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Role of JAK2-STAT3 pathway in reduction of myocardial ischemia-reperfusion injury by sufentanil postconditioning in dogs

Lixia Nie, Shouyuan Tian, Yu-jie Meng, Yan Gao, Chen-sheng Duan, Baojiang Liu

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Abstract

Objective To investigate the role of Janus kinese 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in dogs.Methods Twenty-four healthy dogs of either sex,weighing 10-15 kg,were randomly divided into 4 groups (n =6 each):sham operation group (group S); I/R group; sufentanil postconditioning group (group PO) and sufentanil postconditioning + specific JAK2 inhibitor AG490 group (group AG).In groups I/R,PO and AG,myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.In groups PO and AG,sufentanil 0.6 μg/kg was infused intravenously over 5 min before reperfusion and in addition in group AG,AG490 1 mg/kg was injected intravenously before sufentanil infusion.Myocardial specimens were taken at the end of 120 min reperfusion for microscopic examination and determination of the expression of caspase-3 and p-STAT3 by immuno-histochemistry and myocardial cell apoptosis index (AI) by TUNEL.Results AI and the expression of caspase-3 and p-STAT3 were significantly higher in groups I/R,PO and AG than in group S ( P ＜ 0.05).Compared with group I/R,AI and the expression of caspase-3 were significantly decreased in groups PO and AG,the expression of p-STAT3 was significantly increased in group PO,and the expression of p-STAT3 was significantly decreased in group AG ( P ＜ 0.05).AI and the expression of caspase-3 were significantly higher and the expression of p-STAT3 was significantly lower in group AG than in group PO (P ＜ 0.05).The pathologic changes were significantly attenuated in group PO compared with groups I/R and AG.Conclusion JAK2-STAT3 pathway is involved in reduction of myocardial I/R injury by sufentanil postconditioning in dogs. Key words: Janus kinase 2;  STAT3 transcription factor;  Sufentanil;  Myocardial reperfusion injury; Postconditioning

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Objective To investigate the role of Janus kinese 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in dogs.Methods Twenty-four healthy dogs of either sex,weighing 10-15 kg,were randomly divided into 4 groups (n =6 each):sham operation group (group S); I/R group; sufentanil postconditioning group (group PO) and sufentanil postconditioning + specific JAK2 inhibitor AG490 group (group AG).In groups I/R,PO and AG,myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.In groups PO and AG,sufentanil 0.6 μg/kg was infused intravenously over 5 min before reperfusion and in addition in group AG,AG490 1 mg/kg was injected intravenously before sufentanil infusion.Myocardial specimens were taken at the end of 120 min reperfusion for microscopic examination and determination of the expression of caspase-3 and p-STAT3 by immuno-histochemistry and myocardial cell apoptosis index (AI) by TUNEL.Results AI and the expression of caspase-3 and p-STAT3 were significantly higher in groups I/R,PO and AG than in group S ( P ＜ 0.05).Compared with group I/R,AI and the expression of caspase-3 were significantly decreased in groups PO and AG,the expression of p-STAT3 was significantly increased in group PO,and the expression of p-STAT3 was significantly decreased in group AG ( P ＜ 0.05).AI and the expression of caspase-3 were significantly higher and the expression of p-STAT3 was significantly lower in group AG than in group PO (P ＜ 0.05).The pathologic changes were significantly attenuated in group PO compared with groups I/R and AG.Conclusion JAK2-STAT3 pathway is involved in reduction of myocardial I/R injury by sufentanil postconditioning in dogs. Key words: Janus kinase 2;  STAT3 transcription factor;  Sufentanil;  Myocardial reperfusion injury; Postconditioning

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Available abstract

Objective To investigate the role of Janus kinese 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in dogs.Methods Twenty-four healthy dogs of either sex,weighing 10-15 kg,were randomly divided into 4 groups (n =6 each):sham operation group (group S); I/R group; sufentanil postconditioning group (group PO) and sufentanil postconditioning + specific JAK2 inhibitor AG490 group (group AG).In groups I/R,PO and AG,myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.In groups PO and AG,sufentanil 0.6 μg/kg was infused intravenously over 5 min before reperfusion and in addition in group AG,AG490 1 mg/kg was injected intravenously before sufentanil infusion.Myocardial specimens were taken at the end of 120 min reperfusion for microscopic examination and determination of the expression of caspase-3 and p-STAT3 by immuno-histochemistry and myocardial cell apoptosis index (AI) by TUNEL.Results AI and the expression of caspase-3 and p-STAT3 were significantly higher in groups I/R,PO and AG than in group S ( P ＜ 0.05).Compared with group I/R,AI and the expression of caspase-3 were significantly decreased in groups PO and AG,the expression of p-STAT3 was significantly increased in group PO,and the expression of p-STAT3 was significantly decreased in group AG ( P ＜ 0.05).AI and the expression of caspase-3 were significantly higher and the expression of p-STAT3 was significantly lower in group AG than in group PO (P ＜ 0.05).The pathologic changes were significantly attenuated in group PO compared with groups I/R and AG.Conclusion JAK2-STAT3 pathway is involved in reduction of myocardial I/R injury by sufentanil postconditioning in dogs. Key words: Janus kinase 2;  STAT3 transcription factor;  Sufentanil;  Myocardial reperfusion injury; Postconditioning

Key concepts: Sufentanil, Reperfusion injury, Medicine, TUNEL assay, STAT3, Anesthesia, Apoptosis, Ischemia

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Role of JAK2-STAT3 pathway in reduction of myocardial ischemia-reperfusion injury by sufentanil postconditioning in dogs — Research Paper | ScholarLens