动脉粥样硬化相关危险因素与自身抗原ALDH4A1的关系研究  

Research on the relationship between atherosclerosis-related risk factors and autoantigen ALDH4A1

作　　者：肖韩艳 郑健[2] 王宏军 刘茜 李岩 Xiao Hanyan;Zheng Jian;Wang Hongjun;Liu Qian;Li Yan(Department of Neurology,Changzhou Fourth People's Hospital,Changzhou 213000,China;Department of Neurosurgery,Shengjing Hospital,China Medical University,Shenyang 110000,China;Department of Cardiology,Changzhou Fourth People's Hospital,Changzhou 213000,China;Department of Clinical Laboratory,Changzhou Fourth People's Hospital,Changzhou 213000,China;Department of Gastrointestinal Surgery,Changzhou Fourth People's Hospital,Changzhou 213000,China)

机构地区：[1]常州市第四人民医院神经内科,常州213000 [2]中国医科大学附属盛京医院神经外科,沈阳110000 [3]常州市第四人民医院心内科,常州213000 [4]常州市第四人民医院检验科,常州213000 [5]常州市第四人民医院胃肠外科,常州213000

出　　处：《中华血管外科杂志》2025年第1期50-58,共9页Chinese Journal of Vascular Surgery

基　　金：常州市“十四五”卫生健康高层次人才项目(2022CZBJ082)。

摘　　要：目的探讨动脉粥样硬化相关危险因素与自身抗原醛脱氢酶4家族成员A1(ALDH4A1)的关系。方法采用回顾性队列研究方法和实验研究方法。收集2023年1月至2023年3月常州市第四人民医院神经内科动脉粥样硬化患者(动脉粥样硬化组)和健康体检者(健康对照组)各40例的临床资料,并采集其血清样本。其中动脉粥样硬化组男性22例,女性18例,中位年龄66.50(61.00,72.50)岁;健康对照组男性20例,女性20例,中位年龄64.50(58.00,69.50)岁。动物实验中,空白组为野生型C57小鼠;模型组采用高脂饮食喂养APOE-/-小鼠建立动脉粥样硬化模型,应用ALDH4A1及ALDH4A1抗体干预模型组小鼠分别建立ALDH4A1组和Anti-ALDH4A1组,每组各10只。(1)应用酶联免疫吸附试验(ELISA)检测人和小鼠血清中的ALDH4A1蛋白水平;(2)油红O染色检测小鼠心脏瓣膜区动脉粥样硬化病变情况;(3)细胞实验中模拟动脉粥样硬化相关危险因素(包括高血压、高血糖、高血脂、炎症)作用于血管内皮细胞,应用流式细胞术检测细胞凋亡情况,ELISA及蛋白质印迹法检测ALDH4A1在细胞及培养基中的分布情况。正态分布的计量资料两组间比较采用独立样本t检验,多组间比较采用单因素方差分析。偏态分布的计量资料组间比较采用Wilcoxon秩和检验。计数资料组间比较采用χ^(2)检验。多因素分析采用Logistic回归模型。结果(1)动脉粥样硬化组患者血清中ALDH4A1蛋白浓度高于健康对照组,差异有统计学意义[(1.209±0.720)μmol/L比(0.649±0.285)μmol/L,t=14.580,P<0.001]。模型组小鼠血清中ALDH4A1蛋白浓度高于空白组,差异有统计学意义[(0.139±0.025)μmol/L比(0.075±0.037)μmol/L,t=19.540,P<0.001]。Logistic回归分析显示,ALDH4A1为动脉粥样硬化的独立危险因素(OR=1.267,95%CI:1.023~1.678,P=0.027),而年龄增大(OR=3.421,95%CI:1.011~1.321,P=0.034)、高血压(OR=4.105,95%CI:1.843~7.878,P=0.015)、总胆固醇升高(OR=5.336,95%CI:1.33ObjectiveTo investigate the relationship between atherosclerosis-related risk factors and autoantigen aldehyde dehydrogenase 4 family member A1(ALDH4A1).MethodsThe retrospective cohort study and experimental study were conducted.Clinical data and serum samples of 40 patients with atherosclerosis(atherosclerosis group)and 40 healthy subjects(healthy control group)from the Department of Neurology of Changzhou Fourth People's Hospital between January 2023 and March 2023 were collected.22 males and 18 females were included in the atherosclerosis group,with the median age of 66.50(61.00,72.50)years.20 males and 20 females were included in the healthy control group,with the median age was 64.50(58.00,69.50)years.In animal experiments,the blank control group was wild-type C57 mice.The atherosclerosis model group(model group)was the ApoE-/-mice fed with high-fat diets.With the intervention of ALDH4A1 and ALD4A1 antibodies,the ALDH4A1 group and the Anti-ADH4A1 group were established,each with 10 mice.(1)Enzyme-linked immunosorbent assay(ELISA)was used to detect the concentrations of ALDH4A1 in the serum of atherosclerosis cases and mouse models for atherosclerosis.(2)Oil Red O(ORO)staining was used to detect atherosclerotic lesions in the heart valve of the mice.(3)The effects of atherosclerosis-related risk factors(including hypertension,hyperglycemia,hyperlipidemia,and inflammation)on vascular endothelial cells were simulated in the cell experiments.Their apoptosis was detected by flow cytometry,and the distribution of ALDH4A1 in cells and culture media was detected by ELISA and western blotting(WB).The measurement data of normal distribution were compared between two groups using independent sample t test,and the comparison among groups using one-way analysis of variance.The Wilcoxon rank sum test was used to compare the skew distribution between data sets.Chi-square test was used to compare data groups.Logisitic regression model was used for multivariate analysis.Results(1)More ALDH4A1 was detected in the serum of the

关 键 词：动脉粥样硬化 自身抗原醛脱氢酶4家族成员A1 血管内皮细胞 

分 类 号：R54[医药卫生—心血管疾病]