罗汉果皂苷Ⅵ对小鼠脓毒症致急性肝损伤的作用及其机制探讨

doi:10.7499/j.issn.1008-8830.2007088

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目的探讨罗汉果皂苷Ⅵ（MⅥ）对小鼠脓毒症致急性肝损伤的作用及其可能作用机制。方法将60只雄性C57BL/6小鼠随机分成假手术组、模型组、MⅥ低剂量组（低剂量组，25 mg/kg）、MⅥ高剂量组（高剂量组，100 mg/kg）和过氧化物酶增殖激活受体γ辅助激活物1α（PGC-1α）抑制剂组（抑制剂组，100 mg/kg MⅥ+30 mg/kg PGC-1α抑制剂SR-18292），每组12只。采用盲肠结扎穿孔术制备脓毒症小鼠模型，造模成功后开始腹腔注射给药，每天1次，连续3 d。ELISA法检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）浓度；比色法检测肝组织中丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）水平；苏木精-伊红染色观察肝组织病理学变化；检测肝脏线粒体呼吸功能，计算线粒体呼吸控制率；RT-PCR检测肝组织线粒体DNA（mtDNA）的拷贝数及肝组织中PGC-1α、核呼吸因子1（NRF-1）、线粒体转录因子A（TFAM）的mRNA水平；Western blot检测肝组织中PGC-1α、NRF-1和TFAM的蛋白表达水平。结果与假手术组比较，模型组小鼠血清中ALT、AST水平及肝组织中MDA含量显著增加（P < 0.05），肝组织中GSH-Px和SOD活性显著降低（P < 0.05）；肝组织病理学损伤严重；肝组织线粒体呼吸控制率和mtDNA拷贝数，以及肝组织中PGC-1α、NRF-1、TFAM的mRNA及其蛋白表达水平均显著降低（P < 0.05）。与模型组比较，高剂量组小鼠血清中ALT、AST水平及肝组织中MDA含量显著减少（P < 0.05），肝组织中GSH-Px和SOD活性显著增加（P < 0.05）；肝组织病理学损伤得到改善；肝组织线粒体呼吸控制率和mtDNA拷贝数，以及肝组织中PGC-1α、NRF-1、TFAM的mRNA及其蛋白表达水平均显著上升（P < 0.05）；低剂量组上述指标差异均无统计学意义（P > 0.05）。PGC-1α抑制剂SR-18292可显著抑制高剂量MⅥ的干预效果（P < 0.05）。结论 MⅥ能有效减轻小鼠脓毒症致急性肝损伤，其机制可能与增强PGC-1α介导的线粒体生物合成有关。

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	周海银
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	刘萍萍
	肖政辉

关键词 ：脓毒症, 急性肝损伤, 罗汉果皂苷Ⅵ, 线粒体生物合成, 小鼠

Abstract：Objective To study the effect of mogroside VI (MVI) on acute liver injury induced by sepsis in mice and its possible mechanisms. Methods A total of 60 male C57BL/6 mice were randomly divided into five groups:sham-operation, model, low-dose MVI (25 mg/kg), high-dose MVI (100 mg/kg), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) inhibitor (100 mg/kg MVI+30 mg/kg PGC-1α inhibitor SR-18292), with 12 mice in each group. Cecal ligation and puncture were performed to establish a mouse model of sepsis. The drugs were given by intraperitoneal injection after the model was established, once a day for 3 consecutive days. ELISA was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Colorimetry was used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in liver tissue. Hematoxylin-eosin staining was used to observe liver histopathological changes. Liver mitochondrial respiratory function was measured, and mitochondrial respiratory control rate was calculated. RT-PCR was used to measure the copy number of mitochondrial DNA (mtDNA) in liver tissue and the mRNA expression levels of PGC-1α, nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) in liver tissue. Western blot was used to measure the protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue. Results Compared with the sham-operation group, the model group had significant increases in the serum levels of ALT and AST and the content of MDA in liver tissue (P < 0.05) and significant reductions in the activities of GSH-Px and SOD in liver tissue (P < 0.05). The model group had also severe liver histopathological injury and significant reductions in the mitochondrial respiratory control rate, the copy number of mtDNA, and the mRNA and protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue (P < 0.05). Compared with the model group, the high-dose group had significant reductions in the serum levels of ALT and AST and the content of MDA in liver tissue (P < 0.05), significant increases in the activities of GSH-Px and SOD in liver tissue (P < 0.05), significant improvement in liver histopathological injury, and significant increases in the mitochondrial respiratory control rate, the copy number of mtDNA, and the mRNA and protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue (P < 0.05). There were no significant differences in the above indicators between the low-dose and model groups (P > 0.05). The PGC-1α inhibitor SR-18292 significantly inhibited the intervention effect of high-dose MVI (P < 0.05). Conclusions MVI can effectively alleviate acute liver injury caused by sepsis in mice, possibly by enhancing mitochondrial biosynthesis mediated by PGC-1α.

