脓毒症合并急性肾损伤患者外周血TLR4、HMGB1、MFG-E8表达水平及临床意义
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摘要
目的探讨脓毒症合并急性肾损伤患者外周血Toll受体4(TLR4)、高迁移率族蛋白box-1(HMGB1)、乳脂球表皮生长因子-8(MFG-E8)表达水平及临床意义。方法选取本院ICU收治的110例脓毒症患者,其中脓毒症合并急性肾损伤50例(SIAKI组),脓毒症不伴急性肾损伤60例(非AKI组),同时选取同期健康体检正常者50例(对照组),采用单因素方差分析3组患者TLR4、HMGB1、MFG-E8表达差异,采用Pearson分析三者表达相关性,进一步通过Logistic回归分析影响SIAKI严重程度的因素。结果 SIAKI组、非AKI组患者外周血TLR4、HMGB1表达水平明显高于对照组(P <0.05),且SIAKI组高于非AKI组(P <0.05),SIAKI组、非AKI组患者外周血MFG-E8表达水平低于对照组(P <0.05),SIAKI组低于非AKI组(P <0.05);SIAKI组患者C反应蛋白(CRP)、降钙素原(PCT)、血肌酐、尿素、尿酸及急性生理学与慢性健康情况评分系统Ⅱ(APACHEⅡ)评分显著高于非AKI组(P <0.05),肾小球滤过率(eGFR)明显低于非AKI组(P <0.05);SIAKI患者外周血TLR4、HMGB1水平与尿素、尿酸无相关性(P> 0.05),与CRP、PCT、血肌酐、eGFR、APACHEⅡ评分呈正相关(P <0.05);MFG-E8表达水平与CRP、尿素、尿酸无相关性(P>评分呈负相关(P <0.05);CRP、PCT、血肌酐、eGFR、TLR4、HMGB1是影响SIAKI严重程度的危险因素(P <0.05),MFG-E8是影响SIAKI严重程度的保护因素(P <0.05)。结论 SIAKI患者存在外周血TLR4、HMGB1水平升高,MFG-E8水平降低现象,TLR4、HMGB1、MFG-E8可作为SIAKI严重程度的检测指标。
Objective To investigate the expression levels and clinical significances of Toll receptor 4(TLR4),high mobility group protein box-1(HMGB1)and creamy globule epidermal growth factor-8(MFG-E8)in peripheral blood of patients with sepsis induced acute kidney injury. Methods 110 cases of patients with sepsis from ICU in our hospital were selected,including 50 cases of sepsis induced acute kidney injury(group SIAKI),60 cases of non-sepsis induced acute kidney injury(non AKI group),at the same time,50 healthy persons(control group)were selected. One-HMGB1 and MFG-E8 in the three groups. Pearson analysis was used to analyze the correlation of the three indica-tors.Factors affecting the severity of SIAKI were further analyzed by logistic regression. Results The expression levels of TLR4 and HMGB1 in peripheral blood of SIAKI group and non AKI group were significantly higher than thoseof the control group(P < 0.05),and SIAKI group was higher than non AKI group(P < 0.05). The expres-sion level of MFG-E8 in peripheral blood of SIAKI group and non AKI group was lower than that of control group(P < 0.05),and SIAKI group was lower than non AKI group(P < 0.05). In SIAKI group,C reactive protein(CRP),calcitonin(PTC),serum creatinine,urea,uric acid,acute physiology,and chronic health system II(APACHE II)score were significantly higher than those in non AKI group(P < 0.05),and glomerular filtration rate(eGFR)was significantly lower than that in non AKI group(P < 0.05). The levels of TLR4 and HMGB1 in peripheral blood of SIAKI patients were not correlated with urea and uric acid(P > 0.05),were significant posi-tive correlated with CRP,PCT,serum creatinine,eGFR and APACHE II score(P < 0.05). The MFG-E8 expres-sion level was not correlated with CRP,urea and uric acid(P > 0.05),was negative correlated with PCT,serum creatinine,eGFR and APACHEⅡ score(P < 0.05). CRP,PCT,serum creatinine,eGFR,TLR4 and HMGB1 were risk factors affecting the severity of SIAKI(P < 0.05). MFG-E8 was a protective factor affecting the severity of SIAKI(P < 0.05). Conclusion The levels of TLR4 and HMGB1 increased whileMFG-E8 level decreased in peripheral blood of SIAKI patients. TLR4,HMGB1 and MFG-E8 can be used as indicators of SIAKI severity.
