Mild hypothermia alleviates diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis

摘要

Diabetic patients manifest with more severe neurological deficits than non-diabetes after ischemic stroke. It has been shown that hypothermia has neuroprotective effects on cerebral ischemia, but whether it is effective for cerebral ischemia in diabetic patients remains unknown. The aim of this study was to investigate whether hypothermia can alleviate cerebral ischemic injury in diabetic rats and the regulation of autophagy and pyroptosis of the treatment. We introduced permanent middle cerebral artery occlusion (pMCAO) in a model of type 2 diabetic rats prepared by high-fat diet combined with intraperitoneal injection of STZ in vivo and mimicked cerebral ischemia with diabetes by employing high glucose stimulation and oxygen glucose deprivation/reoxygenation (OGD/R) in vitro. Moreover, 3-methyladenine and bafilomycin A1 were used to evaluate the association between autophagy and pyroptosis in vitro. Our results showed that diabetes aggravated neurological deficits, increased the volume of cerebral infarction and brain edema as well as the blood brain barrier permeability after cerebral ischemia, which were alleviated by mild hypothermia. Compared with the pMCAO model in non-diabetic rats and OGD/R model without high glucose stimulation in vitro, the expression of P62, NOD-like receptor protein 3 (NLRP3), cleaved caspase-1 and Gasdermin-N increased and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) II/I decreased in the pMCAO model in diabetic rats and OGD/R model with high glucose stimulation, which could be reversed by mild hypothermia. In conclusion, mild hypothermia alleviated diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis.