Dexmedetomidine ameliorates acute lung injury following orthotopic autologous liver transplantation in rats probably by inhibiting Toll-like receptor 4-nuclear factor kappa B signaling.
Dexmedetomidine ameliorates acute lung injury following orthotopic autologous liver transplantation in rats probably by inhibiting Toll-like receptor 4-nuclear factor kappa B signaling.
复制标题
右美托咪定可能通过抑制 Toll 样受体 4-核因子 kappa B 信号传导改善大鼠原位自体肝移植后的急性肺损伤
DOI：
10.1186/s12967-015-0554-5
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发表时间：
2015-06-13
影响因子：
7.4
通讯作者：
Cai J
中科院分区：
文献类型：
--
作者：
Chi X;Wei X;Gao W;Guan J;Yu X;Wang Y;Li X;Cai J
目的探讨右美托咪定（Dex）预处理对大鼠原位自体肝移植（OALT）后急性肺损伤（ALI）的保护作用及其机制。将48只大鼠随机分为6组（每组n = 8）接受10 µg/kg Dex、50 µg/kg Dex、50 µ g/kg Dex +非特异性α2-肾上腺素能受体（AR）拮抗剂阿替美唑、50 µg/kg Dex +特异性α2B/C-AR拮抗剂ARC-239、50 µg/kg Dex +特异性α2A-AR拮抗剂BRL-44408，或者等量的生理盐水假手术组大鼠（n = 8）行麻醉诱导、开腹、门静脉分离，不进行肝脏缺血再灌注。肺组织切片用苏木精和伊红（HE）染色以观察损伤。检测Toll样受体4（TLR 4）、磷酸化核因子（NF）-κB p65亚单位及炎性细胞因子的表达。大鼠在OALT后表现出组织学肺损伤评分增加和肺水肿。50 μg/kg Dex预处理可减轻OALT诱导的大鼠肺损伤，其机制可能与抑制TLR 4-NF-κB信号通路的激活有关。阿替美唑或BRL-44408可阻断Dex的保护作用，但ARC-239不能阻断Dex的保护作用，表明Dex的这些作用至少部分由α2A-AR介导。Dex对OALT后的ALI具有保护作用，这种保护作用与抑制TLR 4-NF-κB信号通路有关。因此，地塞米松预处理可能是一种有效的方法，以减少肝移植引起的肺损伤。
To investigate whether pretreatment with dexmedetomidine (Dex) has a protective effect against acute lung injury (ALI) in an orthotopic autologous liver transplantation (OALT) rat model and to explore the mechanisms responsible for the protective effect of Dex against lung injury. Forty-eight rats underwent OALT and were randomly divided into six groups (n = 8 in each group) that received 10 µg/kg Dex, 50 µg/kg Dex, 50 µg/kg Dex + nonspecific α2-adrenergic receptor (AR) antagonist atipamezole, 50 µg/kg Dex + specific α2B/C-AR antagonist ARC-239, 50 µg/kg Dex + specific α2A-AR antagonist BRL-44408, or the same amount of normal saline. The sham rats (n = 8) underwent anesthesia induction, laparotomy, and separation of the portal vein without liver ischemia and reperfusion. Lung tissue sections were stained with hematoxylin and eosin (HE) to visualize the damage. The expression of Toll-like receptor 4 (TLR4) and the phospho-nuclear factor (NF)-κB p65 subunit as well as inflammatory cytokines was measured. Rats exhibited increased histological lung injury scores and pulmonary edema following OALT. Pretreatment with 50 μg/kg Dex attenuated OALT-induced lung injury in rats, probably by inhibiting the activation of the TLR4–NF-κB signaling pathway. The protective effect of Dex could be blocked by atipamezole or BRL-44408, but not by ARC-239, suggesting these effects of Dex were mediated, at least in part, by the α2A-AR. Dex exerts protective effects against ALI following OALT, and this protection is associated with the suppression of TLR4–NF-κB signaling. Thus, pretreatment with Dex may be a useful method for reducing lung damage caused by liver transplantation.
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影响因子：
3.2
作者：
Kaplan J;Nowell M;Chima R;Zingarelli B
通讯作者：
Zingarelli B
影响因子：
4.3
作者：
Feltracco, Paolo;Carollo, Cristiana;Ori, Carlo
通讯作者：
Ori, Carlo
影响因子：
5.7
作者：
Paris, A;Mantz, J;Gressens, P
通讯作者：
Gressens, P
影响因子：
1.7
作者：
Smith, Lincoln S.;Kajikawa, Osamu;Frevert, Charles W.
通讯作者：
Frevert, Charles W.
影响因子：
5.8
作者：
Deng, Jane C.;Standiford, Theodore J.
通讯作者：
Standiford, Theodore J.