消化道选择性去污改善大鼠严重烧伤诱导的胰岛素抵抗。
Selective decontamination of the digestive tract ameliorates severe burn-induced insulin resistance in rats.
作者信息
Li Jun, Zhu Liang, Xu Ming, Han Juntao, Bai Xiaozhi, Yang Xuekang, Zhu Huayu, Xu Jie, Zhang Xing, Gong Yangfan, Hu Dahai, Gao Feng
机构信息
Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an, China; Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Medical Education, Fourth Military Medical University, Xi'an, China.
出版信息
Burns. 2015 Aug;41(5):1076-85. doi: 10.1016/j.burns.2014.12.018. Epub 2015 Feb 21.
BACKGROUND
Severe burns often initiate the prevalence of hyperglycemia and insulin resistance, significantly contributing to adverse clinical outcomes. However, there are limited treatment options. This study was designed to investigate the role and the underlying mechanisms of oral antibiotics to selectively decontaminate the digestive tract (SDD) on burn-induced insulin resistance.
MATERIALS AND METHODS
Rats were subjected to 40% of total body surface area full-thickness burn or sham operation with or without SDD treatment. Translocation of FITC-labeled LPS was measured at 4h after burn. Furthermore, the effect of SDD on post-burn quantity of gram-negative bacteria in gut was investigated. Serum or muscle LPS and proinflammatory cytokines were measured. Intraperitoneal glucose tolerance test and insulin tolerance test were used to determine the status of systemic insulin resistance. Furthermore, intracellular insulin signaling (IRS-1 and Akt) and proinflammatory related kinases (JNK and IKKβ) were assessed by western blot.
RESULTS
Burn increased the translocation of LPS from gut 4h after injury. SDD treatment effectively inhibited post-burn overgrowth of gram-negative enteric bacilli in gut. In addition, severe burns caused significant increases in the LPS and proinflammatory cytokines levels, activation of proinflammatory related kinases, and systemic insulin resistance as well. But SDD treatment could significantly attenuate burn-induced insulin resistance and improve the whole-body responsiveness to insulin, which was associated with the inhibition of gut-derived LPS, cytokines, proinflammatory related kinases JNK and IKKβ, as well as activation of IRS-1 and Akt.
CONCLUSIONS
SDD appeared to have an effect on proinflammatory signaling cascades and further reduced severe burn-induced insulin resistance.
背景
严重烧伤常引发高血糖和胰岛素抵抗，这对不良临床结局有显著影响。然而，治疗选择有限。本研究旨在探讨口服抗生素选择性肠道去污（SDD）对烧伤诱导的胰岛素抵抗的作用及潜在机制。
材料与方法
对大鼠进行40%体表面积的全层烧伤或假手术，分为有无SDD治疗组。烧伤后4小时测量异硫氰酸荧光素标记的脂多糖（LPS）的移位情况。此外，研究SDD对烧伤后肠道革兰氏阴性菌数量的影响。检测血清或肌肉中的LPS和促炎细胞因子。采用腹腔葡萄糖耐量试验和胰岛素耐量试验来确定全身胰岛素抵抗状态。此外，通过蛋白质印迹法评估细胞内胰岛素信号通路（胰岛素受体底物-1和蛋白激酶B）和促炎相关激酶（应激活化蛋白激酶和IκB激酶β）。
结果
烧伤后4小时肠道LPS移位增加。SDD治疗有效抑制烧伤后肠道革兰氏阴性肠杆菌的过度生长。此外，严重烧伤导致LPS和促炎细胞因子水平显著升高，促炎相关激酶激活，以及全身胰岛素抵抗。但SDD治疗可显著减轻烧伤诱导的胰岛素抵抗，改善全身对胰岛素的反应性，这与抑制肠道来源的LPS、细胞因子、促炎相关激酶应激活化蛋白激酶和IκB激酶β，以及激活胰岛素受体底物-1和蛋白激酶B有关。
结论
SDD似乎对促炎信号级联反应有影响，并进一步降低严重烧伤诱导的胰岛素抵抗。
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