Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats  

作　　者：Yan Ma Xiang-you Yu Yi Wang 

机构地区：[1]Department of Intensive Care Unit, the First Affiliated Hospital, Xinjiang Medical University

出　　处：《World Journal of Emergency Medicine》2018年第1期56-63,共8页世界急诊医学杂志（英文）

基　　金：supported by grants from NSFC(National Natural Science Foundation of China,grant number81160232);CMA(Chinese Medical Association Intensive Scientific Research Fund project,grant number 13091520537);the First Affiliated Hospital of Xinjiang Medical University Natural Science Fund project(grant number 2013ZRQN11)

摘　　要：BACKGROUND: Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a controlled experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture(CLP) model in rats. METHODS: After CLP, 48 Wistar rats were randomly allocated into four groups:(1) CLP group;(2) small-dose treatment group(2.5 g·kg^(-1)·h^(-1));(3) medium-dose treatment group(5.0 g·kg^(-1)·h^(-1)); and(4) large-dose treatment group(10.0 g·kg^(-1)·h^(-1)). HLA-DR and plasma cytokine(IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure(MAP), heart rate(HR), arterial blood gases, lactate concentrations and mortality were also documented. RESULTS: The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups(DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels(P_(group)=0.0202) and increased IL-6 production, which was increased at 3 h(P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR(P<0.001) while maintaining MAP(P_(group)=0.1238), and remarkably improving lactate(P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively.CONCLUSION: Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dosedependently.BACKGROUND： Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a controlled experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture （CLP） model in rats. METHODS： After CLP, 48 Wistar rats were randomly allocated into four groups： （1） CLP group; （2） small-dose treatment group （2.5 μg.kg-1.h-1）; （3） medium-dose treatment group （5.0 μg.kg-1. h-1）; and （4） large-dose treatment group （10.0 μg.kg-1.h-1）. HLA-DR and plasma cytokine （IL-4, IL-6, IL-10 and TNF-α） levels were measured, and the mean arterial blood pressure （MAP）, heart rate （HR）, arterial blood gases, lactate concentrations and mortality were also documented. RESULTS： The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups （DEX groups）. Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels （Pgroup=0.0202） and increased IL-6 production, which was increased at 3 h （P=- 0.0113） and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR （P〈0.001） while maintaining MAP （Pgroup=0.1238）, and remarkably improving lactate （P〈0.0001）. All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively. CONCLUSION： Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dose- dependently.

关 键 词：DEXMEDETOMIDINE IMMUNOMODULATION Septic shock 

分 类 号：G43[文化科学—教育学]