Role of damaged mitochondria in cardiocyte apoptosis in septic rats
10.3760/cma.j.issn.1671-0282.2012.11.009
- VernacularTitle:线粒体损伤在脓毒症大鼠心肌细胞凋亡中的作用
- Author:
Li LI
;
Jing YAN
;
Changqin CHEN
;
Shijin GONG
;
Haiwen DAI
;
Yihua YU
;
Guolong CAI
;
Jin CHEN
;
Qianghong Xü
- Publication Type:Journal Article
- Keywords:
Sepsis;
Myocardial injury;
Cell apoptosis;
Mitochondrial;
Nuclear factor-kappa B
- From:
Chinese Journal of Emergency Medicine
2012;21(11):1221-1225
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of damaged mitochondria in cardiac cell apoptosis in septic rats and the possible mechanism involved.Methods Seventy-two Sprague-Dawley rats were randomly (random number) divided into negative control group (n =18) and septic group (further divided into three groups as per rats sacrificed 6 h,12 h,and 24 h after endotoxin injection intra-peritoneally,n =18).The hearts of rats were taken.The changes of cardiac morphology were observed under light microscope and scanning electron microscope.Cell apoptosis in situ were examined by using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B (NF-κB) activation in myocardium was detected by using Western blotting to estimate myocardial cell apoptosis.Mitochondrial lipid and protein oxidation were measured to assess oxidative stress,and mitochondrial superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined to estimate antioxidant defense.Results Septic induced inflammatory cells infiltration,myocardium degeneration and effusion in a time-dependent manner.A remarkable expansion of capillaries could be observed in the hearts of infected rats at post-challenge of 24 h.Compared with sham-treated rats,the percentage of apoptosis increased in a time-dependent manner in the hearts of infected rats at 6 h,12 h,24 h of post-injection (P ＜0.05).The concentration of NF-κB p65 in the cytosol decreased gradually and increased in the nucleus during sepsis in a time-dependent manner (P ＜0.05),indicating that septic challenge provoked progressive activation of NF-κB.Mitochondrial cristae disappeared in 6 h of challenge,and significant mitochondrial cristae disappearance,vacuolization,and rupture of mitochondria membrane became markedly obvious 12 and 24 h later.Both SOD and GPx activities decreased,while mitochondrial lipid and protein oxidation increased in a time-dependent manner after 6-24 h of challenge (P ＜ 0.05).Conclusions Septic challenge induced myocardial apoptosis and mitochondrial damage.Further,damaged mitochondria might play an important role by means of alteration of defenses against reactive oxygen species in myocardial cell apoptosis during sepsis.
