■脂多糖(LPS)加剧全身性炎症反应并导致过多的液体渗漏。已发现2,4,6-三羟基-3-香叶基苯乙酮(tHGA)在体外可防止LPS诱导的血管炎症和内皮通透性过高。
本研究评估了tHGA对内毒素血症小鼠中LPS诱导的全身性炎症和血管通透性的体内保护作用。
■BALB/c小鼠腹膜内用tHGA预处理1小时,然后进行6小时的LPS诱导。在用2、20和100mg/kgtHGA预处理的小鼠(n=6)中进行伊文思蓝渗透性测定和白细胞迁移测定。tHGA(20、40和80mg/kg)对LPS诱导的血清TNF-α分泌的影响,使用ELISA评估肺功能障碍和致死率(n=6),组织病理学分析(n=6)和生存能力测定(n=10),分别。生理盐水和地塞米松作为阴性对照和药物对照。分别。
■tHGA在2、20和100mg/kg时显着抑制血管通透性,抑制百分比为48%,85%和86%,分别,与LPS对照组相比(IC50=3.964mg/kg)。在20和100mg/kg剂量下抑制白细胞浸润,抑制百分比分别为73%和81%,(IC50=17.56mg/kg)。然而,所有tHGA剂量(20,40和80mg/kg)均不能预防内毒素血症小鼠的致死性,因为tHGA不能抑制TNF-α过度产生和器官功能障碍.
■tHGA可以通过与其他抗炎剂组合而被开发为与不受控制的血管渗漏有关的疾病的潜在治疗剂。
UNASSIGNED: Lipopolysaccharide (LPS) exacerbates systemic inflammatory responses and causes excessive fluid leakage. 2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) has been revealed to protect against LPS-induced vascular inflammation and endothelial hyperpermeability in vitro.
UNASSIGNED: This study assesses the in vivo protective effects of tHGA against LPS-induced systemic inflammation and vascular permeability in endotoxemic mice.
UNASSIGNED: BALB/c mice were intraperitoneally pre-treated with tHGA for 1 h, followed by 6 h of LPS induction. Evans blue permeability assay and leukocyte transmigration assay were performed in mice (n = 6) pre-treated with 2, 20 and 100 mg/kg tHGA. The effects of tHGA (20, 40 and 80 mg/kg) on LPS-induced serum TNF-α secretion, lung dysfunction and lethality were assessed using ELISA (n = 6), histopathological analysis (n = 6) and survivability assay (n = 10), respectively. Saline and dexamethasone were used as the negative control and drug control, respectively.
UNASSIGNED: tHGA significantly inhibited vascular permeability at 2, 20 and 100 mg/kg with percentage of inhibition of 48%, 85% and 86%, respectively, in comparison to the LPS control group (IC50=3.964 mg/kg). Leukocyte infiltration was suppressed at 20 and 100 mg/kg doses with percentage of inhibition of 73% and 81%, respectively (IC50=17.56 mg/kg). However, all tHGA doses (20, 40 and 80 mg/kg) failed to prevent endotoxemic mice from lethality because tHGA could not suppress TNF-α overproduction and organ dysfunction.
UNASSIGNED: tHGA may be developed as a potential therapeutic agent for diseases related to uncontrolled vascular leakage by combining with other anti-inflammatory agents.