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Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke
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作者 Shuai Feng Juanji Li +6 位作者 Tingting Liu Shiqi Huang Xiangliang Chen Shen Liu Junshan Zhou Hongdong Zhao Ye Hong 《Neural Regeneration Research》 SCIE CAS 2025年第2期491-502,共12页
Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit... Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke. 展开更多
关键词 inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome POLARIZATION
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Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria 被引量:1
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作者 Yiyan Zhao Weimin Liu +6 位作者 Xiaoming Zhao Zhitao Yu Hongfang Guo Yang Yang Hans Merzendorfer Kun Yan Zhu Jianzhen Zhang 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第5期1618-1633,共16页
Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero... Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts. 展开更多
关键词 Locusta migratoria low-density lipoprotein receptor-related protein 2 MIDGUT lipids transport RNAi
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Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation
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作者 Renan Dal-Fabbro Minzhi Yu +3 位作者 Ling Mei Hajime Sasaki Anna Schwendeman Marco C.Bottino 《International Journal of Oral Science》 SCIE CAS CSCD 2024年第3期460-470,共11页
Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affectin... Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation. 展开更多
关键词 INFLAMMATION lipoprotein markedly
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Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity
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作者 Jun-feng ZHANG Feng-qing CAI +1 位作者 Xiu-cai ZHANG Qing YE 《Current Medical Science》 SCIE CAS 2024年第4期692-697,共6页
Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various infla... Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity. 展开更多
关键词 nonalcoholic fatty liver disease OBESITY monocyte-to-high-density lipoprotein ratio MARKER
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Initial decrease in the lipoprotein(a)level is a novel prognostic biomarker in patients with acute coronary syndrome
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作者 Yasuhiko Saeki Jun Sawaguchi +7 位作者 Satori Akita Taka-aki Takamura Kosuke Fujibayashi Minoru Wakasa Hironobu Akao Michihiko Kitayama Yasuyuki Kawai Kouji Kajinami 《World Journal of Cardiology》 2024年第6期329-338,共10页
BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)level... BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular events.METHODS From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were enrolled.Lp(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after PCI.The primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent MACE.CONCLUSION Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis. 展开更多
关键词 lipoprotein(a) Acute coronary syndrome Percutaneous coronary intervention Major adverse cardiac events PROGNOSIS
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Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus
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作者 Xiao-Ye Duan Jun-Ling Fu +2 位作者 Li-Na Sun Zhi-Jing Mu Shuang-Ling Xiu 《World Journal of Diabetes》 SCIE 2024年第10期2081-2092,共12页
BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has... BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM. 展开更多
关键词 Non-high-density lipoprotein cholesterol Sensitivity to thyroid hormones Type 2 diabetes mellitus Thyroid feedback quantile-based index Free triiodothyronine/free thyroxine ratio
