脓毒症早期大鼠肾上腺线粒体损伤的研究

Adrenal mitochondrial injury in early stage of sepsis in rats

目的探讨脓毒症早期肾上腺线粒体损伤情况及其损伤机制。方法 30只SPF级雄性大鼠随机分为对照组、腹腔注射脂多糖(LPS)6h和24h组,实验组腹腔注射LPS10mg/kg。电镜观察线粒体结构并行Flameng评分;提取线粒体,以流式细胞仪检测线粒体膜电位,比色法检测线粒体内丙二醛(MDA)、一氧化氮(NO)含量及一氧化氮合成酶(NOS)活性等氧化应激指标。结果随脓毒症时间的进展,实验组较对照组血清皮质醇浓度增高;电镜下观察线粒体结构损伤,Flameng评分较对照组显著增加;流式细胞仪检测线粒体膜电位下降,但呈可逆趋势;线粒体内未检测到氧化应激因子的明显变化。结论脓毒症早期大鼠肾上腺功能无明显损伤,肾上腺线粒体可出现损伤性改变,但这种损伤呈可逆趋势,且线粒体未见明显的氧化应激反应,提示作为机体对抗损伤的应激和保护器官,肾上腺及其线粒体在脓毒症早期有较强的抗损伤和修复能力。

Objective To study the pathogenesis of adrenal mitochondrial dysfunction in septic rats. Methods Thirty SPF rats were randomized into 3 groups, including a normal control group and 2 sepsis groups receiving intraperitoneal injection of 10 mg/kg lipopolysaccharide （LPS） and observed at 6 and 24 h after the injection. The adrenal mitochondria were extracted from the rats at the corresponding time points for observation by electronic microscopy. The membrane potential of the mitochondria was detected by flow cytometry. The oxidative stress levels in the mitochondria （activities of NOS and levels of MDA and NO） were assessed. Results With the progression of sepsis, the serum levels of corticosterone in LPS groups increased significantly as compared with that in the control group. Ultrasructural observation of the adrenal mitochondria showed mild mitochondrial injury in LPS groups in comparison with the control group. The mitochondrial membrane potential was lowered in the LPS groups, but all these changes appeared to be reversible. The activities of NOS and the levels of MDA and NO showed no significant difference between the sepsis groups and the control group. Conclusions No obvious adrenal dysfunction occurs in the early stage of sepsis in rats. Mitochondrial injury, which is reversible, occurs in early sepsis without obvious evidence of oxidative stress injury in the adrenal mitochondria, suggesting a strong resistance and capacity of self-repair of the adrenal gland and the mitochondria against sepsis-induced injury.