Role of JAK2/STAT3 signaling pathway in brain injury induced by myocardial ischemia-reperfusion in diabetic rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathway on the brain injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods Pathogen-free male Sprague-Dawley rats,weighing 200-220 g,were used in this study.Diabetes mellitus was induced by intraperitoneal 1％ streptozotocin 60 mg/kg and confirmed by blood glucose level ≥ 16.7 mmol/L 3 days later.Twenty-four rats with diabetes mellitus were randomly allocated into 3 groups (n =8 each) using a random number tablesham operation group (group S),I/R group,and myocardial I/R + AG490 (JAK inhibitor) group (group ⅠA).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min,followed by 120 min of reperfusion in the rats anesthetized with pentobarbital sodium.AG490 3 mg/kg was injected intravenously at 20 min before reperfusion in group IA.The rats were sacrificed at 120 min of reperfusion,and the brains were removed for determination of caspase-3 and nuclear factor kappa B (NF-κB) activities (using colorimetric method),cell apoptosis (by TUNEL),and expression of interleukin-1 (IL-1),IL-6,IL-8,Bax,Bcl-2,cytochrome C (Cyt c),phosphorylated JAK2 (p-JAK2),and phosphorylated STAT3 (p-STAT3) (by Western blot).Apoptosis index was calculated.Results Compared with group S,the expression of Bax,Cyt c,IL-1,IL-6,IL-8,p-JAK2 and p-STAT3 was significantly up-regulated,the expression of Bcl-2 was down-regulated,and NF-κB and caspase-3 activities and apoptosis index were increased in I/R and IA groups (P＜0.05).Compared with group I/R,the expression of Bax,Cyt c,IL-1,IL-6,IL-8,p-JAK2 and p-STAT3 was significantly down-regulated,the expression of Bcl-2 was up-regulated,and NF-κB and caspase-3 activities and apoptosis index were decreased in group IA (P＜0.05).Conclusion Inflammatory responses mediated by JAK2/STAT3 signaling pathway are involved in the brain injury induced by myocardial I/R in diabetic rats.