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Correlation of Helicobacter pylori infection with high-density lipoprotein cholesterol levels and pulse wave conduction velocity
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作者 Yue-Xi Li Xiao-Qin Liu +1 位作者 Yu-Han Luo Qiao-Li Wang 《Clinical Research Communications》 2024年第4期33-38,共6页
Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's dise... Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's disease.However,the relationship between HP and lipid metabolism and atherosclerosis remains unclear.This study aims to investigate the association between H.pylori infection and high-density lipoprotein cholesterol levels and pulse wave conduction velocity.Methods:This is a report of a cross-sectional study that collected data from 2,827 participants.The data collected included results of life questionnaires,laboratory tests,13C-urea breath test(13C-UBT),and pulse wave conduction velocity test.Based on the results of the 13C-UBT test,the subjects were divided into two groups:the HP-uninfected group(HP−)and the HP-infected group(HP+).The study compared the differences in HDL-C levels and brachial-ankle pulse wave velocity(baPWV)between the two groups.One-way regression analysis was used to identify potential factors affecting HDL-C levels in the study population.Multiple regression equations were presented to analyze whether HP infection was an independent risk factor for abnormal HDL-C metabolism in the population.Results:Univariate analysis demonstrated that high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the HP+group compared to the HP−group,with a mean difference ofβ=−18.1 mg/dl(95%CI:−19.3 to−17.0,P<0.001).After adjusting for all variables,the HDL-C levels remained lower in the HP+group compared to the HP-group,with a mean difference ofβ=−17.4 mg/dl(95%CI:−18.2 to−16.7,P<0.001).These findings suggest that H.pylori infection is independently associated with abnormal HDL-C metabolism.Additionally,brachial-ankle pulse wave velocity(baPWV)was higher in the HP+group than in the HP−group on both sides.On the right side,the baPWV was 1,713.4±231.4 cm/s in the HP+group compared to 1,542.8±237.5 cm/s in the HP−group(t=−18.30,P<0.001).On the left side,the baPWV was 1,743.7±238.8 cm/s in the HP+group compared to 1,562.8±256.3 cm/s in the HP−group(t=−18.23,P<0.001).These results indicate a significant association between H.pylori infection and increased arterial stiffness,as measured by baPWV.Conclusion:Helicobacter pylori infection is associated with a decrease in high-density lipoprotein cholesterol levels and an increase in pulse wave conduction velocity. 展开更多
关键词 Helicobacter pylori CHOLESTEROL high-density lipoprotein ATHEROSCLEROSIS
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基于NOD样受体3炎性小体通路对利拉鲁肽在氧化低密度脂蛋白诱导内皮细胞损伤的作用机制研究
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作者 陈玲 徐锐 +2 位作者 程新春 张占英 徐红 《中国全科医学》 CAS 北大核心 2025年第5期601-606,共6页
背景动脉粥样硬化是世界范围内引起心脑血管疾病最主要的原因,炎症是目前研究热点,其中NOD样受体3(NLRP3)是研究最为深入的炎症小体。胰高糖素样肽1(GLP-1)受体激动剂有抗动脉粥样硬化作用,具体机制尚不明确。目的研究利拉鲁肽通过拮抗... 背景动脉粥样硬化是世界范围内引起心脑血管疾病最主要的原因,炎症是目前研究热点,其中NOD样受体3(NLRP3)是研究最为深入的炎症小体。胰高糖素样肽1(GLP-1)受体激动剂有抗动脉粥样硬化作用,具体机制尚不明确。目的研究利拉鲁肽通过拮抗氧化低密度脂蛋白(ox-LDL)诱导的内皮细胞损伤的作用机制。方法2022-03-25—05-19培养人脐静脉内皮细胞(HUVEC),取HUVEC加空白血清作为对照组,100μg/mL的ox-LDL干预HUVEC 48 h作为模型组,100μg/mL的ox-LDL干预HUVEC 24 h后分别加入100、200、400 nmol/L利拉鲁肽处理24 h作为利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组。CCK-8法计算细胞增殖率。通过扫描电镜观察焦亡细胞形态。检测乳酸脱氢酶(LDH)活力。酶联免疫吸附试验(ELISA)检测白介素(IL)-1β、IL-18表达水平。蛋白质免疫印迹试验(Western blot)检测NLRP3、接头蛋白凋亡相关斑点样蛋白(ASC)、天冬氨酸蛋白水解酶1(Caspase-1)、焦亡执行蛋白(GSDMD)、N端结构域的焦亡执行蛋白(N-GSDMD)表达水平。