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以(-)-假半枝莲碱为主要成分,通过调节HMGB1和IL-22减轻重症急性胰腺炎介导的急性肺损伤

, with (-)-Pseudosemiglabrin as the Major Constituent, Alleviates Severe Acute Pancreatitis-Mediated Acute Lung Injury by Modulating HMGB1 and IL-22.

作者信息

Soliman Gamal A, Alamri Mohammed A, Abdel-Rahman Rehab F, Elbaset Marawan A, Ogaly Hanan A, Abdel-Kader Maged S

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.

Department of Pharmacology, National Research Centre, Giza 12622, Egypt.

出版信息

Int J Mol Sci. 2025 Mar 13;26(6):2572. doi: 10.3390/ijms26062572.

DOI:10.3390/ijms26062572
PMID:40141214
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11942157/
Abstract

Ischemia-reperfusion (IR) injury is a major cause of multiple organ failure. The purpose of this study was to look into the role of (TEP) and its active constituent pseudosemiglabrin (PS) in alleviating severe acute pancreatitis and its associated acute lung injury. We established a rat pancreatic IR model, and the rats were treated with TEP (200 mg/kg and 400 mg/kg) and PS (20 and 40 mg/kg), in addition to the IR control and sham groups. The results showed that the respiratory parameters, including inspiratory time (Ti), expiratory time (Te), duration (Dr), and respiratory rate (RR), were comparable among all groups, while peak inspiratory flow (PIF), forced vital capacity (FVC), and forced expiratory volume at 0.1 s (FEV.) were significantly impaired. Notably, PS at 40 mg/kg showed normal PIF, FVC, and FEV./FVC compared to the IR group, indicating an improved lung function. Additionally, TEP and PS showed protective effects on pancreatic and lung tissues compared to the IR control group, with the following effects: alleviating pathological damage; reducing serum levels of trypsinogen activation peptide (TAP), lipase, and amylase; decreasing oxidative stress markers such as MDA and MPO; restoring antioxidant enzyme activity (GPx); suppressing inflammatory markers TNF-α, IL-6, and NF-κB; downregulating HMGB1 gene in pancreatic tissue; and upregulating the IL-22 gene in lung tissues. In conclusion, the obtained findings demonstrate that oral supplementation of TEP and PS to rats with pancreatic IR alleviates pancreatic and lung injuries by reducing oxidative stress and modulating inflammatory processes, which offers an attractive therapeutic option for severe acute pancreatitis and its associated acute lung injury.

摘要

缺血再灌注(IR)损伤是多器官功能衰竭的主要原因。本研究旨在探讨(TEP)及其活性成分假光萼苔素(PS)在减轻重症急性胰腺炎及其相关急性肺损伤中的作用。我们建立了大鼠胰腺IR模型,除IR对照组和假手术组外,大鼠分别用TEP(200mg/kg和400mg/kg)和PS(20mg/kg和40mg/kg)进行治疗。结果显示,所有组的呼吸参数,包括吸气时间(Ti)、呼气时间(Te)、持续时间(Dr)和呼吸频率(RR)相当,而吸气峰值流速(PIF)、用力肺活量(FVC)和0.1秒用力呼气量(FEV.)均显著受损。值得注意的是,与IR组相比,40mg/kg的PS显示出正常的PIF、FVC和FEV./FVC,表明肺功能有所改善。此外,与IR对照组相比,TEP和PS对胰腺和肺组织具有保护作用,具体表现为:减轻病理损伤;降低血清胰蛋白酶原激活肽(TAP)、脂肪酶和淀粉酶水平;降低氧化应激标志物如丙二醛(MDA)和髓过氧化物酶(MPO);恢复抗氧化酶活性(GPx);抑制炎症标志物肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和核因子-κB(NF-κB);下调胰腺组织中高迁移率族蛋白B1(HMGB1)基因;上调肺组织中白细胞介素-22(IL-22)基因。总之,所得结果表明,给胰腺IR大鼠口服补充TEP和PS可通过降低氧化应激和调节炎症过程减轻胰腺和肺损伤,这为重症急性胰腺炎及其相关急性肺损伤提供了一种有吸引力的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08de/11942157/60fc79327c4c/ijms-26-02572-g007.jpg
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