目的:观察原发性高血压早期肾损伤患者血清高迁移率蛋白B1(HMGB1)水平改变以及其水平与早期肾损伤的相关性。方法:选择2020年10月至2022年10月在衡水市人民医院门诊就诊的原发性高血压患者210例,根据尿微量白蛋白/尿肌酐值(UACR)分为早期肾损伤组(UACR 30~300 mg·g-1,92例)和对照组(UACR<30 mg·g-1,118例)。比较两组患者血清HMGB1、白细胞介素-6(IL-6)、和肿瘤坏死因子-α(TNF-α)水平改变。观察血清HMGB1水平与IL-6、TNF-α水平相关性。多因素Logistic回归分析影响原发性高血压早期肾损伤发生的相关因素。应用受试者工作特征(ROC)曲线选取血清HMGB1诊断原发性高血压早期肾损伤的最佳截断值,计算其敏感性、特异性。结果:早期肾损伤组血清HMGB1、IL-6水平高于对照组[(10.44±3.62)vs(6.87±1.89) ng·mL-1,(47.08±15.19)vs(31.25±6.09) pg·mL-1,均P<0.01],血清TNF-α水平两组之间差异无统计学意义[(28.88±8.14)vs(27.79±9.15) pg·mL-1,P>0.05]。早期肾损伤组血清HMGB1水平与IL-6水平具有相关性(r=0.650,P<0.01),与TNF-α水平相关性不显著(r=0.078,P>0.05)。多元Logistic回归分析显示,血清HMGB1、IL-6水平升高是原发性高血压早期肾损伤发生的危险因素(P<0.01)。HMGB1诊断原发性高血压早期肾损伤的最佳截断值为5.87 ng·mL-1,曲线下面积0.901(95%CI:0.854~0.947),其敏感性为98.7%,特异性65.9%。结论:原发性高血压早期肾损伤患者血清HMGB1水平升高,其水平超过5.87 ng·mL-1对原发性高血压早期肾损伤有一定预测价值,HMGB1可能通过炎症反应影响早期肾损伤的发生。 |
[1] 中国高血压防治指南修订委员会,高血压联盟(中国).中国高血压防治指南(2018年修订版)[J].中国心血管杂志,2019,24(1):1-46.
[2] WANG F,YANG C,LONG J,et al.Executive summary for the 2015 annual data report of the China kidney disease network(CK-NET)[J].Kidney Int,2019,95(3):501-505.
[3] ZHANG Z L,ZHAO L,ZHOU X Y,et al.Role of inflammation,immunity,and oxidative stress in hypertension:New insights and potential therapeutic targets[J].Front Immunol,2023,13:1098725.
[4] KIKUCHI K,TANCHAROEN S,ITO T,et al.Potential of the angiotensin receptor blockers(ARBs) telmisartan,irbesartan,and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke[J].Int J Mol Sci,2013,14(9):18899-18924.
[5] CURRAN C S,KOPP J B.RAGE pathway activation and function in chronic kidney disease and COVID-19[J].Front Med(Lausanne),2022,9:970423.
[6] HASHMAT S,RUDEMILLER N,LUND H,et al.Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats[J].Am J Physiol Renal Physiol,2016,311(3):F555-F561.
[7] O'LEARY R,PENROSE H,MIYATA K,et al.Macrophage-derived IL-6 contributes to ANG II-mediated angiotensinogen stimulation in renal proximal tubular cells[J].Am J Physiol Renal Physiol,2016,310(10):F1000-F1007.
[8] WEN Y,CROWLEY S D.Renal effects of cytokines in hypertension[J].Adv Exp Med Biol,2019,1165:443-454.
[9] DE MIGUEL C,PELEGRÍN P,BAROJA-MAZO A,et al.Emerging role of the inflammasome and pyroptosis in hypertension[J].Int J Mol Sci,2021,22(3):1064.
[10] YUAN Q,TANG B,ZHANG C,et al.Signaling pathways of chronic kidney diseases,implications for therapeutics[J].Signal Transduct Target Ther,2022,7(1):182.
[11] LV W S,BOOZ G W,WANG Y G.et al.Inflammation and renal fibrosis:recent developments on key signaling molecules as potential therapeutic targets[J].Eur J Pharmacol,2018,820:65-76.
[12] MOHAMED R,RAFIKOVA O,O'CONNOR P M,et al.Greater high-mobility group box 1 in male compared with female spontaneously hypertensive rats worsens renal ischemia-reperfusion injury[J].Clin Sci(Lond),2020,134(13):1751-1762.
[13] RIZZONI D,DE CIUCEIS C,SZCZEPANIAK P,et al.Immune system and microvascular remodeling in humans[J].Hypertension,2022,79(4):691-705.
[14] LEELAHAVANICHKUL A,SOMPARN P,ISSARA-AMPHORN J,et al.Serum neutrophil gelatinase associated lipocal in outperforms serum creatinine in detecting sepsis-induced acute kidney injury,experiments on bilateral nephrectomy and bilateral ureter obstruction mouse models[J].Shock,2016,45(5):570-576.
[15] WANG S,CAI S J,ZHANG W T,et al.High-mobility group box 1 protein antagonizes the immunosuppressive capacity and therapeutic effect of mesenchymal stem cells in acute kidney injury[J].J Transl Med,2020,18(1):175.
[16] BISCETTI F,RANDO M M,NARDELLA E,et al.High mobility group box-1 and diabetes mellitus complications:state of the art and future perspectives[J].Int J Mol Sci,2019,20(24):6258.
[17] PARK H S,KIM E N,KIM M Y,et al.The protective effect of neutralizing high-mobility group box1 against chronic cyclosporine nephrotoxicity in mice[J].Transpl Immunol,2016,34:42-49.
[18] ZHANG Y Z,ZHAO Y,WEI C L,et al.Association of common medical comorbidities with early renal damage in the Chinese tropics with essential hypertension[J].BMC Nephrol,2021,22(1):366.
[19] WILLIAMS B,MANCIA G,SPIERING W,et al.2018 ESC/ESH guidelines for the management of arterial hypertension[J].Eur Heart J,2018,39(33):3021-3104.
[20] WANG Y,ZHONG J,ZHANG X,et al.The role of HMGB1 in the pathogenesis of type 2 diabetes[J].J Diabetes Res,2016,2016:2543268. |