5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice.
5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice.
复制标题
5-HT 导致盲肠结扎和穿刺引起的小鼠败血症死亡率增加
DOI：
10.1155/2017/6374283
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发表时间：
2017
影响因子：
4.6
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Zhang J;Bi J;Liu S;Pang Q;Zhang R;Wang S;Liu C
脓毒症是由宿主对感染的反应失调引起的危及生命的器官功能障碍，死亡率高。5-羟色胺（5-HT）是炎症反应的重要调节因子。本研究旨在探讨5-羟色胺（5-HT）在盲肠结扎穿孔（CLP）诱导的脓毒症小鼠模型中的作用。对C57 B/6野生型（WT）小鼠和色氨酸羟化酶1（TPH 1）敲除（KO）小鼠进行CLP。结果表明，5-HT充足组小鼠在CLP诱导的脓毒症和脓毒性休克中的存活率显著低于5-HT缺乏组。KO-CLP脓毒症组的临床评分低于WT-CLP脓毒症组。同时，KO-CLP脓毒症组小鼠的体温高于WT-CLP脓毒症组，且更接近CLP后24 h的正常体温。组织病理学分析显示，5-HT明显加重了脓毒症时腹膜、肺、肝、肾、肠组织和心脏的组织学损害。此外，KO-CLP脓毒症组的TNF-α、IL-6、细菌载量、MPO和ROS水平显著低于WT-CLP脓毒症组。总之，5-HT通过促进血清细胞因子和细菌负荷以及促进脓毒症过程中的氧化应激来驱动死亡率并加剧器官功能障碍。
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.