Department of Pharmacology, Medical College, Jinan University, Guangdong, China.
The 6th Affiliated Hospital, Sun Yat-sen University, Guangdong, China.
Drug Dev Res. 2020 Jun;81(4):517-525. doi: 10.1002/ddr.21647. Epub 2020 Feb 17.
Lipopolysaccharide (LPS) is a toxic component of the outer membrane of gram-negative bacteria that can activate the blood coagulation system, leading to disseminated intravascular coagulation (DIC). DIC is a syndrome characterized by thromboembolism and multiple organ failure. Herein, the beneficial effect of paeoniflorin (PF) on the alleviation of LPS-induced DIC was investigated with an experimental DIC mouse model. Briefly, mice were randomly divided into the following six groups: (1) control; (2) LPS; (3) heparin; (4) low-PF treatment; (5) medium-PF treatment; and (6) high-PF treatment. The histological morphology of the liver and kidney was observed, and the coagulation indicators (such as prothrombin time), function indicators (such as alanine transferase), and inflammatory factors (such as TNF-α) were detected. Additionally, an in vitro cell inflammation model using RAW 264.7 murine macrophages was established. Activation of the nuclear factor kappa B (NF-κB) signaling pathway and tumor necrosis factor-α (TNF-α) were determined by western blotting. Based on our findings, PF could significantly improve the histological morphology of the liver and kidney, indicating that PF protects the liver and kidney against damage induced by LPS. Additionally, PF improved the function and coagulation indicators and reduced the production of inflammatory factors. In vitro, PF inhibited the expression of TNF-α by suppressing NF-κB signaling pathway activation. Collectively, our findings support the hypothesis that PF has anti-inflammatory and anticoagulation effects for the alleviation of LPS-induced DIC. PF is thus a potential co-treatment option for DIC.
脂多糖(LPS)是革兰氏阴性菌外膜的一种有毒成分,能够激活血液凝固系统,导致弥散性血管内凝血(DIC)。DIC 是一种以血栓栓塞和多器官功能衰竭为特征的综合征。在此,通过实验性 DIC 小鼠模型研究了芍药苷(PF)对缓解 LPS 诱导的 DIC 的有益作用。简要地,将小鼠随机分为以下六组:(1)对照组;(2)LPS 组;(3)肝素组;(4)低 PF 治疗组;(5)中 PF 治疗组;和(6)高 PF 治疗组。观察肝和肾的组织形态学,并检测凝血指标(如凝血酶原时间)、功能指标(如丙氨酸转移酶)和炎症因子(如 TNF-α)。此外,建立了 RAW 264.7 小鼠巨噬细胞体外细胞炎症模型。通过 Western blot 测定核因子 kappa B(NF-κB)信号通路和肿瘤坏死因子-α(TNF-α)的激活。基于我们的发现,PF 可以显著改善肝和肾的组织形态学,表明 PF 可保护肝和肾免受 LPS 诱导的损伤。此外,PF 改善了功能和凝血指标,并减少了炎症因子的产生。在体外,PF 通过抑制 NF-κB 信号通路的激活来抑制 TNF-α的表达。总之,我们的研究结果支持 PF 通过抗炎和抗凝作用缓解 LPS 诱导的 DIC 的假说。因此,PF 是 DIC 的一种潜在联合治疗选择。