结果模型组、利拉鲁肽低浓度组和利拉鲁肽中浓度组细胞增殖率低于对照组,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组细胞增殖率高于模型组(P<0.05)。细胞扫描电镜结果示模型组细胞焦亡明显,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组细胞焦亡情况明显改善。模型组、利拉鲁肽低浓度组LDH活力高于对照组,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组低于模型组(P<0.05)。模型组、利拉鲁肽低浓度组IL-1β表达水平高于对照组,利拉鲁肽中浓度组、利拉鲁肽高浓度组IL-1β表达水平低于模型组(P<0.05);模型组IL-18表达水平高于对照组,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组IL-18表达水平低于模型组(P<0.05)。模型组NLRP3、ASC、Caspase-1、GSDMD、N-GSDMD表达水平高于对照组,利拉鲁肽低浓度组ASC、Caspase-1表达水平高于对照组,利拉鲁肽中浓度组NLRP3、ASC表达水平低于模型组,利拉鲁肽高浓度组NLRP3、ASC、Caspase-1表达水平低于模型组(P<0.05)。结论利拉鲁肽显著抑制ox-LDL诱导的内皮细胞NLRP3炎性小体活化,并且能够抑制内皮细胞的焦亡,具有抗动脉粥样硬化作用。 展开更多
关键词 动脉粥样硬化 利拉鲁肽 内皮细胞 氧化低密度脂蛋白 NOD样受体3
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阿司匹林抵抗和脂蛋白相关磷脂酶A2与复发性缺血性脑卒中的相关性分析
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作者 刘庆杰 杨璨宇 查文文 《中国实用神经疾病杂志》 2025年第1期83-87,共5页
目的探讨非心源性卒中患者阿司匹林抵抗和脂蛋白相关磷脂酶A2(Lp-PLA2)与缺血性脑卒中复发的相关性。方法选取2021-10—2022-10在永城市人民医院住院的发病7 d内的急性非心源性缺血性脑卒中患者72例,基于临床病史和神经影像学证据分为... 目的探讨非心源性卒中患者阿司匹林抵抗和脂蛋白相关磷脂酶A2(Lp-PLA2)与缺血性脑卒中复发的相关性。方法选取2021-10—2022-10在永城市人民医院住院的发病7 d内的急性非心源性缺血性脑卒中患者72例,基于临床病史和神经影像学证据分为初发组(n=36)和复发组(n=36),入院后规律服用阿司匹林7 d。采用血栓弹力图测定阿司匹林抵抗,并测定血清Lp-PLA2水平。比较初发组和复发组阿司匹林抵抗、Lp-PLA2水平,分析阿司匹林抵抗、Lp-PLA2与缺血性脑卒中复发之间的相关性。采用多元Logistic回归分析筛选复发性卒中独立危险因素,ROC曲线下面积评价相关危险因素的预测价值。结果36.1%的复发性卒中患者存在阿司匹林抵抗,19.4%的初发患者存在阿司匹林抵抗,2组比较差异有统计学意义(P<0.001)。复发性卒中患者血清PLA2水平中位数160.0μg/L,初次发病患者为125.0μg/L,2组比较差异有统计学意义(P=0.008)。多元Logistic回归分析显示阿司匹林抵抗和高PLA2水平是复发性缺血性脑卒中的影响因素,阿司匹林抵抗患者卒中复发风险增加4.06倍(P=0.042),高于Lp-PLA2中位值患者的4.37倍(P=0.011)。阿司匹林抵抗和Lp-PLA2预测卒中复发的ROC曲线下面积分别为0.753(95%CI:0.641~0.873)和0.683(95%CI:0.559~0.807)。结论与初发卒中患者相比,复发性卒中患者阿司匹林抵抗的比率和血清Lp-PLA2水平均明显升高,可作为复发性卒中的预测因素。 展开更多
关键词 复发性缺血性脑卒中 阿司匹林抵抗 血栓弹力图 脂蛋白相关磷脂酶A2 血清
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Genetic Screening of the Lipoprotein Lipase Gene for Mutations in Chinese Subjects with or without Hypertriglyceridemia 被引量:3
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作者 杨宇虹 穆云祥 +4 位作者 赵郁 刘新宇 赵莉莉 汪军梅 解用虹 《Journal of Genetics and Genomics》 SCIE CAS CSCD 北大核心 2007年第5期381-391,共11页
Objective: To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG). Methods: The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese sub... Objective: To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG). Methods: The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese subjects with (108 cases in the HTG group) or without HTG (278 cases in the control group), by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Results: One novel silent mutation L103L, one missense mutation P207L, three splicing mutations Int3/3' -ass/C(-6)→T, and the common S447X polymorphism has been identified in the whole coding region and exon-intron junctions of the LPL gene were examined. Heterozygous P207L found in the HTG group was the first case reported in Asia and subsequently another P207L heterozygote was found in the proband's family, all of which suggested that P207L was one of the causes of familial combined hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3'-ass/C(-6)→T was found in both groups in the present study although it was regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial polymorphism S447X, there was also some supportive evidence that the levels of triglycerides (TG) in S447X carriers were significantly lower than noncarders in the subjects without HTG. Conclusions: The association between the LPL variants and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale screening should be necessary and justifiable. 展开更多
关键词 lipoprotein lipase MUTATIONS CHINESE HYPERTRIGLYCERIDEMIA
