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影响

满明银; 李娜娜; 卜月; 于凯江

doi:10.3969/j.issn.1001-5256.2022.02.025

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影响

DOI: 10.3969/j.issn.1001-5256.2022.02.025

哈尔滨医科大学附属第一医院重症医学科，哈尔滨 150000

基金项目:

国家自然科学基金 (81770276)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。

作者贡献声明：满明银负责课题设计，资料分析，撰写论文；李娜娜参与收集数据，修改论文；卜月负责实验及修改论文；于凯江负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
于凯江，drkaijiang@163.com

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出版历程
- 收稿日期: 2021-06-10
- 录用日期: 2021-08-26
- 出版日期: 2022-02-20

Influence of mitochondria-targeted antioxidant SS-31 on acute liver injury in a mouse model of sepsis

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150000, China

Research funding:

National Natural Science Foundation of China (81770276)

More Information

Corresponding author: YU Kaijiang, drkaijiang@163.com

摘要

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。
- 肝疾病 /
- 抗氧化剂 /
- 脓毒症 /
- 小鼠，近交C57BL
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 C57BL/6J 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.
- Liver Diseases /
- Antioxidants /
- Sepsis /
- Mice, Inbred C57BL

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图 1 肝组织病理切片(HE染色，×400)

注：a，control组；b，control+SS-31组；c，LPS组；d，LPS+SS-31组。

下载: 全尺寸图片幻灯片

表 1 4组小鼠各指标比较

项目	control组 (n=6)	control+SS-31组 (n=6)	LPS组 (n=6)	LPS+SS-31组 (n=6)	F值	P值
体质量(g)	20.83±1.68	21.03±1.35	21.53±1.36	20.93±1.37	0.275	0.843
血清指标
ALT(U/L)	73.76±4.72	74.67±8.88	140.05±12.22¹⁾	102.64±8.75²⁾³⁾	71.428	＜0.001
AST(U/L)	50.66±1.99	48.75±4.28	80.22±4.71¹⁾	69.26±5.37²⁾³⁾	75.073	＜0.001
氧化应激指标
ROS(pg/mL)	704.13±60.08	660.39±84.44	1 030.21±115.87¹⁾	847.84±63.65²⁾³⁾	23.679	＜0.001
SOD(pg/mL)	761.84±36.36	736.56±31.15	638.72±22.20¹⁾	615.00±46.22²⁾	25.305	＜0.001
炎性指标
TNFα(ng/mL)	618.69±56.28	618.95±59.52	767.18±60.60¹⁾	698.89±16.99²⁾³⁾	11.526	＜0.001
IL-1β(ng/mL)	23.34±1.05	23.24±0.96	29.97±1.37¹⁾	26.70±3.09²⁾³⁾	18.253	0.001
IL-6(pg/mL)	43.19±7.79	42.96±5.56	59.13±7.09¹⁾	49.29±3.41²⁾³⁾	8.985	0.001
注：与control组比较，1)P＜0.05；与control+SS-31组比较，2)P＜0.05；与LPS组比较，3)P＜0.05。

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