肾移植受者代谢标志物与血脂水平的相关性研究  

Correlation between metabolic markers and blood lipid levels in kidney transplant recipients

作　　者：徐媛 侯霜 陈乾 牛玉林 李海洋 Xu Yuan;Hou Shuang;Chen Qian;Niu Yulin;Li Haiyang(Department of Organ Transplantation,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学附属医院器官移植科,贵阳550004 [2]贵州省器官移植中心

出　　处：《器官移植》2024年第4期599-606,共8页Organ Transplantation

基　　金：贵州省基础研究计划(自然科学类)项目(黔科合基础-ZK[2023]376);贵州省卫生健康委科学技术基金项目(gzwkj2023-164)。

摘　　要：目的分析肾移植受者血脂代谢、高脂血症、他克莫司药物代谢中共表达的基因及其与血脂水平的相关性。方法从比较毒理基因组学数据库(CTD)中筛选出共表达的基因。收集25例肾移植受者的一般资料,检测ATP结合盒亚家族A成员1(ABCA1)、过氧化物酶体增殖物激活受体γ(PPAR-γ)、糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(GPIHBP1)的表达情况。对肾移植受者进行跟踪随访,收集术后1、3、6、12个月空腹血糖、糖化血红蛋白、甘油三酯、总蛋白、白蛋白、球蛋白、胆固醇、高密度脂蛋白、低密度脂蛋白、他克莫司血药浓度,并分析受者高脂血症的发生情况。分析ABCA1、GPIHBP1、PPAR-γ与临床指标的相关性,及其与相关指标对肾移植术后高脂血症的诊断效能。结果共筛选出3个共表基因ABCA1、PPAR-γ、GPIHBP1。ABCA1与术后6个月胆固醇、术后3个月他克莫司血药浓度成正相关,与术后3个月空腹血糖呈负相关(均为P<0.05);GPIHBP1与术前胆固醇、术前甘油三酯呈负相关,与术后3个月他克莫司血药浓度呈正相关(均为P<0.05)。PPAR-γ与术前球蛋白、术前低密度脂蛋白呈负相关(均为P<0.05)。ABCA1、GPIHBP1、PPAR-γ联合术前球蛋白及术后1、6个月血糖水平诊断肾移植术后高甘油三酯血症的效果较好(AUC=0.900)。ABCA1、GPIHBP1、PPAR-γ联合术后1、6个月他克莫司血药浓度及术后6个月血糖水平诊断肾移植术后高胆固醇血症的效果较好(AUC=0.931)。结论ABCA1、GPIHBP1、PPAR-γ与肾移植术后血脂、他克莫司血药浓度等指标存在不同程度的相关关系,但用于预测肾移植术后高脂血症尚无确切依据。提升机体免疫力、规范的血糖管理可能是控制高脂血症的有益因素。Objective To analyze the co-expressed genes in blood lipid metabolism,hyperlipidemia and tacrolimus metabolism and their correlation with blood lipid levels in kidney transplant recipients.Methods Co-expressed genes were screened from Comparative Toxicogenomic Database(CTD).Baseline data of 25 kidney transplant recipients were collected.The expression levels of ATP binding cassette subfamily A member 1(ABCA1),peroxisome proliferator activated receptorγ(PPAR-γ)and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1(GPIHBP1)were measured.All recipients were followed up.The concentrations of fasting blood glucose,glycosylated hemoglobin,triglyceride,total protein,albumin,globulin,cholesterol,high-density lipoprotein,low-density lipoprotein and tacrolimus blood concentration were collected at postoperative 1,3,6 and 12 months,and the incidence of hyperlipidemia in the recipients was analyzed.The correlation between ABCA1,GPIHBP1,PPAR-γand clinical indexes was assessed.The diagnostic efficiency of related indexes for hyperlipidemia after kidney transplantation was evaluated.Results Three co-expressed genes including ABCA1,PPAR-γand GPIHBP1 were screened.ABCA1 was positively correlated with cholesterol level at postoperative 6 months and tacrolimus blood concentration at postoperative 3 months,whereas negatively correlated with fasting blood glucose level at postoperative 3 months(all P<0.05).GPIHBP1 was negatively correlated with preoperative cholesterol and triglyceride levels,whereas positively correlated with tacrolimus blood concentration at postoperative 3 months(all P<0.05).PPAR-γwas negatively correlated with preoperative globulin and low-density lipoprotein levels(both P<0.05).ABCA1,GPIHBP1 and PPAR-γcombined with preoperative globulin and blood glucose level at postoperative 1 and 6 months after operation yielded high diagnostic efficiency for hypertriglyceridemia after kidney transplantation(AUC=0.900).ABCA1,GPIHBP1 and PPAR-γcombined with tacrolimus blood concentrations a

关 键 词：肾移植 高脂血症 胆固醇 甘油三酯 他克莫司 ATP结合盒亚家族A成员1(ABCA1) 过氧化物酶体增殖物激活受体γ(PPAR-γ) 糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(GPIHBP1) 

分 类 号：R617[医药卫生—外科学] R589.2[医药卫生—临床医学]