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Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment
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作者 Yi Wang Yuning Li +6 位作者 Yakun Gu Wei Ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji Jia Liu 《Neural Regeneration Research》 SCIE CAS 2025年第9期2598-2610,共13页
Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to... Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment. 展开更多
关键词 BIOMARKER high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment
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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance
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作者 Beibei Wu Yuqing Liu +4 位作者 Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng 《Neural Regeneration Research》 SCIE CAS 2025年第3期695-714,共20页
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar... Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease. 展开更多
关键词 ABCA1 Alzheimer's disease AMYLOID-BETA apolipoprotein E cholesterol metabolism LIVER liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid
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Homozygous phytosterolemia and a literature review:A case report
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作者 Chun-Xin Jiang Guang Yang +1 位作者 Lian-Ping Shi Peng-Yu Su 《World Journal of Clinical Cases》 SCIE 2025年第10期46-52,共7页
BACKGROUND Phytosterolemia,also known as sitosterolemia,is a rare autosomal recessive disease characterized by elevated plasma plant sterol levels and xanthomata,which is easily misdiagnosed as familial hypercholester... BACKGROUND Phytosterolemia,also known as sitosterolemia,is a rare autosomal recessive disease characterized by elevated plasma plant sterol levels and xanthomata,which is easily misdiagnosed as familial hypercholesterolemia.Patients with homozygous phytosterolemia often have severe clinical manifestations,with xanthomata in childhood and premature atherosclerosis.Our patient had a milder clinical phenotype.CASE SUMMARY This report describes a patient with homozygous phytosterolemia who presented with only elevated cholesterol and low-density lipoprotein cholesterol(LDL-C)without xanthomata,arteriosclerosis,or hematological abnormalities.Homozygous mutation of ABCG5 which encodes an ATP-binding cassette transporter,was detected by whole exome sequencing and diagnosed as phytosterolemia.Measurement of the patient’s plasma plant sterol levels detected significant elevations in stigmasterol,rapeseed oil-derived plant sterol,andβ-glutaminol levels.Ezetimibe was started and a low plant sterol diet was recommended.The patient’s blood lipid profile was reexamined one month later and showed significant decreases in total cholesterol and LDL-C levels.Phytosterolemia has similar clinical features as familial hypercholesterolemia,is highly susceptible to misdiagnosis,and has a very low incidence,and therefore clinicians need to consider a genetic diagnosis of a definitively hyperlipidemic disorder when statin drugs fail to lower lipid levels.CONCLUSION Phytosterolemia is easily misdiagnosed as familial hypercholesterolaemia and can be treated by dietary modification and cholesterol absorption inhibitors to lower blood lipids. 展开更多
关键词 HYPERCHOLESTEROLEMIA CHOLESTEROL Low-density lipoprotein Phytosterolemia Liquid chromatography ABCG5/ABCG8 Sitosterolemia
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家蚕孤雌生殖差异脂蛋白30K lipoprotein precursor基因的克隆与生物信息学分析 被引量:4
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作者 王丹 聂作明 +6 位作者 龙晓辉 刘立丽 陈健 吕正兵 陈芳 吴祥甫 张耀洲 《蚕业科学》 CAS CSCD 北大核心 2008年第2期205-210,共6页
