Department of Gastroenterology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, Jiangsu 211900, China.
Department of General Surgery, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, Jiangsu 211900, China.
Biomed Pharmacother. 2024 Sep;178:117301. doi: 10.1016/j.biopha.2024.117301. Epub 2024 Aug 12.
This study aimed to evaluate the therapeutic effects of forsythoside A (FA) on brain injury induced by severe acute pancreatitis (SAP) using a murine model.
Mice were induced with 3.5 % sodium taurocholate to model SAP-induced brain injury (SAP-IBI) and were randomly assigned to four distinct treatment regimens: the SAP-IBI model group (SAP-IBI), low-dose FA treatment group (FA L+SI), middle-dose FA treatment group (FA M+SI), and high-dose FA treatment group (FA H+SI). A sham-operation group (SO) served as a negative control. Serum levels of interleukin-1β (IL-1β) and IL-18 were quantified via ELISA, and serum amylase levels were assessed using optical turbidimetry. mRNA expression levels of AIM2, ASC, Caspase-1, and GAPDH in hippocampal brain tissue were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Protein levels of NLRP3, GSDMD, IL-1β, and IL-18 in hippocampal brain tissue were evaluated using Western blotting. Neurological function in surviving mice was assessed through modified neurological severity scores (mNSS). Transmission electron microscopy (TEM) provided ultrastructural analysis of the hippocampus. Additionally, water content and pathological changes in hippocampal brain tissue were examined 24 hours post-operation, along with other relevant indicators.
At 24 hours post-operation, the FA H+SI group exhibited significantly reduced levels of serum amylase, IL-1β, and IL-18, along with decreased expression of AIM2, ASC, and Caspase-1 mRNA. Furthermore, NLRP3 protein levels, water content, pancreas and hippocampal brain pathological scores, and mNSS were significantly lower compared to the SAP-IBI group (P<0.01).
FA demonstrates protective effects against SAP-IBI in mice, suggesting potential therapeutic benefits.
本研究旨在通过建立小鼠模型评估连翘酯苷 A (FA) 对重症急性胰腺炎 (SAP) 诱导脑损伤 (SAP-IBI) 的治疗作用。
采用 3.5%牛磺胆酸钠诱导小鼠 SAP-IBI 模型，随机分为四组：SAP-IBI 模型组 (SAP-IBI)、低剂量 FA 治疗组 (FA L+SI)、中剂量 FA 治疗组 (FA M+SI) 和高剂量 FA 治疗组 (FA H+SI)。假手术组 (SO) 作为阴性对照。采用酶联免疫吸附试验 (ELISA) 检测血清白细胞介素-1β (IL-1β) 和 IL-18 水平，采用比浊法检测血清淀粉酶水平。采用定量逆转录聚合酶链反应 (qRT-PCR) 检测海马组织中 AIM2、ASC、Caspase-1 和 GAPDH 的 mRNA 表达水平。采用 Western blot 法检测海马组织中 NLRP3、GSDMD、IL-1β 和 IL-18 的蛋白表达水平。采用改良神经功能缺损评分 (mNSS) 评估存活小鼠的神经功能。采用透射电子显微镜 (TEM) 观察海马组织的超微结构。术后 24 小时检测海马组织含水量和病理学变化及其他相关指标。
术后 24 小时，FA H+SI 组血清淀粉酶、IL-1β 和 IL-18 水平显著降低，AIM2、ASC 和 Caspase-1 mRNA 表达降低。与 SAP-IBI 组相比，NLRP3 蛋白水平、水含量、胰腺和海马组织病理评分以及 mNSS 显著降低 (P<0.01)。
FA 对 SAP-IBI 诱导的小鼠具有保护作用，提示其具有潜在的治疗作用。
