Open AccessMyocardial protective effects of a c‐Jun N‐terminal kinase inhibitor in rats with brain death
Author(s) -
Guo Wenzhi,
Cao Shengli,
Yan Bing,
Zhang Gong,
Li Jie,
Zhao Yongfu,
Zhang Shuijun
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12676
Subject(s) - apoptosis , tunel assay , c jun , kinase , western blot , intraperitoneal injection , programmed cell death , mitochondrion , microbiology and biotechnology , chemistry , medicine , biology , andrology , endocrinology , biochemistry , gene , transcription factor
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 SP 600125 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 + SP 600125 group (intraperitoneal injection of SP 600125 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 + SP 600125 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 SP 600125 could protect myocardial cells under BD through the inhibition of mitochondrial apoptosis‐related pathways.