WITHDRAWN: Lumbrokinase regulates endoplasmic reticulum stress through IRE1 signaling to improve neurological deficits in ischemic stroke

Abstract

Background Ischemic stroke is characterized by the loss of cerebral blood flow, which frequently leads to neurological deficits. Therefore, minimizing post-stroke functional disability is an important research topic. The fibrinogen-depleting agent lumbrokinase has been used to improve myocardial perfusion in symptomatic stable angina and to prevent secondary ischemic stroke. In this study, we aimed to clarify the neuroprotection of lumbrokinase on ischemic stroke and whether improve neurological dysfunction. We explored the neuroprotection and the underlying mechanisms of lumbrokinase in C57BL/6 mice subjected to permanent middle cerebral artery occlusion. Results Lumbrokinase at 1 mg/kg significantly attenuated the infarct volume and improved the neurological dysfunction. Lumbrokinase dramatically decreased the expressions of the endoplasmic reticulum (ER) transmembrane receptor protein inositol-requiring enzyme-1 (IRE1) and its downstream transcription factor, X-box binding protein-1, caspase-12, and nuclear factor kappa B activity. Moreover, lumbrokinase significantly inhibited apoptosis and autophagy and decreased the expression levels of the NOD-like receptor 3 inflammasome, caspase-1, and interleukin-1β compared with the vehicle treatment. Conclusions We suggest that post-stroke treatment with lumbrokinase protects against ischemic stroke by regulating ER stress through the IRE1 signaling pathways to inhibit apoptosis, autophagy, and inflammatory responses.