Intensive Care Unit, Zhejiang Hospital, Hangzhou, Zhejiang 310013, China.
Chin Med J (Engl). 2013;126(10):1860-6.
Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats.
Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity.
Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge.
Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.
心肌细胞凋亡参与了脓毒症相关性心肌抑制的发病机制。然而，其潜在的机制尚不清楚。本研究旨在探讨脓毒症大鼠心脏细胞凋亡过程中线粒体损伤和线粒体诱导的氧化应激的作用。
72 只 Sprague-Dawley 大鼠随机分为对照组和接受脂多糖注射的脓毒症组。通过光镜和扫描电镜观察心脏组织形态变化，采用末端转移酶介导的 dUTP 缺口末端标记法检测心肌细胞凋亡，Western blot 检测核因子-κB 在心肌中的激活情况以评估心肌细胞凋亡。通过线粒体嵴形态和细胞色素 C 氧化酶的活性来评估线粒体损伤。通过线粒体脂质和蛋白质氧化来评估氧化应激，通过线粒体超氧化物歧化酶和谷胱甘肽过氧化物酶活性来评估抗氧化防御。
脓毒症诱导的炎症细胞浸润、心肌变性和水肿与时间有关。感染大鼠心脏在 24 小时可见扩张的毛细血管。与假手术组相比，脓毒症大鼠心脏细胞凋亡率在 6、12 和 24 小时呈时间依赖性增加（P<0.05）。脓毒症过程中，细胞质中核因子-κB p65 的表达逐渐减少，而细胞核中则逐渐增加，表明脓毒症刺激了核因子-κB 的逐步激活。线粒体嵴和细胞色素 C 氧化酶的活性随时间呈上升趋势。超氧化物歧化酶和谷胱甘肽过氧化物酶的活性在脂多糖攻击后 6 至 24 小时内下降，而线粒体脂质和蛋白质的氧化增加。
脓毒症刺激诱导心肌细胞凋亡和线粒体损伤。此外，通过改变对活性氧的防御，线粒体损伤可能在脓毒症期间的心肌细胞凋亡中发挥重要作用。
