| First Author | Xu ZQ | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 37709 | PubMed ID | 27874086 |
| Mgi Jnum | J:336836 | Mgi Id | MGI:6224130 |
| Doi | 10.1038/srep37709 | Citation | Xu ZQ, et al. (2016) Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through alpha7nAChR-dependent JAK2-STAT3 signaling. Sci Rep 6:37709 |
| abstractText | Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating alpha7 nicotinic acetylcholine receptor (alpha7nAChR). 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, TNFalpha, IL-6 and IL-10 in compressed muscle. These effects were attenuated by alpha7nAChR 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 (alpha7nAChR antagonist) and alpha7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of alpha7nAChR-dependent JAK2-STAT3 signaling pathway. |