Key words： Sepsis Acute liver injury Mogroside VI Mitochondrial biosynthesis Mice

收稿日期: 2020-07-13

基金资助:湖南省科技创新平台与人才计划（2018TP1028）；2018年度湖南省重点研发计划项目（2018SK2135）。

通讯作者: 肖政辉,女,主任医师,教授。Email:xiaozh888@126.com。 E-mail: xiaozh888@126.com

作者简介: 周海银,女,硕士,副主任医师。

引用本文:

周海银,隆彩霞,罗兰等. 罗汉果皂苷Ⅵ对小鼠脓毒症致急性肝损伤的作用及其机制探讨[J]. 中国当代儿科杂志, 2020, 22(11): 1233-1239.

ZHOU Hai-Yin,LONG Cai-Xia,LUO Lan et al. Effect of mogroside VI on acute liver injury induced by sepsis in mice and related mechanisms[J]. CJCP, 2020, 22(11): 1233-1239.

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http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2007088 或 http://www.zgddek.com/CN/Y2020/V22/I11/1233

[1]	Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets[J]. Int J Mol Sci, 2019, 20(21):5376.
[2]	Woźnica EA, Inglot M, Woźnica RK, et al. Liver dysfunction in sepsis[J]. Adv Clin Exp Med, 2018, 27(4):547-551.
[3]	赵广明, 胡占升. 脓毒症肝损伤的发病机制与治疗研究进展[J]. 解放军医学杂志, 2019, 44(6):515-520.
[4]	Niu B, Ke CQ, Li BH, et al. Cucurbitane glucosides from the crude extract of Siraitia grosvenorii with moderate effects on PGC-1α promoter activity[J]. J Nat Prod, 2017, 80(5):1428-1435.
[5]	Cheng CF, Ku HC, Lin H. PGC-1α as a pivotal factor in lipid and metabolic regulation[J]. Int J Mol Sci, 2018, 19(11):3447.
[6]	Takahashi W, Watanabe E, Fujimura L, et al. Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis[J]. Crit Care, 2013, 17(4):R160.
[7]	闫梦莹, 王妍妍, 毛幸, 等. 脓毒症小鼠肝损伤时FUNDC1/LC3Ⅱ信号通路的变化[J]. 中华麻醉学杂志, 2018, 38(6):736-738.
[8]	Xing W, Yang L, Peng Y, et al. Ginsenoside Rg3 attenuates sepsis-induced injury and mitochondrial dysfunction in liver via AMPK-mediated autophagy flux[J]. Biosci Rep, 2017, 37(4):BSR20170934.
[9]	王洪雨, 宋学敏, 张宗泽, 等. 脓毒症小鼠肝损伤时胆碱能抗炎通路与自噬的关系[J]. 中华麻醉学杂志, 2019, 39(2):239-242.
[10]	Kingir ZB, Özdemir Kural ZN, Cam ME, et al. Effects of dapagliflozin in experimental sepsis model in rats[J]. Ulus Travma Acil Cerrahi Derg, 2019, 25(3):213-221.
[11]	Bacanlı M, Aydın S, Taner G, et al. Does rosmarinic acid treatment have protective role against sepsis-induced oxidative damage in Wistar Albino rats?[J]. Hum Exp Toxicol, 2016, 35(8):877-886.
[12]	Harrington JS, Choi AMK, Nakahira K. Mitochondrial DNA in sepsis[J]. Curr Opin Crit Care, 2017, 23(4):284-290.
[13]	Zuo Y, Dang R, Peng H, et al. LL-37 exacerbates local inflammation in sepsis-induced acute lung injury by preventing mitochondrial DNA (mtDNA) degradation-induced autophagy[J]. Med Sci Monit, 2019, 25:6193-6203.
[14]	张媛媛, 董艾莉, 王妍妍, 等. 氢对脓毒症小鼠心肌线粒体Drp1表达的影响[J]. 中华麻醉学杂志, 2017, 37(9):1136-1138.
[15]	Lu P, Hogan-Cann AD, Kamboj A, et al. Poly(ADP-ribose) polymerase-1 inhibits mitochondrial respiration by suppressing PGC-1α activity in neurons[J]. Neuropharmacology, 2019, 160:107755.