TLR4 Agonist Monophosphoryl Lipid A Alleviated Radiation-Induced Intestinal Injury

TLR4 Agonist Monophosphoryl Lipid A Alleviated Radiation-Induced Intestinal Injury
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TLR4 激动剂单磷酰脂 A 减轻辐射引起的肠损伤

DOI:
10.1155/2019/2121095
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发表时间:
2019-01-01
影响因子:
4.1
通讯作者:
Gao, Fu
Gao, Fu
中科院分区:
医学3区
文献类型:
--
作者:
Guo, Jiaming;Liu, Zhe;Gao, Fu

文献摘要

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小肠是辐射损伤最敏感的器官之一,因此,研制高效、低毒的肠型放射病防护剂迫在眉睫。单磷酰脂质A(MPLA)在我们以前的研究中被发现具有辐射防护作用,但其对肠道辐射损伤的作用尚不清楚。本研究首次采用TUNEL法检测了放射损伤后小肠细胞凋亡的变化。随后,我们采用免疫荧光技术来评估体内不同生物标志物包括Ki 67、γ-H2 AX和防御素1的表达水平。采用RT-PCR方法检测各组大鼠外周血中炎性细胞因子的表达。提示MPLA可通过激活TLR 4信号通路和调节炎症细胞因子来保护肠道免受电离辐射损伤。本研究为新型TLR 4激动剂MPLA对IR诱导的肠道损伤的保护作用提供了新的思路。
The small intestine is one of the most sensitive organs to irradiation injury, and the development of high effective radioprotectants especially with low toxicity for intestinal radiation sickness is urgently needed. Monophosphoryl lipid A (MPLA) was found to be radioprotective in our previous study, while its effect against the intestinal radiation injury remained unknown. In the present study, we firstly determined the intestinal apoptosis after irradiation injury according to the TUNEL assay. Subsequently, we adopted the immunofluorescence technique to assess the expression levels of different biomarkers including Ki67, γ-H2AX, and defensin 1 in vivo. Additionally, the inflammatory cytokines were detected by RT-PCR. Our data indicated that MPLA could protect the intestine from ionizing radiation (IR) damage through activating TLR4 signal pathway and regulating the inflammatory cytokines. This research shed new light on the protective effect of the novel TLR4 agonist MPLA against intestine detriment induced by IR.