Objective To investigate the expression levels and clinical significances of Toll receptor 4(TLR4),high mobility group protein box-1(HMGB1)and creamy globule epidermal growth factor-8(MFG-E8)in peripheral blood of patients with sepsis induced acute kidney injury. Methods 110 cases of patients with sepsis from ICU in our hospital were selected,including 50 cases of sepsis induced acute kidney injury(group SIAKI),60 cases of non-sepsis induced acute kidney injury(non AKI group),at the same time,50 healthy persons(control group)were selected. One-HMGB1 and MFG-E8 in the three groups. Pearson analysis was used to analyze the correlation of the three indica-tors.Factors affecting the severity of SIAKI were further analyzed by logistic regression. Results The expression levels of TLR4 and HMGB1 in peripheral blood of SIAKI group and non AKI group were significantly higher than thoseof the control group(P < 0.05),and SIAKI group was higher than non AKI group(P < 0.05). The expres-sion level of MFG-E8 in peripheral blood of SIAKI group and non AKI group was lower than that of control group(P < 0.05),and SIAKI group was lower than non AKI group(P < 0.05). In SIAKI group,C reactive protein(CRP),calcitonin(PTC),serum creatinine,urea,uric acid,acute physiology,and chronic health system II(APACHE II)score were significantly higher than those in non AKI group(P < 0.05),and glomerular filtration rate(eGFR)was significantly lower than that in non AKI group(P < 0.05). The levels of TLR4 and HMGB1 in peripheral blood of SIAKI patients were not correlated with urea and uric acid(P > 0.05),were significant posi-tive correlated with CRP,PCT,serum creatinine,eGFR and APACHE II score(P < 0.05). The MFG-E8 expres-sion level was not correlated with CRP,urea and uric acid(P > 0.05),was negative correlated with PCT,serum creatinine,eGFR and APACHEⅡ score(P < 0.05). CRP,PCT,serum creatinine,eGFR,TLR4 and HMGB1 were risk factors affecting the severity of SIAKI(P < 0.05). MFG-E8 was a protective factor affecting the severity of SIAKI(P < 0.05). Conclusion The levels of TLR4 and HMGB1 increased whileMFG-E8 level decreased in peripheral blood of SIAKI patients. TLR4,HMGB1 and MFG-E8 can be used as indicators of SIAKI severity.
引文
[1]ZARBOCK A,GOMEZ H,KELLUM J A.Sepsis-induced acute kidney injury revisited:pathophysiology,prevention and future therapies[J].Curr Opin Crit Care,2015,20(6):588-595.
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[8]齐明禄,杨敬平.TOLL样受体基因多态性与脓毒症的相关性研究进展[J].临床肺科杂志,2015,19(1):146-147.
[9]马兴龙,姜阳,李佳芯,等.脓毒症患者外周血TNF-α、HMGB-1、TF和vWF动态变化及临床意义[J].实用医学杂志,2018,34(4):630-633.
[10]SUN J,SHI S,WANG Q,et al.Continuous hemodiafiltration therapy reduces damage of multi-organs by ameliorating of HMGB1/TLR4/NFκB in a dog sepsis model[J].Int J Clin Exp Pathol,2015,8(2):1555-1564.
[11]安曙光,覃炳军,卢广轩,等.脓毒症患者血清高迁移率族蛋白B1对调节性T细胞免疫功能的影响[J].实用医学杂志,2018,34(17):2912-2915.
[12]AZIZ M,WANG P.MFG-E8 and acute lung injury[M].MFG-E8 and Inflammation.Springer Netherlands,2014,94(17):149-172.
[13]UMBRO I,GENTILE G,TINTI F,et al.Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury[J].J Infect,2016,72(2):131-142.
[2]符秋红.脓毒症心肌抑制对脓毒性休克患者血流动力学和器官功能及预后的影响研究[J].中国急救医学,2017,37(z1):216-217.
[3]ZHENG S,PAN Y,WANG C,et al.HMGB1 turns renal tubular epithelial cells into inflammatory promoters by interacting with TLR4 during sepsis[J].J Interferon Cytokine Res,2016,36(1):9-19.
[4]WANG X,BU H F,ZHONG W,et al.MFG-E8 and HMGB1are involved in the mechanism underlying alcohol-induced impairment of macrophage efferocytosis[J].Mol Med,2013,19(1):170-182.
[5]LEVY M M,FINK M P,MARSHALL J C,et al.2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference[J].Crit Care Med,2003,31(4):1250-1256.
[6]Kidney Disease:Improving Global Outcomes(KDIGO)Acute Kidney Injury Work Group.KDIGO clinical practice guideline for acute kidney injury[J].Kidney Inter,2012,2(suppl):1-138.
[7]MENG L,LV Z,YU Z Z,et al.Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression[J].Genet Mol Res,2016,15(3):1-8.
[8]齐明禄,杨敬平.TOLL样受体基因多态性与脓毒症的相关性研究进展[J].临床肺科杂志,2015,19(1):146-147.
[9]马兴龙,姜阳,李佳芯,等.脓毒症患者外周血TNF-α、HMGB-1、TF和vWF动态变化及临床意义[J].实用医学杂志,2018,34(4):630-633.
[10]SUN J,SHI S,WANG Q,et al.Continuous hemodiafiltration therapy reduces damage of multi-organs by ameliorating of HMGB1/TLR4/NFκB in a dog sepsis model[J].Int J Clin Exp Pathol,2015,8(2):1555-1564.
[11]安曙光,覃炳军,卢广轩,等.脓毒症患者血清高迁移率族蛋白B1对调节性T细胞免疫功能的影响[J].实用医学杂志,2018,34(17):2912-2915.
[12]AZIZ M,WANG P.MFG-E8 and acute lung injury[M].MFG-E8 and Inflammation.Springer Netherlands,2014,94(17):149-172.
[13]UMBRO I,GENTILE G,TINTI F,et al.Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury[J].J Infect,2016,72(2):131-142.