Department of Neurosurgery, Shanxi Province People's Hospital, 29 Shuangtasi Street, Taiyuan, 030012, China.
Department of Neurosurgery, Shanxi Coal Mine Hospital, Taiyuan, 030012, China.
Inflammopharmacology. 2019 Aug;27(4):809-816. doi: 10.1007/s10787-018-0503-z. Epub 2018 Jun 26.
The study was conducted to scrutinize the outcome of isoliquiritigenin (ISL) against cerebral injury in septic mice.
The sepsis was introduced using cecal ligation and puncture (CLP) method in experimental mice. The effect of ISL was quantified using the content of brain water and blood brain barrier (BBB) permeability. The effect on the levels of myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in brain homogenates was also determined. The effect of ISL on the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in serum was also estimated. The levels of various inflammatory biomarkers (COX-2 and PGE2) were also studied. The expression of NF-κB signalling cascade and inducible nitric oxide synthase (iNOS) was estimated by Western blot.
Compared with CLP group, the brain water content was found to be reduced significantly together with the enhanced BBB integrity in ISL treated group. The level of MDA was reduced together with enhanced level of SOD and GSH in the ISL treated group. The levels of TNF-α, IL-1β, and IL-6 were also found to be modulated in ISL group. The level of COX-2 and PGE2 was reduced to near normal after ISL administration together with increase in the IκBα expression and reduction of p65 and p-p65 expression in a concentration-dependent manner. The expression of iNOS was also found to be reduced in ISL group.
These results demonstrate that ISL causes protection of CLP-induced sepsis in experimental mice via multiple pathways.
本研究旨在探究异甘草素（ISL）对脓毒症小鼠脑损伤的作用。
采用盲肠结扎穿孔（CLP）法在实验小鼠中诱发脓毒症。通过脑水含量和血脑屏障（BBB）通透性来量化 ISL 的作用。还测定了脑匀浆中髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽（GSH）水平的变化。还估计了 ISL 对血清中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和 IL-6 水平的影响。还研究了各种炎症生物标志物（COX-2 和 PGE2）的水平。通过 Western blot 估计 NF-κB 信号通路和诱导型一氧化氮合酶（iNOS）的表达。
与 CLP 组相比，ISL 治疗组的脑水含量明显降低，BBB 完整性增强。ISL 治疗组 MDA 水平降低，SOD 和 GSH 水平升高。ISL 组 TNF-α、IL-1β 和 IL-6 水平也发生了变化。ISL 给药后 COX-2 和 PGE2 水平降低至接近正常，IκBα 表达增加，p65 和 p-p65 表达减少，呈浓度依赖性。ISL 组 iNOS 的表达也减少。
这些结果表明，ISL 通过多种途径对 CLP 诱导的实验小鼠脓毒症起到保护作用。
