糖尿病肾病患者血清HMGB1和TNF-α水平与心功能的相关性研究

Correlation between the levels of serum HMGB1 and TNF-α and cardiac function in patients with diabetic kidney disease

摘要:

目的： 探讨糖尿病肾病（diabetic kidney disease，DKD）患者血清高迁移率族蛋白B1（high-mobility group box-1，HMGB1）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平与心功能的关系。方法： 收集2019年6月至2020年6月在南京医科大学附属淮安第一医院内分泌科住院的DKD患者122例（DKD组）为研究对象，根据尿蛋白-肌酐比值将研究对象分为微量蛋白尿组58例、大量蛋白尿组42例和肾功能损害组22例。选择同期体检的健康人群106例为健康对照组。检测所有受试者空腹血糖、血脂、肾功能（尿素氮和肌酐）水平和尿蛋白-肌酐比值。酶联免疫吸附法（enzyme linked immunosorbent assay，ELISA）检测血清HMGB1和TNF-α水平。采用超声心动图测量左室射血分数（left ventricular ejection fraction，LVEF）、左室舒张末径（left ventricular end-diastolic dimension，LVEDD）和左室收缩末径（left ventricular end-systolic dimension，LVESD）。组间比较采用方差分析。应用Pearson相关性检验分析DKD患者血清HMGB1和TNF-α水平与心功能的关系；logistic多元线性回归分析DKD患者心功能的影响因素。结果： ①DKD组患者空腹血糖、低密度脂蛋白胆固醇、尿素氮、肌酐和尿蛋白-肌酐比值均明显高于健康对照组（均P<0.05），而血清高密度脂蛋白胆固醇水平与健康对照组相比明显降低（P<0.05）。②HMGB1、TNF-α、LVEDD和LVESD随DKD病情进展逐渐升高，而LVEF随病情进展逐渐下降。③DKD组患者血清HMGB1和TNF-α含量与LVEF均呈负相关，与LVEDD、LVESD均呈明显正相关（均P<0.05）。④Logistic多元线性回归显示，HMGB1对DKD患者心功能影响最大，HMGB1每增加1 mmol/L，LVEF下降0.298%、LVEDD增加0.324 mm、LVESD增加0.318 mm。结论： HMGB1和TNF-α均随DKD病情进展上升，而HMGB1对DKD患者心功能影响最大。HMGB1可能在DKD患者心血管事件的发生发展中发挥重要作用，及早检测HMGB1有利于减少DKD患者心血管并发症的发生。

Abstract:

Objective: To explore the correlation between the levels of serum high-mobility group box-1（HMGB1） protein and tumor necrosis factor-α（TNF-α） and the cardiac function in patients with diabetic kidney disease（DKD）. Methods: A total of 122 DKD patients（DKD group） hospitalized in the Department of Endocrinology, The Affiliated Huai'an No.1 People’s Hospital of Nanjing Medical University between June 2019 to June 2020 were randomly selected into this study. According to the urinary protein-creatinine ratio，the subjects were divided into 58 cases in the microalbuminuria group，42 cases in the macroalbuminuria group，and 22 cases in the renal impairment group. Meanwhile，106 healthy people examined during the same period were collected as a healthy control group. The levels of fasting blood glucose，blood lipids and kidney function（urea nitrogen and creatinine） and urinary protein-creatinine ratio were detected in all subjects. Serum HMGB1 and TNF-α levels were detected by enzyme-linked immunosorbent assay（ELISA）. The left ventricular ejection fraction（LVEF），left ventricular end-diastolic dimension（LVEDD） and left ventricular end-systolic dimension（LVESD） were measured by echocardiography. Analysis of variance was used for comparison between groups. Pearson correlation test was used to analyze the correlation between serum HMGB1 and TNF-α levels and the cardiac function of patients with DKD. Logistic multiple linear regression was used to analyze the influencing factors of cardiac function in patients with DKD. Results: ①The fasting blood glucose，LDL-C，urea nitrogen，creatinine，and UALB/Cr ratio of the DKD group were significantly higher than those of the healthy control group（all P<0.05），while the HDL-C level was lower compared to the healthy control group（P<0.05）. ②HMGB1，TNF-α，LVEDD，and LVESD gradually increased with the progression of DKD，while the LVEF gradually decreased with the progression of the disease. ③Serum HMGB1 and TNF-α levels in the DKD group were negatively correlated with LVEF，and significantly positively correlated with LVEDD and LVESD（all P<0.05）. ④Logistic multiple linear regression showed that HMGB1 had the greatest impact on the cardiac function of patients with DKD. For every increase of 1 mmol/L in HMGB1，LVEF decreased by 0.298%，LVEDD increased by 0.324 mm，and LVESD increased by 0.318 mm. Conclusion: Both HMGB1 and TNF-α increase with the progression of DKD，and HMGB1 has the greatest impact on the cardiac function of patients with DKD. HMGB1 may play an important role in the occurrence and development of cardiovascular events in patients with DKD. Early detection of HMGB1 can help reduce the occurrence of cardiovascular complications in patients with DKD.