应用二维凝胶电泳(2-DE)技术分离家蚕孤雌生殖蚁蚕总蛋白,并和正常蚁蚕总蛋白进行比较,得到46个可能与家蚕孤雌生殖相关的差异蛋白点。对这些差异蛋白点进行胶内酶解后基质辅助激光解吸电离串联飞行时间质谱(MALDI-TOF-TOFMS)分... 应用二维凝胶电泳(2-DE)技术分离家蚕孤雌生殖蚁蚕总蛋白,并和正常蚁蚕总蛋白进行比较,得到46个可能与家蚕孤雌生殖相关的差异蛋白点。对这些差异蛋白点进行胶内酶解后基质辅助激光解吸电离串联飞行时间质谱(MALDI-TOF-TOFMS)分析,经数据库搜索鉴定,确定其中一个差异蛋白点为脂蛋白30Klipoprotein precursor(30KLPP)。通过5′-RACE技术克隆到30KLPP脂蛋白的全长cDNA序列。生物信息学分析显示该差异蛋白基因全长917bp。编码261个氨基酸,理论分子质量为30.013kD,等电点为7.193;结构域和三级结构预测显示该蛋白包含1个Lipoprotein_11结构域和12个β-折叠。预测其信号肽概率为1.000,定位在1~20aa区域,即可能存在信号肽。细胞定位预测显示该蛋白可能分泌到胞外(SP值为0.934)。分析结果有助于进一步研究30KLPP脂蛋白结构与功能的关系。 展开更多
关键词 家蚕 孤雌生殖 脂蛋白30K LPP 基质辅助激光解吸电离串联飞行时间质谱
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非常规血脂指标在2型糖尿病患者心血管风险评估中的应用进展
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作者 张晓乐 祝倩雯 +1 位作者 侯中立 米娜瓦尔·胡加艾合买提 《医学综述》 CAS 2025年第1期87-91,共5页
动脉粥样硬化性血脂异常与心血管疾病的发病率和死亡率之间的残余风险密切相关,即使2型糖尿病(T2DM)患者的低密度脂蛋白胆固醇(LDL-C)水平达标后,这种风险依然存在。非常规血脂指标[如非高密度脂蛋白胆固醇(HDL-C)、三酰甘油/HDL-C比值... 动脉粥样硬化性血脂异常与心血管疾病的发病率和死亡率之间的残余风险密切相关,即使2型糖尿病(T2DM)患者的低密度脂蛋白胆固醇(LDL-C)水平达标后,这种风险依然存在。非常规血脂指标[如非高密度脂蛋白胆固醇(HDL-C)、三酰甘油/HDL-C比值、LDL-C/HDL-C比值、总胆固醇/HDL-C比值]在T2DM患者的心血管风险预测中逐渐受到重视。心血管风险的早期识别对于优化T2DM管理至关重要。随着心血管疾病预防策略的不断细化,研究的重点逐渐转向简便、全面且有效的心血管疾病风险分层方法。未来将进一步评估上述指标与其他代谢参数的协同作用,精确区分阈值,优化个体化治疗,并通过动态监测上述指标加强精准的心血管风险管理。 展开更多
关键词 2型糖尿病 心血管风险 非高密度脂蛋白胆固醇 心血管疾病 预防
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Role of PERK/eIF2α/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis 被引量:21
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作者 TAO Yong Kang YU Pu Lin +3 位作者 BAI Yong Ping YAN Sheng Tao ZHAO Shui Ping ZHANG Guo Qiang 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2016年第12期868-876,共9页
Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in th... Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis. 展开更多
关键词 PERK elF2a CHOP Endoplasmic reticulum stress Oxidized low-density lipoprotein Endothelial cell Apoptosis ATHEROSCLEROSIS Caspase-3
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Lipoprotein(a) in type 2 diabetic subjects and its relationship to diabetic microvascular complications 被引量:13
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作者 Radhakrishnan Chandni Kollengode Parameswaran Ramamoorthy 《World Journal of Diabetes》 SCIE CAS 2012年第5期105-109,共5页
AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes mellitus patients and to determine the relationship between Lp(a) in type 2 diabetes mellitus patients and micro-vascular complications. ... AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes mellitus patients and to determine the relationship between Lp(a) in type 2 diabetes mellitus patients and micro-vascular complications. METHODS: A cross sectional study was performed that enrolled 144 subjects with type 2 diabetes mellitus above the age of 25 years attending outpatient clinic of Government Medical College, Kozhikode. Lp(a) levels were measured quantitatively in venous samples using Turbidimetric Immunoassay in all subjects. Each patient was evaluated for micro vascular complications, namely diabetic retinopathy, nephropathy and neuropathy. The relationship between Lp(a) levels and the micro vascular complications was assessed by univariate analysis. RESULTS: Mean age of cases was 53.93 ± 10.74 years with a male to female ratio of 1.3:1. Mean duration of diabetes was 9.53 ± 7.3 years. Abnormal Lp(a) levels (≥ 30 mg/dL) were observed in 38 (26.4%) diabetic subjects. Seventy-eight (54.16%) cases had diabetic nephropathy and significantly higher Lp(a) levels were found among these cases [Median 28.2 mg/dL (Interquartile range; IQR 24.4-33.5) vs 19.3 mg/dL (IQR 14.7-23.5); P < 0.05]. Retinopathy was present among 66 (45.13%) cases and peripheral neuropathy was detected among 54 (37.5%) cases. However, Lp(a) levels were not significantly different among those with or without retinopathy and neuropathy. Positive correlation was found between higher Lp(a) levels and duration of diabetes (r = 0.165, P < 0.05) but not with HbA1c values (r = - 0.083). CONCLUSION: Abnormal Lp(a) levels were found among 26.4% of diabetic subjects. Patients with diabetic nephropathy had higher Lp(a) levels. No association was found between Lp(a) levels and diabetic retinopathy or neuropathy. Longer duration of diabetes correlated with higher Lp(a) levels. 展开更多
关键词 Diabetes MELLITUS lipoprotein(a) Micro vascular complications DIABETIC NEPHROPATHY DIABETIC RETINOPATHY DIABETIC NEUROPATHY
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High-density lipoprotein and atherosclerosis: Roles of lipid transporters 被引量:10
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作者 Yoshinari Uehara Keijiro Saku 《World Journal of Cardiology》 CAS 2014年第10期1049-1059,共11页
Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-... Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases. 展开更多
关键词 ATP-BINDING CASSETTE transporter ATP-bind-ing CASSETTE A1 ATP-BINDING CASSETTE G1 Apolipopro-tein A-I HIGH-DENSITY lipoprotein HIGH-DENSITY lipopro-tein therapy APOA-I MIMETIC peptide Reconstitutedf HIGH-DENSITY lipoprotein
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Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target 被引量:10
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作者 Rocio Toro Eduardo Segura +3 位作者 Jesfis Millan Nunez-Cortes Juan Carlos Pedro-Botet Maribel Quezada-Feijoo Alipio Mangas 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2015年第2期93-99,共7页
Objectives Increased lipoprotein (a) serum concentration seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper ins... Objectives Increased lipoprotein (a) serum concentration seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. Methods This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro and macrovascular complications were collected. Results Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2± 17.3 mg/dL (22.1± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P 〈 0.01 and P 〈 0.005, respectively). Conclusions The elevation of plasma levels of lipoprotein (a) are associ- ated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus. 展开更多
关键词 lipoprotein (a) Macrovascular complications Type 2 diabetes Risk factors
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颈动脉CTA评估颈动脉粥样硬化狭窄程度及与血清脂蛋白相关磷脂酶A2、血管生成素样蛋白8水平的相关性分析
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作者 左玮玮 郭泓江 《陕西医学杂志》 CAS 2025年第1期62-66,共5页
目的:探讨颈动脉计算机断层扫描血管成像(CTA)评估颈动脉粥样硬化(CAS)狭窄程度及与血清脂蛋白相关磷脂酶A2(Lp-PLA2)、血管生成素样蛋白8(ANCPTL8)水平的相关性。方法:选取颈动脉粥样硬化合并颈动脉狭窄患者155例为合并组,根据病情严... 目的:探讨颈动脉计算机断层扫描血管成像(CTA)评估颈动脉粥样硬化(CAS)狭窄程度及与血清脂蛋白相关磷脂酶A2(Lp-PLA2)、血管生成素样蛋白8(ANCPTL8)水平的相关性。方法:选取颈动脉粥样硬化合并颈动脉狭窄患者155例为合并组,根据病情严重程度分为轻度组(n=50)、中度组(n=38)和重度组(n=67),另选92例单纯颈动脉粥样硬化患者为未合并组。比较不同病情严重程度颈动脉狭窄患者血清Lp-PLA2、ANCPTL8水平,多因素Logistic回归分析颈动脉粥样硬化患者合并颈动脉狭窄的危险因素,以数字减影血管造影(DSA)为金标准,分析CTA检测颈动脉狭窄程度的评估价值。结果:与DSA检测结果比较,CTA检测结果无统计学差异(P>0.05)。与轻度组比较,中度组和重度组患者血清Lp-PLA2、ANCPTL8水平显著升高(均P<0.05),与中度组患者比较,重度组患者血清Lp-PLA2、ANCPTL8水平显著升高(均P<0.05)。两组年龄、性别、吸烟史、高脂血症、血清高密度脂蛋白、低密度脂蛋白水平之间比较无统计学差异(均P>0.05),合并组患者高血压、糖尿病、冠心病患者占比、血清Lp-PLA2、ANCPTL8水平显著高于未合并组(均P<0.05)。高血压、糖尿病、冠心病、高血清Lp-PLA2、ANCPTL8水平是颈动脉粥样硬化患者合并颈动脉狭窄的危险因素(均P<0.05)。血清Lp-PLA2、ANCPTL8水平与患者颈动脉狭窄程度具有较高相关性,且与其呈正相关(均P<0.05)。结论:颈动脉CTA检测对颈动脉狭窄程度具有较高的评估价值,且血清Lp-PLA2、ANCPTL8水平与患者颈动脉狭窄程度具有较高相关性。高血压、糖尿病、冠心病、高血清Lp-PLA2、ANCPTL8水平是颈动脉粥样硬化患者合并颈动脉狭窄的危险因素。 展开更多
关键词 颈动脉粥样硬化 计算机断层扫描血管成像 脂蛋白相关磷脂酶A2 血管生成素样蛋白8 颈动脉狭窄 相关性
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