcy in apoE expression. Hcy decreased apoE promoter activity, in the presence or absence of ME2, in a dose dependent manner, in both RAW 264.7 and HEK-293 cells, as revealed by transient transfection experiments. The downstream effectors of the signaling pathways of Hcy were also investigated. The inhibitory effect of Hcy on the apo E promoter activity was counteracted by MAPK/ERK kinase 1/2(MEK1/2) inhibitor U0126, suggesting that MEK1/2 is involved in the downregulation of apoE promoter activity by Hcy. Our data demonstrated that Hcy-induced inhibition of apoE took place through activation of NF-κB. Moreover, we demonstrated that Hcy activated a synthetic promoter containing three NF-κB binding sites, but did not affect promoters containing AP-1 or NFAT binding sites. ChI P experiments revealed that NF-κB p65 subunit is recruited to the apoE promoter following Hcy treatment of cells.CONCLUSION: Hcy-induced stress negatively modulates apoE expression via MEK1/2 and NF-κB activation. The decreased apo E expression in peripheral tissues may aggravate atherosclerosis, neurodegenerative diseases and renal dysfunctions.

C-reactive Protein Level,Apolipoprotein B-to-apolipoprotein A-1 Ratio,and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China

Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.

Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion

Apolipoprotein B （apoB） is the main protein component of very low density lipoprotein （VLDL） and is necessary for the assembly and secretion of these triglyceride （TG）-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein （LDL） in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation （ERAD） by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regu- lated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autop- hagy and postprandial activation of the unfolded protein response （UPR） may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.

THE ASSOCIATION OF POLYMORPHISMS AT A VNTR LOCUS 3’TO THE APOLIPOPROTEIN B GENE WITH CORONARY HEART DISEASE IN CHINESE POPULATION

The polymorphisms of variable number of tandem repeats (VNTR) 3’to the apolipoprotein B (apo B) gene were investigated using polymerase chain reaction (PCR) in a sample of 103 patients with documented coronary heart disease (CHD) and 100 healthy individuals selected from Chinese Han nationality.Twelve segregating alleles (3’β29 -51) were observed in the pooled total of 203 subjects. The most common allele was 3’β 37. followed by 3’β39 with frequencies of 0. 362 and 0. 296, respectively. This model of allele distribution was coincident with the results form different ethnic groups, but the relative frequencies of alleles were different. In comparison with the allele frequencies between the patients and controls,alleles bigger than 3’β39 (3’VNTR-B) were significantly more common among the patients than among the controls (P<0. 001). Moreover. in the CHD group patients with plasma levels of TC≥3.88 mmol/L,LDL-C≥2. 59 mmol/L and HDL-C<l. 16mmol/L had significantly higher frequencies of 3’ VNTR-B allele (P<0. 01). Therefore,it is suggested that 3’ VNTR-B allele might be involved in the development of coronary atherosclerosis, presumably through their influences on lipid metabolism.This study supported by “8. 5” grant from Ministry of PublicHealth.

Effect of bilobalide B on cholinergic hippocampal neurons exposed to cholesterol and apolipoprotein E4

BACKGROUND： Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer＇s disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons. OBJECTIVE： To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4 DESIGN, TIME AND SETTING： This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006. MATERIALS： Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5 g were selected for this study. Cholesterol and apolipoprotein E4 （apoE4） were purchased from Sigma Company （USA）, bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312. METHODS： Hippocampal neurons were divided into three groups： a normal control group （routinely added media）, a model group （exposed to media containing 40 mg/L cholesterol and 30 mg/L apoE4 for 24 hours） and a bilobalide B group （exposed to media containing 160 mg/L bilobalide B for 16 hours, and then with addition of 40 mg/L cholesterol and 30 mg/L apoE4 for an additional 24 hours）. MAIN OUTCOME MEASURES： Levels of acetylcholine （ACh） and activity of acetylcholinesterase （ACHE） and choline acetyltransferase （CHAT） in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively. RESULTS： The ACh level was significantly lower in the model group than that in the normal control group （P 〈 0.01）, while it was markedly higher in the bilobalide B group than in the model group （P 〈 0.05）. Activity of AChE was significantly decreased in the model group compared with the normal control group （P 〈 0.05）. However, there was no significant difference between the model group and the bilobalide B group （P 〉 0.05）. Activity of ChAT was significantly lower in the model group than in the normal control group （P 〈 0.01）, while the activity was significantly higher in the bilobalide B group than in the model group （P 〈 0.05）. CONCLUSION： Bilobalide B can enhance the ACh level of hippocampal neurons damaged by combined cholesterol and apoE4, by promoting the synthesis, but not the degradation, of ACh.

