Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433 Shanghai, China.
Mediators Inflamm. 2018 May 16;2018:5871431. doi: 10.1155/2018/5871431. eCollection 2018.
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 (HO, O, 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-B 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.
主要表现为氧化应激、炎症和细胞凋亡的脓毒性肝损伤/衰竭导致了终末期肝病理学的很大一部分，而有效的干预措施有限。在这里，我们使用脂多糖 (LPS) 刺激模型来模拟脓毒性肝损伤，并研究了 sophocarpine 对脂多糖诱导的内毒素血症小鼠的影响。我们发现 sophocarpine 提高了小鼠的存活率，并减轻了 LPS 诱导的肝损伤，这表现在病理学和血清肝酶上。进一步的研究发现 sophocarpine 改善了肝氧化应激指标 (HO、O 和 NO)，并增强了抗氧化分子的表达，如超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT) 和谷胱甘肽 (GSH)。此外， sophocarpine 还减轻了局部和系统性炎症，并进一步减少了肝细胞凋亡。本研究还探讨了 sophocarpine 在抑制 CYP2E/Nrf2 通路的表达、抑制 p38/JNK 级联和 NF-B 通路以及抑制 PI3K/AKT 信号通路减少细胞凋亡方面的机制证据。综上所述，本研究揭示了 sophocarpine 通过抑制 CYP2E/Nrf2/ROS 以及 PI3K/AKT 通路在 LPS 刺激的氧化反应、炎症和细胞凋亡中的保护作用，提示其在减轻脓毒性内毒素血症的炎症和肝损伤方面具有广阔的应用前景。
