糖尿病肾病维持性血液透析患者转化生长因子-β1/p38丝裂素活化蛋白激酶通路与动静脉内瘘失功的相关性研究  

Study on the correlation between TGF-β1/p38 MAPK pathway and arteriovenous fistula dysfunction in diabetic nephropathy patients on maintenance hemodialysis

作　　者：王宇夫 彭红英 WANG Yu-fu;PENG Hong-ying(Department of Nephrology,The Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;Department of Nephrology,Baiyun Hospital,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]贵州医科大学附属医院肾内科,贵阳550004 [2]贵州医科大学附属白云医院肾内科,贵阳550025

出　　处：《中国血液净化》2025年第1期66-70,共5页Chinese Journal of Blood Purification

基　　金：贵州省贵阳市白云区科技计划项目([2019]42号)。

摘　　要：目的探讨糖尿病肾病(diabetic nephropathy,DN)维持性血液透析(maintenance hemodi-alysis,MHD)患者转化生长因子(transforming growth factor,TGF)-β1/p38丝裂素活化蛋白激酶(mitogen-activated protein kinase,MAPK)通路与动静脉内瘘(arteriovenous fistulas,AVF)失功的相关性。方法回顾性选取2019年6月—2021年6月贵州医科大学附属医院接受AVF手术并行MHD的DN患者为DN组,同期选取非DN的MHD患者为对照1组,非DN的2型糖尿病患者为对照2组。比较3组TGF-β1 mRNA、p38MAPK mRNA水平,Logistic回归分析DN MHD患者AVF失功的影响因素,ROC曲线分析TGF-β1 mRNA、p38MAPK mRNA对AVF失功的预测价值,并比较不同程度主动脉弓钙化患者TGF-β1 mRNA、p38MAPK mRNA水平。结果DN组(n=96)TGF-β1 mRNA水平高于对照1组(n=45)、对照2组(n=42)(t1=7.133,P1<0.001;t2=9.929,P2<0.001);DN组p38MAPK mRNA水平高于对照1组、对照2组(t1=5.983,P1<0.001;t2=8.046,P2<0.001)。Logistic回归分析显示主动脉弓钙化(OR=5.020,95%CI:2.996~8.413,P<0.001)、高水平校正血钙(OR=5.080,95%CI:3.026~8.527,P<0.001)、血磷(OR=3.523,95%CI:2.089~5.943,P<0.001)、TGF-β1 mRNA(OR=5.371,95%CI:3.197~9.025,P<0.001)、p38MAPK mRNA(OR=5.636,95%CI:3.339~9.513,P<0.001)为DN MHD患者AVF失功的危险因素。不同程度主动脉弓钙化患者(分为0级、1级、2级、3级)TGF-β1 mRNA比较:0级<1级<2级<3级(0级与1级比较:t1=2.219,P1=0.033;1级与2级比较:t2=2.650,P2=0.011;2级与3级比较:t3=2.523,P3=0.015),p38MAPK mRNA比较:0级<1级<2级<3级(0级与1级比较:t1=2.530,P1<0.001;1级与2级比较:t2=2.066,P2=0.045;2级与3级比较:t3=2.203,P3=0.032)。ROC曲线显示TGF-β1 mRNA、p38MAPK mRNA联合预测DN MHD患者AVF失功的AUC为0.820(95%CI:0.732~0.907),敏感度为80.65%,特异度为76.40%。结论主动脉弓钙化及TGF-β1/p38MAPK通路激活是DN MHD患者AVF失功的独立危险因素,TGF-β1/p38MAPK通路激活可能通过促进主动脉弓钙化诱导AVF失功,TGF-β1、p38MAPK水平对AVF失功具有良好的预Objective To study the correlation between TGF-β1/p38 MAPK pathway and arteriovenous fistulas(AVF)dysfunction in diabetic nephropathy(DN)patients on maintenance hemodialysis(MHD).Methods The DN patients undergoing AVF construction surgery and MHD in the Affiliated Hospital of Gui-zhou Medical University from June 2019 to June 2021 were retrospectively analyzed and defined as DN group.The non-diabetic nephropathy patients on MHD were recruited as control 1 group.The non-DN pa-tients with type 2 diabetes were recruited as control 2 group.The levels of TGF-β1 mRNA and p38 MAPK mRNA were compared among the three groups.Logistic regression was used to identify the influencing fac-tors for AVF dysfunction in DN group.ROC curve was used to evaluate the predictive value of TGF-β1 mRNA and p38 MAPK mRNA for AVF dysfunction.The levels of TGF-β1 and p38 MAPK mRNA were compared in patients with different degrees of aortic arch calcification.Results The level of TGF-β1 mRNA was higher in DN group(n=96)than in control 1 group(n=45;t=7.133,P<0.001)and control 2 group(n=42;t=9.929,P<0.001).The level of p38 MAPK mRNA was also higher in DN group(n=96)than in control 1 group(n=96;t=5.983,P<0.001)and control 2 group(n=42;t=8.046,P<0.001).Logistic regression showed that aortic arch calcification(OR=5.020,95%CI:2.996~8.413,P<0.001),higher levels of corrected blood calcium(OR=5.080,95%CI:3.026~8.527,P<0.001),blood phosphorus(OR=3.523,95%CI:2.089~5.943,P<0.001),TGF-β1 mRNA(OR=5.371,95%CI:3.197~9.025,P<0.001),and p38 MAPK mRNA(OR=5.636,95%CI:3.339~9.513,P<0.001)were the risk factors for AVF dysfunction in DN group.The degree of aortic arch calcification can be classified as grade 0,grade 1,grade 2 and grade 3.The order of TGF-β1 mRNA level was grade 0<grade 1<grade 2<grade 3(grade 0/grade 1:t=2.219,P=0.033;grade 1/grade 2:t=2.650,P=0.011;grade 2/grade 3:t=2.523,P=0.015).The order of p38 MAPK mRNA level was also grade 0<grade 1<grade 2<grade 3(grade 0/grade 1:t=2.530,P<0.001;grade 1/grade 2:t=2.066,P=0.045;grade 2/grade 3:t=2.203,P

关 键 词：糖尿病肾病 维持性血液透析 动静脉内瘘失功 主动脉弓钙化 转化生长因子-β1/p38丝裂素活化蛋白激酶通路 

分 类 号：R318.16[医药卫生—生物医学工程]