【摘要】 目的 探究线粒体靶向抗氧化剂SS-31对脓毒症小鼠模型急性肝损伤的作用。方法 将24只C57BL/6J成年雄性小鼠随机分为control 组、control+SS-31组、脂多糖(LPS)组(脓毒症组)、LPS+SS-31组，每组6只。小鼠腹腔注射LPS(10 mg/kg)制备脓毒症急性肝损伤模型或对照组腹腔注射等体积PBS液，继之腹腔注射SS-31(10 mg/kg)进行治疗或对照组腹腔注射等体积生理盐水, 12 h后ELISA法检测ALT、AST、活性氧(ROS)、超氧化物歧化酶(SOD)、TNFα、IL-1β、IL-6水平,HE染色观察肝脏组织病理学。计量资料多组间比较采用单因素方差分析，进一步两两比较采用LSD-t检验。结果 与LPS组相比,LPS+SS-31组小鼠血清中ALT[(140.05±12.22) U/L vs (102.64±8.75)U/L]、AST[(80.22±4.71)U/L vs (69.26±5.37)U/L],以及肝组织中ROS[(1 030.21±115.87) pg/mL vs (847.84±63.65) pg/mL]、TNFα[(767.18±60.60) ng/mL vs (698.89±16.99) ng/mL]、IL-1β[(29.97±1.37) ng/mL vs (26.70±3.09) ng/mL]、IL-6[(59.13±7.09) pg/mL vs (49.29±3.41) pg/mL)]均显著降低(P值均<0.05);与control组比较,LPS 组小鼠肝组织切片HE染色显示出肝小叶结构破坏、炎性细胞浸润、细胞间隙模糊、肝细胞肿胀; LPS+SS-31组炎性细胞浸润减少，肝细胞肿胀减轻。结论 线粒体靶向抗氧化剂SS-31可降低ROS水平，下调脓毒症时高表达的炎性因子，减轻小鼠脓毒症相关急性肝损伤。更多还原

【Abstract】 Objective To investigate the effect of the mitochondria-targeted antioxidant SS-31 on acute liver injury in a mouse model of sepsis. Methods A total of 24 adult male C57 BL/6 J mice were randomly divided into control group, control+SS-31 group, lipopolysaccharide(LPS) group, and LPS+SS-31 group, with 6 mice in each group. The mice were given intraperitoneal injection of LPS(10 mg/kg) to establish a model of sepsis and acute liver injury, followed by intraperitoneal injection of SS-31(10 mg/kg) for treatment, and the mice in the control group were given intraperitoneal injection of an equal volume of PBS solution, followed by intraperitoneal injection of an equal volume of normal saline. After 12 hours, ELISA was used to measure the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), superoxide dismutase(SOD), tumor necrosis factor-α(TNFα), interleukin-1β(IL-1β), and interleukin-6(IL-6), and HE staining was used to observe liver histopathological changes. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the LPS group, the LPS+SS-31 group had significant reductions in the serum levels of ALT(140.05±12.22 U/L vs 102.64±8.75 U/L, P<0.05) and AST(80.22±4.71 U/L vs 69.26±5.37 U/L, P<0.05) and the levels of ROS(1 030.21±115.87 pg/mL vs 847.84±63.65 pg/mL, P<0.05), TNFα(767.18±60.60 ng/mL vs 698.89±16.99 ng/mL, P<0.05), IL-1β(29.97±1.37 ng/mL vs 26.70±3.09 ng/mL, P<0.05), and IL-6(59.13±7.09 pg/mL vs 49.29±3.41 pg/mL, P<0.05) in liver tissue. Compared with the control group based on HE staining, the LPS group showed destruction of hepatic lobular structure, inflammatory cell infiltration, ambiguous intercellular space, and hepatocyte swelling, while the LPS+SS-31 group showed alleviation of inflammatory cell infiltration and hepatocyte swelling. Conclusion The mitochondria-targeted antioxidant SS-31 can reduce the production of ROS, downregulate the highly expressed inflammatory factors in sepsis, and alleviate sepsis-related acute liver injury in mice.更多还原