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中华重症医学电子杂志 ›› 2018, Vol. 04 ›› Issue (02) : 164 -169. doi: 10.3877/cma.j.issn.2096-1537.2018.02.012

所属专题: 文献

基础研究

脓毒症大鼠血清高迁移率族蛋白B1、Toll样受体4时间-浓度变化关系研究
任珊1, 张远1, 于明基1, 许航1, 陈江玲2, 尤伟艳1,()   
  1. 1. 832000 石河子大学医学院第一附属医院重症医学I科
    2. 841007 新疆生产建设兵团第二师医院重症医学科
  • 收稿日期:2017-03-04 出版日期:2018-05-28
  • 通信作者: 尤伟艳
  • 基金资助:
    石河子大学医学院第一附属医院院级科研项目(ss2014035); 石河子大学高层次人才科研启动项目(RCZX201443)

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

Shan Ren1, Yuan Zhang1, Mingji Yu1, Hang Xu1, Jiangling Chen2, Weiyan You1,()   

  1. 1. Department of Intensive Care Unit, the First Affiliated Hospital of the Medical College, Shihezi University 832000, China
    2. Department of Intensive Care Unit, the Second Division Hospital of Xinjiang Production and Construction Corps 841007, China
  • Received:2017-03-04 Published:2018-05-28
  • Corresponding author: Weiyan You
  • About author:
    Corresponding author: You Weiyan, Email:
引用本文:

任珊, 张远, 于明基, 许航, 陈江玲, 尤伟艳. 脓毒症大鼠血清高迁移率族蛋白B1、Toll样受体4时间-浓度变化关系研究[J]. 中华重症医学电子杂志, 2018, 04(02): 164-169.

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.

目的

检测不同时间点脓毒症大鼠血清高迁移率族蛋白B1(HMGB1)及Toll样受体4(TLR4)浓度,探讨脓毒症炎症反应的可能机制,寻找脓毒症早期诊断的潜在生物标志物。

方法

以盲肠结扎穿孔(CLP)法构建脓毒症大鼠模型,随机分为CLP组,HMGB1干预组,TLR4干预组,以假手术组(麻醉后开腹翻动盲肠后关腹)及空白组(不做任何处理的正常大鼠)为对照。于CLP术后2、4、8、12、24、48 h以酶联免疫吸附测定(ELISA)法检测试验动物血清HMGB1及TLR4蛋白浓度,分析其时间-浓度关系。

结果

CLP组各检测时间点血清HMGB1浓度较空白组及假手术组明显升高(P<0.05),于24 h达峰;予以HMGB1干预后,相比CLP组,其在术后4 h开始发挥作用,明显降低血清HMGB1浓度(P<0.05);予以TLR4干预,相比CLP组,其在术后2~24 h内明显降低血清HMGB1浓度(P<0.05),相比HMGB1干预组,TLR4抑制发挥作用开始时间更早(2 h,P<0.05),作用更强(12、24 h,P<0.05)。血清TLR4蛋白浓度在CLP组呈双峰表达(8、24 h,P<0.05);予以HMGB1干预,相比CLP组,其血清TLR4表达呈单峰(8 h,P<0.05);予以TLR4干预,其血清TLR4变化较为复杂,再次呈现双峰状,峰值提前且增加(4、12 h,P<0.05)。

结论

HMGB1可能通过TLR4信号通路发挥作用,脓毒症炎症级联反应、炎性细胞因子释放等信号转导通路是复杂的、相互交织的"cross-link"系统,单一改变某个/某些个信号转录调节因子作用有限。

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
图1 各组动物不同时间点血清HMGB1浓度比较
表1 各组动物不同时间点血清HMGB1浓度比较(μg/ml,±s
图2 各组动物不同时间点血清TLR4浓度比较
表2 各组动物不同时间点血清TLR4浓度比较(μg/ml,±s
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