心血管调节肽、载脂蛋白B/载脂蛋白AⅠ、视黄醇结合蛋白4与高钠摄入H型高血压患者发生颈动脉粥样硬化相关性

目的探讨血清心血管调节肽(salusin-β)、视黄醇结合蛋白4(RBP4)、载脂蛋白B(ApoB)/载脂蛋白AⅠ(ApoAⅠ)水平与高钠摄入H型高血压患者发生颈动脉粥样硬化的相关性。方法将石家庄市人民医院自2022年3月至2023年12月收治的105例具有高钠摄入饮食习惯且伴有颈动脉粥样硬化的H型高血压患者纳入粥样硬化组;另将同期的107例具有高钠摄入饮食习惯但不合并颈动脉粥样硬化的H型高血压患者纳入非粥样硬化组。再根据颈动脉斑块特征,将粥样硬化组分为不稳定斑块组和稳定斑块组。比较粥样硬化组和非粥样硬化组的一般资料、血压相关指标及salusin-β、RBP4、ApoB、ApoAⅠ、ApoB/ApoAⅠ水平;同时,比较不稳定斑块组和稳定斑块组的salusin-β、RBP4、ApoB、ApoAⅠ、ApoB/ApoAⅠ水平;采用Logistic回归模型分析高钠摄入H型高血压患者发生颈动脉粥样硬化的风险因素。结果粥样硬化组年龄≥60岁、合并糖尿病、合并血脂异常的比例均高于非粥样硬化组,差异有统计学意义(P<0.05)。粥样硬化组salusin-β、RBP4、ApoB、ApoB/ApoAⅠ水平均高于非粥样硬化组,差异有统计学意义(P<0.05)。在粥样硬化组的105例患者中,检出不稳定斑块62例(不稳定斑块组)、稳定斑块43例(稳定斑块组);不稳定斑块组salusin-β、RBP4、ApoB、ApoB/ApoAⅠ水平均高于稳定斑块组,差异有统计学意义(P<0.05)。粥样硬化组高血压病史长于非粥样硬化组,24h收缩压变异性大于非粥样硬化组,差异有统计学意义(P<0.05)。Salusin-β水平升高、RBP4水平升高、ApoB/ApoAⅠ水平升高、年龄≥60岁、合并糖尿病、合并血脂异常、高血压病史长、24h收缩压变异性增大是高钠摄入H型高血压患者发生颈动脉粥样硬化的危险因素(P<0.05)。结论血清salusin-β、RBP4、ApoB/ApoAⅠ水平在高钠摄入H型高血压并发颈动脉粥样硬化患者中升高,且其与颈动脉粥样硬化斑块发生及性质具有密切的相关性。

Apolipoprotein B Is a Good Tool for Screening Dyslipidaemia in Apparently Healthy Population

Dyslipidaemia is the major risk factor for cardiovascular disease (CVD) which is the leading cause of death in the world. Even though several lipid parameters are used, currently apolipoprotein B (apoB) is considered as the best predictor of CVD. Thus this study was carried out to find out the association between conventional lipid parameters and apoB in apparently healthy subjects. A descriptive cross-sectional study was carried out in 170 apparently healthy volunteers who were not diagnosed with dyslipidaemia. After 12 hours overnight fast venous blood was obtained and Total cholesterol (TC), Triglyceride (TG), High density lipoprotein cholesterol (HDL-C) were measured by enzymatic kit method. Low density lipoprotein cholesterol (LDL-C) was calculated by Friedewald formula and apoB was analyzed by immune turbid metry using a Konelab® auto analyzer. Among the participants, majority (63.5%) were females. The mean value of apoB concentration of the population was 103 ± 42 mg/dL which was similar and not significantly different between the genders (Males, 102 ± 37 mg/dL and Females, 104 ± 45 mg/dL). All lipid parameters showed a positive correlation with apoB concentration whereas HDL-C had a negative correlation (r = -0.165). HDL-C significantly (p < 0.05) decreased with increase in apoB concentration while LDL-C, TC/HDL-C and non-HDL-C significantly (p < 0.05) increased with an increase in apoB concentration. Present study suggests that serum apoB has better correlations and associations with the parameters that are used in conventional lipid profile and with markers recommended for diagnosing dyslipidaemia. Hence apoB could be used as a single marker for screening dyslipidaemia in apparently healthy people.

