title: Myocardial protective effects of a c-Jun N-terminal kinase inhibitor in rats with brain death.
abstract: To investigate whether the mitochondrial apoptotic pathway mediates myocardial cell injuries in rats under brain death (BD), and observe the effects and mechanisms of the c-Jun N-terminal kinase (JNK) inhibitor SP600125 on cell death in the heart. Forty healthy male Sprague-Dawley (SD) rats were randomized into four groups: sham group (dural external catheter with no BD); BD group (maintain the induced BD state for 6 hrs); BD + SP600125 group (intraperitoneal injection of SP600125 10 mg/kg 1 hr before inducing BD, and maintain BD for 6 hrs); and BD + Dimethyl Sulphoxide (DMSO) group (intraperitoneal injection of DMSO 1 hr before inducing BD, and maintain BD for 6 hrs). Real-time quantitative PCR was used to evaluate mRNA levels of Cyt-c and caspase-3. Western blot analysis was performed to examine the levels of mitochondrial apoptosis-related proteins p-JNK, Bcl-2, Bax, Cyt-c and Caspase-3. TUNEL assay was employed to evaluate myocardial apoptosis. Compared with the sham group, the BD group exhibited increased mitochondrial apoptosis-related gene expression, accompanied by the elevation of p-JNK expression and myocardial apoptosis. As the vehicle control, DMSO had no treatment effects. The BD + SP600125 group had decreased p-JNK expression, and reduced mitochondrial apoptosis-related gene expression. Furthermore, the apoptosis rate of myocardial cells was reduced. The JNK inhibitor SP600125 could protect myocardial cells under BD through the inhibition of mitochondrial apoptosis-related pathways.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Cao
authors.affiliation: Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, China.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001926:Brain Death / Q000473:pathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000873:Anthracenes; D002316:Cardiotonic Agents; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: JNK inhibitor; apoptosis; brain death; heart transplantation