The time related concentration of serum HMGB1 and TLR4 in CLP rat model

doi:10.3877/cma.j.issn.2096-1537.2018.02.012

Abstract

Abstract:

Objective

To explore the mechanism of inflammatory response in sepsis and look for potential biomarkers for early diagnosis and treatment of sepsis, we examine the time related concentration of serum HMGB1 and TLR4 in CLP rat model.

Methods

A septic rat model was built with cecal ligation and puncture. The rats were randomized into three groups: CLP group, CLP with HMGB1 inhibitor group (HMGB1 group) and CLP with TLR4 inhibitor group (TLR4 group), control group and sham operation group (sham group). At 2, 4, 8, 12, 24, 48 h after operation/sham operation, serum HMGB1 and TLR4 concentration were examined with ELISA.

Results

Serum HMGB1 increased significantly than that in sham group and control group, peaking at 24 h (P<0.05); compared with CLP group, in HMGB1 group, HMGB1 inhibitor started to inhibit HMGB1 at 4 hours after operation significantly (P<0.05); compared with CLP group, in TLR4 group, TLR4 inhibitor decreased serum HMGB1 concentration significantly from 2 to 24 hours after operation (P<0.05); compared with HMGB1 inhibitor, TLR4 inhibitor worked earlier (at 2h after operation, P<0.05) and stronger (at 12 h and 24 h after operation, P<0.05). Serum TLR4 concentration showed a biphasic expression in CLP group (at 8 h and 24 h after operation, P<0.05); compared with CLP group, serum TLR4 concentration became monophasic with peaking at 8 h after operation when treated with HMGB1 (P<0.05); however, with TLR4 inhibitor treatment, the expression of serum TLR4 still appeared a biphasic expression, but peaking earlier and had a higher peak (peaking at 4 h and 12 h after operation, P<0.05).

Conclusion

HMGB1 can play a role in the inflammatory response of sepsis through TLR4 signal pathway. Inflammatory response of sepsis is a complex, ″cross-link″ system, which means only changing/influencing certain ″key-signal transcriptional regulation factor″ would be with limited effect.

Key words: Sepsis, HMGB1, TLR4

Shan Ren, Yuan Zhang, Mingji Yu, Hang Xu, Jiangling Chen, Weiyan You. The time related concentration of serum HMGB1 and TLR4 in CLP rat model[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2018, 04(02): 164-169.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2018.02.012

https://icu.cma-cmc.com.cn/EN/Y2018/V04/I02/164

Figures/Tables 4

References 26

[1]	崔书章, 寿松涛, 柴艳芬. 实用危重病医学[M]. 天津: 天津科学技术出版社, 2001: 913-920.
[2]	Moss M,Martin GS. A global perspective on the epidemiology of sepsis [J]. Intensive Care Med, 2004, 30(4): 527-529.
[3]	王秋卉,王锦权.脓毒症与肝细胞线粒体损伤[J].中国急救医学, 2007, 27(6): 561-563.
[4]	Slade E,Tamber PS,Vincent JL. The Surviving Sepsis Campaign: raising awareness to reduce mortality [J]. Crit Care, 2003, 7(1): 1-2.
[5]	van der Poll T,Opal SM. Host-pathogen interactions in sepsis [J]. Lancet Infect Dis, 2008, 8: 32-43.
[6]	Bone RC. Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS) [J]. Ann Intern Med, 1996, 125(8): 680-687.
[7]	Hotchkiss RS,Coopersmith CM,McDunn JE, et al. The sepsis see saw: tilting toward immunosuppression [J]. Nat Med, 2009, 15(5): 496-497.
[8]	Wiersinga WJ. Current insights in sepsis: from pathogenesis to new treatment targets [J]. Curr Opin Crit Care, 2011, 17(5): 480-486.
[9]	Słotwiński R,Słotwińska S,Kędziora S, et al. Innate immunity signaling pathways: links between immunonutrition and responses to sepsis [J]. Arch Immunol Ther Exp (Warsz), 2011, 59(2): 139-150.
[10]	Knapp S. Update on the role of Toll-like receptors during bacterial infections and sepsis [J]. Wien Med Wochenschr, 2010, 160(5-6): 107-111.
[11]	Salomao R,Brunialti MK,Rapozo MM, et al. Bacterial sensing, cell signaling, and modulation of the immune response during sepsis [J]. Shock, 2012, 38(3): 227-242.
[12]	Lee CC,Avalos AM,Ploegh HL. Accessory molecules for Toll-like receptors and their function [J]. Nat Rev Immunol, 2012, 12(3): 168-179.
[13]	Yang H,Wang H,Czura CJ, et al. The cytokine activity of HMGB1 [J]. J Leukoc Biol, 2005, 78(1): 1-8.
[14]	Zhang CC,Krieg S,Shapiro DJ. HMG-1 stimulates estrogen response element binding by estrogen receptor from stably transfected HeLa cells [J]. Mol Endocrinol, 1999, 13(4): 632-643.
[15]	Wang H,Bloom O,Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice [J]. Science, 1999, 285(5425): 248-251.
[16]	Tracey KJ,Cerami A. Tumor necrosis factor in the malnutrition (cachexia) of infection and cancer [J]. Am J Trop Med Hyg, 1992, 47(1 Pt 2): 2-7.
[17]	Yang H,Ochani M,Li J, et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1 [J]. Proc Natl Acad Sci USA, 2004, 101(1): 296-301.
[18]	Treutiger CJ,Mullins GE,Johansson AS, et al. High mobility group 1 B-box mediates activation of human endothelium [J]. J Intern Med, 2003, 254(4): 375-385.
[19]	Sunden-Cullberg J,Norrby-Teglund A,Rouhiainen A, et al. Pers mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock [J]. Crit Care Med, 2005, 33(3): 564-573.
[20]	Chen G,Li J,Ochani M, et al. Bacterial endotoxin stimulates macrophages to release HMGB1 partly through CD14- and TNF-dependent mechanisms [J]. J Leukoc Biol, 2004, 76(5): 994-1001.
[21]	Gibot S,Massin F,Cravoisy A, et al. High-mobility group box 1 protein plasma concentrations during septic shock [J]. Intensive Care Med, 2007, 33(8): 1347-1353.
[22]	Singh A,Boden G,Rao AK. Tissue factor and Toll-like receptor (TLR) 4 in hyperglycaemia-hyperinsulinaemia. Effects in healthy subjects, and type 1 and type 2 diabetes mellitus [J]. Thromb Haemost, 2015, 113(4): 750-758.
[23]	李雨泽,刘玉琴,陈向丽, 等. 2型糖尿病并发肺结核患者血清中炎症细胞因子水平变化的研究[J]. 中国防痨杂志, 2017, 39(2): 145-148.
[24]	Akira S,Takeda K. Toll-like receptor signalling [J]. Nat Rev Immunol, 2004, 4(7): 499-511.
[25]	Bruserud O. Bidirectional crosstalk between platelets and monocytes initiated by Toll-like receptor: an important step in the early defense against fungal infections? [J]. Platelets, 2013, 24(2): 85-97.
[26]	Kolek MJ,Carlquist JF,Muhlestein JB, et al. Toll-like receptor 4 gene Asp299Gly polymorphism is associated with reductions in vascular inflammation, angiographic coronary artery disease, and clinical diabetes [J]. Am Heart J, 2004, 148(6): 1034-1040.