16层螺旋CT血管成像评价颈动脉斑块性质与载脂蛋白A-Ⅰ/载脂蛋白B关系的研究

目的应用16层螺旋CT颈部血管成像技术,探讨不同性质的斑块与载脂蛋白A-Ⅰ/载脂蛋白B(ApoA-Ⅰ/ApoB)的关系。方法选择60例缺血性脑卒中患者,常规血糖、血脂、肝肾功能、ApoA-Ⅰ、ApoB等检查,ApoA-Ⅰ/ApoB<1为观察组,ApoA-Ⅰ/ApoB≥1为对照组。均经颈部彩色多普勒检查(CDS)初步筛选颈部有无斑块。在经踝静脉注入对比剂行颈部16层螺旋CT血管造影(CTA)检查,进行后处理,观察颈部血管斑块情况,依据CT值判定斑块性质,同时与ApoA-Ⅰ/ApoB分析。结果 60例患者共发现208块斑块。颈动脉不同部位斑块性质的分布间差异有统计意义(χ2=28.62,P<0.01)。颈动脉不同部位的狭窄程度比较,差异均有统计学意义(Hc=28.62,P<0.01),其中颈总动脉起始段与颈总动脉分叉部、颈总动脉中段与颈内动脉起始段、颈总动脉分叉与颈内动脉起始段的狭窄程度比较,差异均有统计学意义(t值分别为-4.62、-3.38、2.51,P<0.01)。观察组与对照组分别比较责任病灶与非责任病灶侧血管内软斑块、中间斑块、硬斑块分布,差异均有统计学意义(Hc=3.17,Hc=3.32,P<0.05);两组责任病灶侧斑块分布比较,差异有统计学意义(Hc=15.00,P<0.01);两组非责任病灶侧斑块分布比较,差异无统计学意义(Hc=1.67,P>0.05)。结论 16层螺旋CT能够较大范围地发现颈动脉粥样斑块的分布,可对其性质、狭窄程度进行判定。ApoA-Ⅰ/ApoB<1可视为颈动脉不稳定斑块的危险度评估,作为降脂治疗的指导指标。

双生子人群apoAⅠ和apoB100水平及遗传度分析

目的:描述双生子人群的apoAⅠ、apoB100水平,并探讨遗传和环境因素对其水平的影响程度。方法:选择双生子502对,采用免疫透射比浊法检测血清apoAⅠ、apoB100水平。在基因法卵性鉴定的基础上,结合年龄和性别因素,用最大似然法在Mx程序包进行遗传模型拟合。结果:本双生子人群包括同卵双生子329对,异卵双生子173对。apoAⅠ水平为(1.33±0.23)g/L,apoB100水平为(0.75±0.19)g/L。apoAⅠ的最适模型为AES模型,apoB100的最适模型为等级效应性别限制AE模型。遗传方差在apoAⅠ中所占的比重为60%;在apoB100中所占的比重为69%。结论:在本双生子人群中,apoAⅠ的遗传度为60%,apoB100的遗传度为69%。

载脂蛋白A-Ⅰ通过PKA信号途径影响ABCA1的表达与功能

以THP-1巨噬细胞源性泡沫细胞为研究对象,观察载脂蛋白A-Ⅰ与三磷酸腺苷结合盒转运体A1(ATP binding cassette transporter A1,ABCA1)的相互作用,并探讨它们相互作用的机制,以便了解载脂蛋白A-Ⅰ和ABCA1在动脉粥样硬化发生发展中的作用.THP-1巨噬细胞源性泡沫细胞经各种因素处理后,采用油红“O”染色,观察细胞内的脂滴,运用液体闪烁计数器检测细胞内胆固醇流出,高效液相色谱分析细胞内总胆固醇、游离胆固醇和胆固醇酯含量,用逆转录-聚合酶链反应和蛋白质印迹分析法分别检测ABCA1 mRNA与ABCA1蛋白质的水平.实验结果显示,载脂蛋白A-Ⅰ和腺苷酸环化酶激动剂Forskolin(FRK)引起THP-1巨噬细胞源性泡沫细胞总胆固醇、游离胆固醇与胆固醇酯减少,而腺苷酸环化酶抑制剂SQ-22536引起THP-1巨噬细胞源性泡沫细胞总胆固醇、游离胆固醇与胆固醇酯增加.载脂蛋白A-Ⅰ引起THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平和细胞内胆固醇流出增加.FRK引起THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平和细胞内胆固醇流出呈时间和浓度依赖性增加.SQ-22536引起THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平和细胞内胆固醇流出减少.结果提示,载脂蛋白A-Ⅰ可提高THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平,增加细胞内胆固醇流出,降低细胞内胆固醇聚积.其机制可能是通过PKA信号途经使细胞ABCA1蛋白质水平增加.

