Liensinine attenuates inflammation and oxidative stress in spleen tissue in an LPS-induced mouse sepsis model

Sepsis is a complex syndrome caused by multiple pathogens and involves multiple organ failure, particularly spleen dysfunction. In 2017, the worldwide incidence was 48.9 million sepsis cases and 11 million sepsis-related deaths were reported (Rudd et al., 2020). Inflammation, oxidative stress, and apoptosis are the most common pathologies seen in sepsis. Liensinine (LIE) is a bisbenzylisoquinoline-type alkaloid extracted from the seed embryo of Nelumbo nucifera. Lotus seed hearts have high content of LIE which mainly has antihypertensive and antiarrhythmic pharmacological effects. It can exert anti-carcinogenic activity by regulating cell, inflammation, and apoptosis signaling pathways (Manogaran et al., 2019). However, its protective effect from sepsis-induced spleen damage is unknown. In this research, we established a mouse sepsis model induced by lipopolysaccharide (LPS) and investigated the protective effects of LIE on sepsis spleen injury in terms of inflammatory response, oxidative stress, and apoptosis.本研究基于脂多糖（LPS）诱导的小鼠脓毒症模型，探讨莲心碱（LIE）对脓毒症中脾损伤的潜在保护作用。脓毒症常伴有炎症、氧化应激和细胞凋亡，并将导致身体器官功能障碍，对脾脏损伤尤甚。将30只小鼠随机分为5组（n=6）：对照组、LPS （10 mg/kg）、LIE（10 mg/kg）+LPS、LIE （20 mg/kg）+LPS和LIE （40 mg/kg）+LPS。脾脏损伤通过苏木精–伊红染色（H&E）确定；采用定量聚合酶链反应（qPCR）检测脾脏组织中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-10、IL-1β和一氧化氮合酶（iNOS）的转录水平。同时对包括丙二醛（MDA）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）在内的氧化应激指标进行测定；采用TUNEL法检测细胞凋亡水平。结果显示，LIE可减轻脾脏组织病理学损伤并抑制细胞凋亡，显著降低促炎因子TNF-α、IL-6、IL-1β和iNOS的转录水平，并增加抗炎因子IL-10的表达。此外，LIE预处理后可降低MDA脂质过氧化指标，增强CAT、SOD和GSH-Px的抗氧化活性。综上所述，LIE具有潜在的抗氧化和抗炎能力，可减轻脾脏在脓毒症中的损伤。.