组别	2 h	4 h	8 h	12 h	24 h	48 h
空白组	875.61	875.61	875.61	875.61	875.61	875.61
假手术组	820.99±54.63	788.43±87.18	930.77±121.93	838.04±37.57	1137.35±190.57	817.17±42.91
CLP组	1114.96±130.36^a	1152.34±109.41^a	1276.07±62.90^a	1741.37±11.73^a	1943.65±18.10^a	1088.09±125.08^a
HMGB1干预组	1274.36±375.78^a	890.25±31.01^b	801.66±137.97^b	1104.66±43.03^ab	869.4±183.30^b	802.82±110.53^b
TLR4干预组	807.77±158.43^bc	970.59±286.56^b	865.09±128.40^b	916.08±4.53^bc	575.51±26.03^abc	903.71±199.02

组别	2 h	4 h	8 h	12 h	24 h	48 h
空白组	875.61	875.61	875.61	875.61	875.61	875.61
假手术组	820.99±54.63	788.43±87.18	930.77±121.93	838.04±37.57	1137.35±190.57	817.17±42.91
CLP组	1114.96±130.36^a	1152.34±109.41^a	1276.07±62.90^a	1741.37±11.73^a	1943.65±18.10^a	1088.09±125.08^a
HMGB1干预组	1274.36±375.78^a	890.25±31.01^b	801.66±137.97^b	1104.66±43.03^ab	869.4±183.30^b	802.82±110.53^b
TLR4干预组	807.77±158.43^bc	970.59±286.56^b	865.09±128.40^b	916.08±4.53^bc	575.51±26.03^abc	903.71±199.02

组别	2 h	4 h	8 h	12 h	24 h	48 h
空白组	0.05	0.07	0.06	0.07	0.05	0.06
假手术组	0.13±0.02	0.06±0.01	0.14±0.02	0.08±0.01	0.04±0.01	0.09±0.01
CLP组	0.72±0.47^a	1.29±0.22^a	2.6±0.24^a	1.32±0.17^a	2.98±0.89^a	0.14±0.14^a
HMGB1干预组	1.19±0.16^a	1.26±0.31^a	7.84±0.68^ab	0.91±0.15^ab	0.6±0.32^ab	0.37±0.04^ab
TLR4干预组	0.93±0.08^ac	3.13±0.34^abc	0.34±0.16^abc	7.46±0.51^abc	0.73±0.04^abc	0.14±0.14^a

组别	2 h	4 h	8 h	12 h	24 h	48 h
空白组	0.05	0.07	0.06	0.07	0.05	0.06
假手术组	0.13±0.02	0.06±0.01	0.14±0.02	0.08±0.01	0.04±0.01	0.09±0.01
CLP组	0.72±0.47^a	1.29±0.22^a	2.6±0.24^a	1.32±0.17^a	2.98±0.89^a	0.14±0.14^a
HMGB1干预组	1.19±0.16^a	1.26±0.31^a	7.84±0.68^ab	0.91±0.15^ab	0.6±0.32^ab	0.37±0.04^ab
TLR4干预组	0.93±0.08^ac	3.13±0.34^abc	0.34±0.16^abc	7.46±0.51^abc	0.73±0.04^abc	0.14±0.14^a

Please choose a citation manager

Content to export