Tang Xiao-Mei, Liao Zhi-Kai, Huang You-Wei, Lin Xi, Wu Liang-Cai
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
Asian Pac J Trop Med. 2017 Jun;10(6):582-587. doi: 10.1016/j.apjtm.2017.06.007. Epub 2017 Jun 16.
To investigate whether atractylenolide Ⅰ (ATL-Ⅰ) has protective effect on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in vivo and in vitro, and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ treatment.
New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6 h at a rate of 600 μg/kg (10 mL/h). Similarly, in the treatment groups, 1.0, 2.0, or 5.0 mg/kg ATL-Ⅰ were given. Both survival rate and organ function were tested, including the level of alanine aminotransferase (ALT), blood urine nitrogen (BUN), and TNF-α were examined by ELISA. Also hemostatic and fibrinolytic parameters in serum were measured. RAW 264.7 macrophage cells were administered with control, LPS, LPS + ATL-Ⅰ and ATL-Ⅰ alone, and TNF-α, phosphorylation (P)-IκBα, phosphorylation (P)-NF-κB (P65) and NF-κB (P65) were determined by Western blot.
The administration of LPS resulted in 73.3% mortality rate, and the increase of serum TNF-α, BUN and ALT levels. When ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model, also improved the function of blood coagulation. And protein analysis indicated that ATL-I remarkably protected liver and renal as decreasing TNF-α expression. In vitro, ATL-I obviously decreased LPS-induced TNF-α production and the expression of P-NF-κB (P65), with the decrease of P-IκBα.
ATL-Ⅰ has protective effect on LPS-induced DIC, which can elevate the survival rate, reduce organ damage, improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.
研究白术内酯Ⅰ（ATL-Ⅰ）在体内和体外对脂多糖（LPS）诱导的弥散性血管内凝血（DIC）是否具有保护作用，并探讨NF-κB信号通路是否参与ATL-Ⅰ的治疗作用。
新西兰白兔通过耳缘静脉以600μg/kg（10mL/h）的速率在6小时内注射LPS。同样，在治疗组中，给予1.0、2.0或5.0mg/kg的ATL-Ⅰ。检测存活率和器官功能，包括通过ELISA检测丙氨酸转氨酶（ALT）、血尿素氮（BUN）水平以及TNF-α水平。同时测定血清中的止血和纤溶参数。将RAW 264.7巨噬细胞分别给予对照组、LPS组、LPS + ATL-Ⅰ组和单独的ATL-Ⅰ组，并通过蛋白质免疫印迹法测定TNF-α、磷酸化（P）-IκBα、磷酸化（P）-NF-κB（P65）和NF-κB（P65）。
给予LPS导致死亡率达73.3%，血清TNF-α、BUN和ALT水平升高。当给予ATL-Ⅰ治疗时，显著提高了LPS诱导的DIC模型的存活率，同时改善了凝血功能。蛋白质分析表明，ATL-Ⅰ通过降低TNF-α表达显著保护肝脏和肾脏。在体外，ATL-Ⅰ明显降低LPS诱导的TNF-α产生以及P-NF-κB（P65）的表达，同时P-IκBα降低。
ATL-Ⅰ对LPS诱导的DIC具有保护作用，可提高存活率，减少器官损伤，改善凝血功能，并通过抑制NF-κB信号通路的激活来抑制TNF-α表达。
