Department of Emergency, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1592-1599. doi: 10.26355/eurrev_202102_24869.
The aim of this study was to explore the role of alprostadil (Alp) in cecal ligation and puncture (CLP)-induced septic injury in rats and its possible mechanism of action.
Wistar rats were randomly assigned into three groups, including: Sham group (no CLP was performed), CLP group (CLP was conducted) and Alp group (Alp was injected after CLP). Serum liver function markers, pathological changes in liver tissues, alterations in the level of oxidative stress, activity of the Toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, and release of inflammatory factor tumor necrosis factor alpha (TNF-α) in the liver tissue homogenate were detected in each group.
Compared with Sham group, the rats in CLP group had substantially elevated content of serum liver function markers, increased apoptotic liver cells, upregulated levels of oxidative stress, enhanced activity of the TLR4/NF-κB pathway, and increased release of TNF-α (p<0.05). Meanwhile, there were evident pathological changes under microscopic examination in CLP group compared with Sham group (p<0.05). In comparison with CLP group, Alp group exhibited significantly decreased concentrations of liver function markers, microscopic findings, such as decreased inflammatory cell infiltration in the interstitum, notably lowered proportion of apoptotic cells, decreased level of oxidative stress, weakened activity of the TLR4/NF-κB pathway and restrained release of TNF-α (p<0.05). Furthermore, normal morphology of liver cells was observed in Alp group compared with CLP group (p<0.05).
Alp alleviates liver injury in septic rats by inhibiting the TLR4/NF-κB pathway.
本研究旨在探讨前列地尔（Alp）在盲肠结扎穿刺（CLP）诱导的大鼠脓毒症损伤中的作用及其可能的作用机制。
将 Wistar 大鼠随机分为三组，包括：假手术组（未行 CLP）、CLP 组（行 CLP）和 Alp 组（CLP 后注射 Alp）。检测各组血清肝功能标志物、肝组织病理变化、氧化应激水平变化、Toll 样受体 4（TLR4）/核因子 kappa-轻链增强子的活性 B 细胞（NF-κB）途径和肝组织匀浆中炎症因子肿瘤坏死因子-α（TNF-α）的释放。
与假手术组相比，CLP 组大鼠血清肝功能标志物含量明显升高，凋亡肝细胞增多，氧化应激水平升高，TLR4/NF-κB 途径活性增强，TNF-α释放增加（p<0.05）。同时，CLP 组较假手术组显微镜下观察有明显的病理变化（p<0.05）。与 CLP 组相比，Alp 组肝功能标志物浓度明显降低，间质炎症细胞浸润减少，凋亡细胞比例明显降低，氧化应激水平降低，TLR4/NF-κB 途径活性减弱，TNF-α释放受到抑制（p<0.05）。此外，Alp 组与 CLP 组相比，肝细胞形态正常（p<0.05）。
Alp 通过抑制 TLR4/NF-κB 途径减轻脓毒症大鼠的肝损伤。