急性心肌梗死患者ApoB/ApoAⅠ比值与颈动脉斑块类型的关系

目的探讨急性心肌梗死患者血清载脂蛋白B(Apo B)、载脂蛋白AⅠ(Apo AⅠ)水平及其比值与颈动脉粥样硬化斑块类型的关系。方法对65例急性心肌梗死患者(病变组)及36例冠状动脉正常者(对照组)行颈动脉超声检查及Apo B、Apo AⅠ水平测定,计算Apo B/Apo AⅠ比值。根据超声检查结果将所有患者颈动脉斑块分为软斑块、纤维斑块、钙化斑块,对各种数据进行统计学分析。结果病变组软斑块的检出率明显高于对照组(P<0.001),病变组载脂蛋白B水平、Apo B/Apo AⅠ比值均高于对照组(P<0.05);病变组中软斑块者载脂蛋白B水平、Apo B/Apo AⅠ比值较纤维斑块者和钙化斑块者高(P<0.05);对照组中软斑块者载脂蛋白B水平、Apo B/Apo AⅠ比值较纤维斑块者高(P<0.01)。载脂蛋白B、Apo B/Apo AⅠ比值对软斑块的诊断均有较好的准确性,ROC曲线下面积分别为0.753±0.067、0.701±0.071。结论载脂蛋白B、Apo B/Apo AⅠ比值及斑块类型与急性心肌梗死密切相关,载脂蛋白B、Apo B/Apo AⅠ比值与以颈动脉超声检测为标准的斑块类型有关。

阻塞型睡眠呼吸暂停低通气综合征与ApoB/ApoAⅠ的相关性分析

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与ApoB/ApoAⅠ的相关性。方法收集单纯鼾症患者29例,OSAHS患者50例的基本信息及甘油三酯(TG)、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)、LDL-C/HDL-C、ApoAⅠ、ApoB、ApoB/ApoAⅠ、血糖(Glu)、血尿酸(UA)、睡眠监测结果。结果 OSAHS组血ApoB/ApoAⅠ、BMI较对照组明显增加(P<0.05),两组TG、TC、HDL-C、LDL-C、LDL-C/HDL-C、ApoAⅠ、ApoB、Glu、UA、年龄、性别、口服降脂药情况差异均无统计学意义(P>0.05)。并且,ApoB、ApoB/ApoAⅠ、BMI与呼吸暂停低通气指数(AHI)呈正相关(r=0.243、0.298、0.281,P<0.05)。结论肥胖是OSAHS的重要危险因素,并且BMI与AHI呈正相关。OSAHS患者与单纯鼾症患者相比血ApoB/ApoAⅠ明显升高,并且血ApoB、ApoB/ApoAⅠ与OSAHS严重程度正相关。

饮用纯净水对大鼠肝脏载脂蛋白AⅠ和B基因表达的影响

目的 观察饮用纯净水及加镁纯净水对大鼠肝脏载脂蛋白AⅠ和载脂蛋白B基因表达的影响,探讨纯净水致血脂异常的作用机制。方法 健康Wistar大鼠60只,随机分为自来水组(对照组)、纯净水组和加镁纯净水组(纯净水+0 5g LMgSO4 ·7H2 O) ,每组2 0只。大鼠饲养至6个月时处死,取肝脏用RT PCR法检测肝脏apoAⅠ、apoBmRNA表达量。结果 饮用纯净水可使大鼠肝脏apoBmRNA表达水平升高,肝脏apoAⅠmRNA表达水平下降,但无显著性差异;加镁纯净水组大鼠肝脏apoAⅠmRNA表达水平,比单纯饮用纯净水组上升,肝脏apoBmRNA水平与纯净水组比有下降,但无显著性差异。结论 提示肝脏apoAⅠ、apoB转录水平的表达可能不是纯净水致血脂异常的主要调控因素,可能存在转录后水平或肝外组织的调控,其作用机制尚待进一步研究。

