科研之友
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摘要
On-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine (Ani) is widely used in China for treatment of shock, and activation of alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) mediates such antishock effect. The present work was designed to test whether activation of alpha 7nAChR with Ani decreased mortality in crush syndrome shortly after decompression. Spragu-eDawley rats and C57BL/6 mice with crush syndrome were injected with Ani (20 mg/kg and 28 mg/kg respectively, i.p.) 30 min before decompression. Survival time, serum potassium, insulin, and glucose levels were observed shortly after decompression. Involvement of alpha 7nAChR was verified with methyllycaconitine (selective alpha 7nAChR antagonist) and PNU282987 (selective alpha 7nAChR agonist), or in alpha 7nAChR knockout mice. Effect of Ani was also appraised in C2C12 myotubes. Ani reduced mortality and serum potassium and enhanced insulin sensitivity shortly after decompression in animals with crush syndrome, and PNU282987 exerted similar effects. Such effects were counteracted by methyllycaconitine or in alpha 7nAChR knockout mice. Mortality and serum potassium in rats with hyperkalemia were also reduced by Ani. Phosphorylation of Na/K-ATPase was enhanced by Ani in C2C12 myotubes. Inhibition of tyrosine kinase on insulin receptor, phosphoinositide 3-kinase, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Na/K-ATPase counteracted the effect of Ani on extracellular potassium. These findings demonstrated that activation of alpha 7nAChR could decrease on-site mortality in crush syndrome, at least in part based on the decline of serum potassium through insulin signaling-Na/K-ATPase pathway.
- 出版日期2016-3-29
- 单位中国人民解放军济南军区总医院; 中国人民解放军第二军医大学
