Effect of dexmedetomidine on lung ischemia‑reperfusion injury.
Effect of dexmedetomidine on lung ischemia‑reperfusion injury.
复制标题
DOI：
10.3892/mmr.2013.1867
复制
发表时间：
2014-02
影响因子：
3.4
通讯作者：
Guo L
中科院分区：
文献类型：
--
作者：
Jiang L;Li L;Shen J;Qi Z;Guo L
右美托咪定是一种特异性的选择性α2-肾上腺素能激动剂，不仅具有镇静和镇痛的作用，而且对脓毒症动物的脑缺血再灌注损伤具有保护作用和抑制炎症反应的作用。本研究旨在探讨右美托咪定能否减轻急性无菌肺损伤--缺血再灌注损伤所致的大鼠肺损伤。将SD大鼠随机分为6组：假手术组(Sham)、肺缺血再灌注(I/R)组、缺血前1 h静脉注射右美托咪定2.5μ/kg/h(Dex2.5)或5μg/kg/h(Dex5)、α2-肾上腺素能拮抗剂育亨宾(Dex+Yoh)和缺血前单独应用育亨宾(Yoh)组。通过肺组织病理变化、动脉血气、湿/干(w/d)重量比和髓过氧化物酶(MPO)活性评价肺损伤程度。采用酶联免疫吸附试验检测肺泡灌洗液中肿瘤坏死因子-α、白介素6和单核细胞趋化蛋白-1的浓度。用定量聚合酶链式反应检测肺组织Toll样受体4和髓系分化因子88(MyD88)的表达，用免疫印迹法检测c-jun氨基末端激酶(JNK)和细胞外信号调节蛋白(ERK)1/2的磷酸化水平。与I/R组比较，右美托咪定可显著减轻肺损伤，降低肺组织中肿瘤坏死因子-α、IL-6和单核细胞趋化蛋白-1的浓度，减轻肺组织重量/体重比和肺组织MPO活性。在肺I/R前1h静脉注射右美托咪胺可显著下调肺组织TLR4和MyD88mRNA的表达及磷酸化jnk和ERK1/2的水平。α2肾上腺素能拮抗剂育亨宾不能完全逆转右美托咪定对肺的保护作用。右旋美托咪定可减轻肺I/R损伤所致的肺损伤，抑制肺I/R损伤所致的无菌炎症反应。TLR4/MYD88/丝裂原活化蛋白激酶信号转导通路参与了右美托咪啶的保护机制，其机制可能与α2肾上腺素受体无关有关。
Dexmedetomidine, a specific selective α2-adrenergic agonist, does not only have the characteristics of being a sedative and analgesic, but also exhibits a protective role in brain ischemia-reperfusion injury and inhibits the inflammation in animals with sepsis. The objective of the present study was to investigate whether dexmedetomidine is capable of attenuating rat pulmonary damage induced by ischemia-reperfusion injury, which is a type of acute sterile lung injury. Sprague-Dawley rats were randomly assigned into six groups: The sham-operated (sham) group, the lung ischemia-reperfusion (I/R) group, intravenous injection of dexmedetomidine 2.5 μg/kg/h (Dex2.5) or 5 μg/kg/h (Dex5) for 1 h prior to ischemia, combination of α2-adrenergic antagonist yohimbine prior to dexmedetomidine pre-treatment (Dex+Yoh) and pre-administration of yohimbine alone (Yoh) prior to ischemia. Lung injury was assessed by the histopathological changes, arterial blood gas, wet/dry (w/d) weight ratio and myeloperoxidase (MPO) activity of the lung. The concentration of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in bronchoalveolar lavage fluid (BALF) was measured by an enzyme-linked immunosorbent assay. The expression of toll-like receptor-4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA in the lung were determined by quantitative PCR, and phosphorylated levels of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2 were determined by western blotting. Pre-treatment with dexmedetomidine significantly reduced the lung injury, w/d weight ratio and MPO activity, and decreased the concentration of TNF-α, IL-6 and MCP-1 in BALF compared with the I/R group. The expression of TLR4 and MyD88 mRNA and the levels of phosphorylated JNK and ERK1/2 in the lung tissue were markedly downregulated by intravenous injection of dexmedetomidne for 1 h prior to lung I/R. The protective effects of dexmedetomidine on the lung were not completely reversed by the α2-adrenergic antagonist, yohimbine. Pre-treatment with dexmedetomidine is capable of reducing pulmonary damage and inhibiting sterile inflammation induced by lung I/R injury. TLR4/MyD88/mitogen-activated protein kinase (MAPK) signaling is involved in the protective mechanism of dexmedetomidine through α2-adrenoceptor independence.
登录
查看更多内容
影响因子：
3.7
作者：
Reino DC;Pisarenko V;Palange D;Doucet D;Bonitz RP;Lu Q;Colorado I;Sheth SU;Chandler B;Kannan KB;Ramanathan M;Xu DZ;Deitch EA;Feinman R
通讯作者：
Feinman R
影响因子：
4.6
作者：
Arslan F;Keogh B;McGuirk P;Parker AE
通讯作者：
Parker AE
影响因子：
4.8
作者：
Ambrosio, G;Tritto, I
通讯作者：
Tritto, I
DOI：
10.1016/j.bbrc.2005.10.068
发表时间：
2005-12-16
影响因子：
3.1
作者：
Hua, F;Ha, TZ;Li, CF
通讯作者：
Li, CF
影响因子：
5.7
作者：
Nishina, K;Akamatsu, H;Niwa, Y
通讯作者：
Niwa, Y