目的 探讨血清Toll样受体4(Toll-like receptor 4,TLR4)、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)对重度烧伤患者急性肾损伤的早期诊断价值。 方法 回顾性分析2019年8月～2021年8月浙江省台州医院收治的45例重度烧伤患者临床资料，根据患者伤后1周内是否出现急性肾损伤分为急性肾损伤组(n=20)与非急性肾损伤组(n=25)。收集患者急性及慢性健康评分(acute physiology, age and chronic health evaluation II，APACHEII)、序贯器官衰竭估计评分(sepsis-related organ failure assessment，SOFA)等基本资料，采用酶联免疫吸附法检测伤后24h、48h及72d血清TLR4、HMGB1水平。应用研究对象工作特征曲线(ROC)和曲线下面积(AUC)评价血清TLR4、HMGB1对重度烧伤患者急性肾损伤的早期诊断价值，采用多因素Logistic回归分析探讨重度烧伤患者发生急性肾损伤的相关因素。 结果 急性肾损伤组SOFA评分、APACHEⅡ评分与血清Scr水平均高于非急性肾损伤组(t=16.839、4.643、7.287，均P＜0.001)。急性肾损伤组伤后24、48、72h血清TLR4[(4.12±0.36)ng/ml、(6.22±0.96)ng/ml、(8.06±1.24)ng/ml]、HMGB1[(9.63±2.28)pg/ml、(12.47±3.16)pg/ml、(15.20±3.47)pg/ml]水平均高于非急性肾损伤组[(2.33±0.25)ng/ml、(4.02±0.30)ng/ml、(6.14±1.02)ng/ml；(6.23±1.20)pg/ml、(8.64±2.36)pg/ml、(11.15±3.6)pg/ml](t=8.076、9.203、5.339、4.951、6.036、5.618，均P＜0.001)。TLR4曲线下面积、截断值、灵敏度及特异性分别为0.862、4.50ng/ml、86.5%、85.4%；HMGB1曲线下面积、截断值、灵敏度及特异性分别为0.845、6.22pg/ml、83.7%、80.6%，且TLR4、HMGB1的灵敏度与特异性均高于SOFA评分(70.8%、75.4%)、Scr(72.6%、77.0%)。SOFA评分≥4分[OR(95% CI)=2.62(1.40～4.91,P＜0.001]、Scr≥133.00μmol/L[OR(95% CI)=3.45(1.52～7.89),P＜0.001]、TLR4≥4.50ng/ml[OR(95% CI)=3.87(1.70～8.80),P＜0.001]、HMGB1≥6.22pg/ml[OR(95% CI)=4.27(2.10～8.70),P＜0.001]均为重度烧伤患者发生急性肾损伤的危险因素。 结论 重度烧伤患者血清TLR4、HMGB1水平升高，且出现急性肾损伤的重度烧伤患者血清TLR4、HMGB1水平更高，二者可用于预测重度烧伤患者急性肾损伤的发生。
Objective To investigate the value of serum Toll-like receptor 4 (TLR4) and high mobility group protein B1 (HMGB1) in the early diagnosis of acute kidney injury (AKI) in severely burned patients. Methods The clinical data of 45 patients with severe burn treated in Taizhou Hospital of Zhejiang Province from August 2019 to August 2021 were retrospectively analyzed. According to the presence or absence of AKI within one week after burn, they were divided into AKI group (n=20) and non-AKI group (n=25). Their basic data, acute physiology, age and chronic health evaluation II (APACHE II) and sequential organ failure estimation score (SOFA) were collected. Serum TLR4 and HMGB1 were detected by enzyme-linked immunosorbent assay at 24, 48 and 72 days after burn. The working characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the value of serum TLR4 and HMGB1 in the early diagnosis of AKI in severely burned patients. Multivariate logistic regression was used to explore the risk factors for the occurrence of AKI in severely burned patients. Results SOFA score, APACHE Ⅱ score and serum Scr were higher in AKI group than in non-AKI group (t=16.839, 4.643 and 7.287 respectively; P＜0.001). Comparing between AKI group and non- AKI group, serum TLR4 levels were 4.12±0.36 vs. 2.33±0.25, 6.22±0.96 vs. 4.02±0.30, and 8.06±1.24 vs. 6.14±1.02 ng/ml after severe burn for 24, 48 and 72h respectively (t=8.076, 9.203 and 5.339 respectively; P＜0.001); serum HMGB1 levels were 9.63±2.28 vs. 6.23±1.20, 12.47±3.16 vs. 8.64±2.36, and 15.20±3.47 vs. 11.15±3.6 pg/ml after severe burn for 24, 48 and 72h respectively (t=4.951, 6.036 and 5.618 respectively; P＜0.001). Serum TLR4 and HMGB1 levels reached the highest at 72 hours after severe burn. ROC analysis showed that the AUC, cut-off value, sensitivity and specificity for serum TLR4 were 0.862, 4.50 ng/ml, 86.5% and 85.4%, respectively, and those for serum HMGB1 were 0.845, 6.22 ng/ml, 83.7% and 80.6%, respectively. The sensitivity and specificity of TLR4 (86.5% and 85.4%) and HMGB1 (83.7% and 80.6%) were higher than those of SOFA score (70.8% and 75.4%) and Scr (72.6% and 77.0%). SOFA score ≥4 points [OR (95% CI)=2.62 (1.40～4.91), P＜0.001], Scr≥133.00 μmol/L [OR (95% CI)=3.45 (1.52-7.89), P＜0.001], TLR4≥4.50 ng/ml [OR (95% CI)=3.87 (1.70～8.80), P＜0.001] and HMGB1≥6.22 pg/ml [OR (95% CI)=4.27 (2.10～8.70), P＜0.001] were the risk factors for AKI in severely burned patients. Conclusion Serum TLR4 and HMGB1 levels increased in severely burned patients, and increased more in the severely burned patients with AKI. Both can predict AKI in severely burned patients. The two serum levels are expected to be used as biomarkers for the prediction of AKI in severely burned patients.
