Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling.
Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling.
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联合使用山莨菪碱和新斯的明通过 α7nAChR 依赖性 JAK2-STAT3 信号传导拯救急性致死性挤压综合征
DOI：
10.1038/srep37709
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发表时间：
2016-11-22
影响因子：
4.6
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Xu ZQ;Shao BZ;Ke P;Liu JG;Liu GK;Chen XW;Su DF;Liu C
以前我们发现Ani（山莨菪碱）/Neo（新斯的明）联合应用通过激活α7烟碱乙酰胆碱受体（α 7 nAChR）产生抗休克作用。在这项研究中，我们的目的是探讨Ani/Neo联合治疗急性致死性挤压综合征（CS）的治疗效果和潜在机制。Ani/Neo联合应用可提高CS大鼠和家兔的24 h存活率，改善血流动力学，降低血清肌酸激酶、肌酸激酶MB同工酶、血尿素氮、肌酐、K+水平。能降低CS大鼠血清和肌肉组织中H_2O_2、髓过氧化物酶（MPO）和一氧化氮（NO）的含量。Ani/Neo联合应用可提高CS小鼠24 h存活率，降低压缩肌肉中H2 O2、MPO、NO、TNFα、IL-6和IL-10水平。α 7 nAChR敲除（KO）可减弱上述效应。Ani/Neo联合应用可抑制CS诱导的Janus激酶2（JAK 2）磷酸化水平和信号转导子和转录激活子3（STAT 3）磷酸化水平的降低。Ani/Neo对CS小鼠的上述作用可被α 7 nAChR拮抗剂甲基甘草次酸（methyllycaconitine）和α 7 nAChR KO所抵消。总的来说，我们的结果表明，Ani/Neo组合可以在CS中产生治疗效果。其机制与α 7 nAChR依赖的JAK 2-STAT 3信号通路的激活有关。
Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway.
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影响因子：
44.1
作者：
通讯作者：
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影响因子：
8.8
作者：
Liu, Chong;Shen, Fu-Ming;Su, Ding-Feng
通讯作者：
Su, Ding-Feng
影响因子：
10.8
作者：
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通讯作者：
Chen, Xiongwen
影响因子：
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作者：
Correa Leite, Paulo Emilio;Gandia, Luis;Quirico-Santos, Thereza
通讯作者：
Quirico-Santos, Thereza
影响因子：
8.1
作者：
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通讯作者：
Su, Dingfeng