Lactoferrin moderates LPS-induced hypotensive response and gut injury in rats

Lactoferrin moderates LPS-induced hypotensive response and gut injury in rats
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DOI:
10.1016/j.intimp.2012.12.009
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发表时间:
2013-02-01
影响因子:
5.6
通讯作者:
Kruzel, Marian L.
Kruzel, Marian L.
中科院分区:
医学2区
文献类型:
--
作者:
Doursout, Marie-Francoise;Horton, Haley;Kruzel, Marian L.

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低血压是低血压的一种生理状态,其原因从脱水到潜在的严重医学疾病。本研究的目的是评估乳铁蛋白(LF),一种天然的免疫调节剂,抑制LPS诱导的大鼠低血压的效用。LF先前已证明在免疫应答的介导中的作用,包括在急性炎症期间控制炎性细胞因子的产生。在LPS注射前1 h或18 h,通过管饲法向大鼠施用LF。连续记录LPS给药后6 h的心率(HR)和平均动脉压(MAP)。在血液动力学测量的同时,检查血清中TNF-α、IL-6和TGF-β的产生。处死时,对近端十二指肠进行组织病理学分析。在LPS诱导的低血压大鼠中,LF在LPS诱导的低血压大鼠前1h给予保护。当在LPS攻击前18 h给予LF作为预处理时,对MAP的保护作用也是明显的,尽管这种作用减弱。对于所有组,LF预处理导致LPS给药后HR的微小但不显著的改善。此外,当大鼠在LPS前1小时给予LF时,它们显示出血清TNF-α和IL-6产生的显著降低。LF不影响血清TGF-β的产生水平。非常重要的是,LF能够赋予组织病理学保护肠组织后LPS管理,为1和18小时LF预处理组。这些研究表明LF控制低血压的临床应用潜力。由爱思唯尔公司出版
Hypotension is a physiologic state of low blood pressure, the causes of which range from dehydration to underlying serious medical disorders. The aim of this study was to assess the utility of lactoferrin (LF), a natural immunomodulator, to restrain LPS-induced hypotension in rats. LF has previously demonstrated a role in mediation of immune responses, including control of inflammatory cytokine production during acute inflammation. Rats were administered with LF by gavage at I h or 18 h prior to LPS injections. Heart rate (HR) and mean arterial blood pressure (MAP) were continuously recorded post LPS administration for 6 h. Simultaneously to hemodynamic measurements, serum was examined for TNF-alpha, IL-6, and TGF-beta production. At termination, the proximal duodenum was subjected to histopathological analysis. LF administered at 1 h prior to LPS protected rats from the LPS-induced hypotension. The protective effect on MAP was also apparent when LF was administered as a pretreatment 18 h prior to LPS challenge, although the effect was lessened. For all groups, LF pretreatment led to a minor, but insignificant, improvement in HR post LPS administration. In addition, when rats were given LF 1 h before LPS, they showed a significant decrease in serum TNF-alpha and IL-6 production. LF did not affect the production level of serum TGF-beta. Of high importance, LF was able to confer histo-pathological protection of intestinal tissue post LPS administration, for both the I hand 18 h LF pretreatment groups. These studies indicate a potential for clinical utility of LF to control hypotension. Published by Elsevier B.V.