Mitochondria-targeted peptide SS-31 protects septic rats against vascular permeability

• Main Authors: ZHU Yu, WU Yue, ZHANG Jie, TIAN Kunlun, PENG Xiaoyong
• Format: Article
• Language: zho
• Published: Editorial Office of Journal of Third Military Medical University 2019-02-01
• Series: Di-san junyi daxue xuebao
• Subjects: mitochondria-targeted peptide ss-31; septic rats; oxidative stress; permeability
• Online Access: http://aammt.tmmu.edu.cn/Upload/rhtml/201808002.htm

Objective To investigate the protective effect of mitochondria-targeted peptide SS-31 on vascular permeability in septic rats and explore its underlying mechanism. Methods Forty Sprague-Dawley rats (12 weeks old, both genders, weighting about 220 g) were equally and randomly divided into 5 groups, sham operation group (sham group), sepsis group, sepsis+conventional treatment (CT) group, sepsis+early injection of SS-31 group and sepsis+later injection of SS-31 group. Cecal ligation and puncture (CLP) was performed to establish septic rats. Lactated Ringer's solution (containing cefuroxime sodium and dopamine) or the solution containing 3 mg/kg SS-31 were injected through femoral vein to the rats of sepsis+CT group or sepsis+later injection group, and the agent was also given to the rats of the sepsis+early injection group in 30 min before CLP. Fluorescence albumin transmissivity in the tissue homogenate was measured for the vascular permeability of the lungs and kidneys. Intestinal permeability was measured by Evans blue staining. Primarily isolated and cultured pulmonary vein endothelial cells were treated with lipopolysaccharide (LPS group), and SS-31 followed by LPS addition (LPS+SS-31 group). Then the expression level of zonula occludes-1 (ZO-1), intensity of transmembrane resistance (TER), and generation of reactive oxygen species (ROS) were detected in the endothelial cells. The cells cultured in serum-free medium for 24 h served as normal control cells. Results ① The sepsis group had significantly more obvious vascular permeability of the lungs, kidneys and intestine, and damaged mitochondrial function when compared with the sham group (P < 0.01). Though conventional treatment reduced the permeability and relieved mitochondrial dysfunction, the effects were not significant than the conditions in the sepsis group (P>0.05). Both early and later injection of SS-31 notably decreased the permeability and improved mitochondrial function than the conventional treatment (P < 0.01), with the effects of early injection more significant. ② Compared with the normal control cells, LPS significantly decreased the expression of ZO-1, leading to disordered cell structure and significantly reduced TER, but increased the generation of ROS. SS-31 pretreatment could enhance ZO-1 expression and TER, and decrease ROS content. Conclusion SS-31 exerts protective effect on vascular permeability of septic rats, which was probably related to the mitochondrial oxidative stress.