Muramyl Dipeptide Enhances Thermal Injury–Induced Inflammatory Cytokine Production and Organ Function Injury in Rats

Muramyl Dipeptide Enhances Thermal Injury–Induced Inflammatory Cytokine Production and Organ Function Injury in Rats
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DOI:
10.1097/shk.0000000000000164
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发表时间:
2014-08
期刊:
影响因子:
3.1
通讯作者:
Hui Liang;Xuemin Song;Xiao-jing Wu;Jian-guo Li;Yi Han;Yanlin Wang;Hui Li;Zongze Zhang;Lin-Li Le;Yang Xu
Hui Liang;Xuemin Song;Xiao-jing Wu;Jian-guo Li;Yi Han;Yanlin Wang;Hui Li;Zongze Zhang;Lin-Li Le;Yang Xu
中科院分区:
医学2区
文献类型:
--
作者:
Hui Liang;Xuemin Song;Xiao-jing Wu;Jian-guo Li;Yi Han;Yanlin Wang;Hui Li;Zongze Zhang;Lin-Li Le;Yang Xu

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烧伤后细菌感染是导致机体过度炎症反应和多器官损害的重要因素。胞壁酰二肽(MDP)是革兰氏阳性菌和革兰氏阴性菌启动天然免疫系统的关键结构。本研究的目的是确定MDP对大鼠热损伤诱导的炎症反应、器官功能损伤和死亡率的影响。雄性SD大鼠50只,随机分为3组:正常对照组、丹参组和MDP组。烫伤组仅造成20%体表面积的Ⅲ度烫伤。MDP组于烫伤后24 h经股静脉给予胞壁酰二肽5 mg·kg-1。酶联免疫吸附试验测定血浆炎症细胞因子水平。另取90只雄性SD大鼠随机分为3组,观察72 h存活率。单纯热损伤后,血浆白细胞介素6、白细胞介素10、干扰素和高迁移率族蛋白1水平,白色血细胞计数,血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素、肌酸激酶同工酶-MB、血尿素氮和肌酐浓度以及肺组织髓过氧化物酶活性均显著升高。MDP组的炎症反应、脏器功能损害及死亡率均高于单纯化疗组(P < 0.05)。这些数据表明,MDP加剧了热损伤诱导的炎症细胞因子的产生,伴随着多器官功能障碍综合征和高死亡率的大鼠。
ABSTRACT The bacterial infection following thermal injury is a very important factor of excessive inflammatory response and multiple organ damage. Muramyl dipeptide (MDP) is the key structure of gram-positive bacteria and gram-negative bacteria triggering the innate immune system. The aim of the present study was to determine the effect of MDP on thermal injury–induced inflammatory responses, organ function injury, and mortality in rats. Fifty male Sprague-Dawlay rats were randomly divided into three groups: normal control group, scald group, and MDP group. Scald group only suffered 20% total body surface area third-degree thermal injury. Muramyl dipeptide 5 mg·kg−1 was administered through the femoral vein at 24 h after thermal injury in the MDP group. Plasma inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. An additional 90 male Sprague-Dawley rats were randomly divided into three groups to observe the survival rate in 72 h. Plasma levels of interleukin-6, interleukin-10, interferon-, and high-mobility group box 1; the white blood cell counts; the serum concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatine kinase isoenzyme-MB, blood urea nitrogen, and creatinine; and the activity of lung tissue myeloperoxidase significantly increased after thermal injury alone. Compared with the scald group, MDP led to more serious inflammatory responses and organ function damage and higher mortality (P < 0.05, respectively). These data indicate that MDP exacerbates thermal injury–induced inflammatory cytokine production, accompanied by multiple organ dysfunction syndrome and high mortality in rats.