[1]Roshangar L, Soleimani Rad J, Kheirjou R, et al. Skin Burns: Review of Molecular Mechanisms and Therapeutic Approaches[J]. Wounds, 2019, 31(12):308-315.
[2]Folkestad T, Brurberg KG, Nordhuus KM, et al. Acute kidney injury in burn patients admitted to the intensive care unit: a systematic review and meta-analysis[J]. Crit Care, 2020 Jan 2;24(1):2.
[3]王曌华, 张永, 裴敬仲. 连续性肾脏替代疗法在烧伤创面脓毒症中的应用[J]. 保健医学研究与实践, 2020, 17(5): 55-58.
[4]Ciesielska A, Matyjek M, Kwiatkowska K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling[J]. Cell Mol Life Sci, 2021, 78(4):1233-1261.
[5]崔文娟,乔鲁军,牟林,等.高迁移率族蛋白B1对脓毒症及相关急性肾损伤的诊断和无价值研究[J].中国实验诊断学, 2019, 23(2):29-31.
[6]熊焱强,李会,王玎,等.高迁移率族蛋白B1与宫颈癌相关性的研究进展[J].安徽医药,2019, 23(12):2333-2336.
[7]郭锦洲.改善全球肾脏病预后组织(KDIGO)临床实践指南:急性肾损伤[J].肾脏病与透析肾移植杂志, 2013, 22(1):57-60.
[8]Tejiram S, Romanowski KS, Palmieri TL. Initial management of severe burn injury[J]. Curr Opin Crit Care, 2019, 25(6):647-652.
[9]Osuka A, Kusuki H, Matsuura H, et al. Acute intestinal damage following severe burn correlates with the development of multiple organ dysfunction syndrome: A prospective cohort study[J]. Burns, 2017, 43(4):824-829.
[10]Lam NN, Hung TD, Hung DK. Acute respiratory distress syndrome among severe burn patients in a developing country: application result of the berlin definition[J]. Ann Burns Fire Disasters, 2018, 31(1):9-12.
[11]Tsai SY, Lio CF, Shih SC, et al. The predisposing factors of AKI for prophylactic strategies in burn care[J]. Peer J, 2020, 8:e9984.
[12]王东青, 杨文, 杨林,等. sNGAL,uNGAL及uKIM-1水平在重症监护病房急性肾损伤中的应用价值[J]. 标记免疫分析与临床, 2019, 26(12):39-42.
[13]杨静, 何浩, 谭波,等. 血清TLR4,MFG-E8及HMGB1对脓毒症患者并发急性肾损伤的诊断价值[J]. 山东医药, 2020, 60(1):36-40.
[14]李文, 程帆, 魏捷,等. HMGB1调控急性肾损伤失控性炎症反应的研究进展[J]. 临床急诊杂志, 2018, 19(10):713-718.
[15]Wen Y, Han C, Liu T, et al. Chaiqin chengqi decoction alleviates severity of acute pancreatitis via inhibition of TLR4 and NLRP3 inflammasome: Identification of bioactive ingredients via pharmacological sub-network analysis and experimental validation[J]. Phytomedicine, 2020, 79:153328.
[16]叶芳丽,魏小斌,潘在兴,等. 血清sTREM-1、HMGB1用于评估重型颅脑损伤并发肺部感染的临床价值[J]. 浙江医学,2021,43(2):172-175,222.
[17] Li XP, Liu P, Li YF, et al. LPS induces activation of the TLR4 pathway in fibroblasts and promotes skin scar formation through collagen I and TGF-β in skin lesions[J]. Int J Clin Exp Pathol, 2019, 12(6):2121-2129.
[18] Liu S, Chen HZ, Xu ZD, et al. Sodium butyrate inhibits the production of HMGB1 and attenuates severe burn plus delayed resuscitation-induced intestine injury via the p38 signaling pathway[J]. Burns, 2019, 45(3):649-658.
