Sophocarpine Attenuates LPS-Induced Liver Injury and Improves Survival of Mice through Suppressing Oxidative Stress, Inflammation, and Apoptosis.
Sophocarpine Attenuates LPS-Induced Liver Injury and Improves Survival of Mice through Suppressing Oxidative Stress, Inflammation, and Apoptosis.
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槐果碱通过抑制氧化应激、炎症和细胞凋亡来减轻 LPS 引起的肝损伤并提高小鼠的存活率
DOI：
10.1155/2018/5871431
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发表时间：
2018
影响因子：
4.6
通讯作者：
Deng X
中科院分区：
文献类型：
--
作者：
Jiang Z;Meng Y;Bo L;Wang C;Bian J;Deng X
脓毒性肝损伤/衰竭主要以氧化应激、炎症和细胞凋亡为特征，导致大部分终末期肝脏病理，有效干预有限。本研究采用脂多糖（LPS）刺激模型模拟脓毒性肝损伤，观察槐果碱对LPS刺激的内毒素血症小鼠的影响。病理学和血清肝酶结果表明槐果碱能提高小鼠的存活率，减轻LPS诱导的肝损伤。进一步的研究发现，槐果碱改善肝脏氧化应激指标（H2 O2，O2-和NO），并增强抗氧化分子如超氧化物歧化酶（SOD），过氧化氢酶（CAT）和谷胱甘肽（GSH）的表达。此外，槐果碱还减轻局部和全身炎症，并进一步减少肝细胞凋亡。槐果碱抑制氧化应激时肝脏CYP 2 E/Nrf 2通路的表达，使p38/JNK级联和NF-κB通路失活，同时抑制PI 3 K/AKT信号通路，减少细胞凋亡。结论：槐果碱通过抑制CYP 2 E/Nrf 2/ROS和PI 3 K/AKT通路，对LPS诱导的氧化反应、炎症反应和细胞凋亡具有保护作用，提示槐果碱在减轻脓毒性内毒素血症炎症和肝损伤中具有重要作用。
Septic liver injury/failure that is mainly characterized by oxidative stress, inflammation, and apoptosis led to a great part of terminal liver pathology with limited effective intervention. Here, we used a lipopolysaccharide (LPS) stimulation model to simulate the septic liver injury and investigated the effect of sophocarpine on LPS-stimulated mice with endotoxemia. We found that sophocarpine increases the survival rate of mice and attenuates the LPS-induced liver injury, which is indicated by pathology and serum liver enzymes. Further research found that sophocarpine ameliorated hepatic oxidative stress indicators (H2O2, O2∙−, and NO) and enhanced the expression of antioxidant molecules such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). In addition, sophocarpine also attenuated regional and systematic inflammation and further reduced apoptosis of hepatocytes. Mechanistic evidence was also investigated in the present study as sophocarpine inhibited hepatic expression of the CYP2E/Nrf2 pathway during oxidative stress, inactivated p38/JNK cascade and NF-κB pathway, and, meanwhile, suppressed PI3K/AKT signaling that reduced apoptosis. Conclusively, the present study unveiled the protective role of sophocarpine in LPS-stimulated oxidative reaction, inflammation, and apoptosis by suppressing the CYP2E/Nrf2/ROS as well as PI3K/AKT pathways, suggesting its promising role in attenuating inflammation and liver injury of septic endotoxemia.
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影响因子：
11.1
作者：
Dan C;Jinjun B;Zi-Chun H;Lin M;Wei C;Xu Z;Ri Z;Shun C;Wen-Zhu S;Qing-Cai J;Wu Y
通讯作者：
Wu Y
影响因子：
29
作者：
Baker RG;Hayden MS;Ghosh S
通讯作者：
Ghosh S
DOI：
10.1073/pnas.1531903100
发表时间：
2003-07-22
影响因子：
11.1
作者：
Kiecolt-Glaser, JK;Preacher, KJ;Glaser, R
通讯作者：
Glaser, R
影响因子：
3.2
作者：
Gao, Yonglin;Jiang, Wanglin;Shen, Jingyu
通讯作者：
Shen, Jingyu
影响因子：
2
作者：
Guo, B;Li, C;Xu, F
通讯作者：
Xu, F