载脂蛋白B/载脂蛋白AⅠ与颈动脉斑块稳定性及狭窄程度的关系

目的探讨载脂蛋白B（Apo B）/载脂蛋白AⅠ（Apo AⅠ）与颈动脉斑块稳定性及狭窄程度的关系。方法采用超声多普勒检查1089例颈动脉硬化患者的颈动脉情况,并检测患者的血脂水平。采用Logistic回归分析Apo B/Apo AⅠ与颈动脉斑块稳定性及颈动脉狭窄程度的关系。结果与非不稳定斑块患者比较,不稳定斑块患者男性、吸烟、饮酒史比率及舒张压、收缩压、Apo B/Apo AⅠ、糖化血红蛋白、低密度脂蛋白（LDL）/高密度脂蛋白（HDL）水平显著升高,HDL、Apo AⅠ水平显著降低（P〈0.05∽0.01）。多因素Logistic回归显示,性别、舒张压、饮酒及Apo B/Apo AⅠ为发生不稳定斑块的独立危险因素（P〈0.05--0.01）,而Apo AⅠ为独立保护因素（P〈0.01）。与狭窄程度≤50%的患者比较,狭窄程度〉50%患者的男性、年龄、吸烟史、饮酒史、糖尿病、冠心病史比率及收缩压、LDL/HDL、Apo B/Apo AⅠ、Hb A1c、Apo B水平显著升高,Apo AⅠ、HDL水平显著降低（P〈0.05∽0.01）。多因素Logistic回归显示,性别、年龄、收缩压、吸烟、冠心病史及Apo B/Apo AⅠ为发生严重颈动脉狭窄独立危险因素（P〈0.05∽0.01）。ROC曲线分析显示,Apo B/Apo AⅠ预测不稳定斑块最佳诊断分界点值为0.81,敏感度为65.0,特异度为57.0（95%CI：0.60∽0.67,P=0.000）;预测严重颈动脉狭窄的最佳诊断分界点值为0.88,敏感度为58.7,特异度为66.2（95%CI：0.60∽0.67,P=0.000）。结论Apo B/Apo AⅠ是发生颈动脉不稳定斑块及严重狭窄程度的独立危险因素。

多囊卵巢综合征患者血清apoB/apoAⅠ比值对代谢综合征的诊断价值

目的探讨多囊卵巢综合征(PCOS)患者apoB/apoAⅠ比值对代谢综合征(MS)的诊断价值。方法收集185例符合2003年鹿特丹诊断标准的PCOS患者,采集病史并对其进行体格测量和性激素、糖脂代谢等各项生化指标测定。结果 MS患病率为19.46%,而至少合并一项MS组分异常的患病率则为56.76%;apoB/apoAⅠ比值与体重指数(BMI)、低密度脂蛋白胆固醇(LDL-C)水平呈正相关,与高密度脂蛋白胆固醇(HDL-C)水平呈负相关,且随着MS组分异常项数的增加而升高;以0.66为截断值时,apoB/apoAⅠ比值对MS的诊断价值较高(敏感度为0.917,特异性为0.700)。结论 PCOS患者的apoB/apoAⅠ对MS有较好的诊断和监测价值。

Apo B和Apo AⅠ/Apo B比值在家族性高胆固醇血症与家族性混合型高脂血症鉴别诊断中的作用

目的分析家族性高胆固醇血症(FH)家系与家族性混合型高脂血症(FCHL)家系成员之间血脂水平及肾功能指标的差异,探寻用于FH和FCHL鉴别诊断的指标。方法收集符合诊断标准的FH家系6个(共47人),FCHL家系23个(共94人),正常对照组家系10个(共57人),在FH家系和FCHL家系内又分为血脂升高的受累组和血脂正常的未受累组,比较各组之间的血脂水平和肾功能指标(包括CO2CP、BUN、Cr、BUN/Cr、UA)。结果 FH家系受累组TC、HDL-C、LDL-C及Apo B水平均明显高于未受累组和对照组,Apo AⅠ/Apo B比值明显低于未受累组和对照组,LP(a)、BUN和Cr水平也高于未受累组和对照组,TAG水平高于未受累组和对照组,差异均有统计学意义。FCHL家系受累组TC、TAG、LDL-C及Apo B水平均明显高于未受累组和对照组,HDL-C水平高于未受累组和对照组,Apo AⅠ/Apo B比值明显低于未受累组和对照组,LP(a)和BUN水平也高于对照组,差异均有统计学意义。2个家系受累组间相比,FH家系LDL-C和Apo B水平明显高于FCHL家系,TC水平和Apo AⅠ/Apo B比值也高于FCHL家系,而TAG水平明显低于FCHL家系。结论除常用的TC、TAG和LDL-C之外,Apo B和Apo AⅠ/Apo B有望成为FH与FCHL鉴别诊断的指标。