Abdelnaser Mahmoud, Attya Mina Ezzat, El-Rehany Mahmoud A, Fathy Moustafa
Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia, 61111, Egypt.
Department of Pathology, Faculty of Medicine, Minia University, Minia, 61519, Egypt.
Eur J Med Res. 2025 Aug 6;30(1):715. doi: 10.1186/s40001-025-02982-w.
Nearly 48 million people have sepsis every year, and 11 million lose their lives as a direct consequence of the disease. In addition, sepsis is still the fifth leading death cause globally. The objective of this research was to find out whether pretreatment with Clemastine (CLM) would prevent septic liver damage.
Sepsis induction was established via CLP in male Wister rats. Histopathological analysis and hepatic function panel were assessed. The colorimetric method was used to assess hepatic contents of MDA, GSH, and SOD. ELISA was utilized to evaluate the hepatic TNF-α, IL-18, and IL-1β. qRT-PCR was utilized to evaluate caspase-3, Bax, Bcl-2, and NF-kB mRNA levels. Western blotting assessed NLRP-3, caspase-1, and GSDMD c-NT proteins.
CLP induced hepatic dysfunction, ALT and AST elevation, increased oxidative stress parameters, and escalated hepatic levels of TNF-α, IL-18, and IL-1β. It also augmented NLRP-3, caspase-1, and GSDMD c-NT protein levels, elevated Bax, NF-κB, and caspase-3 mRNA levels, and concurrently inhibited Bcl-2 mRNA levels. Conversely, CLM significantly mitigated molecular, biochemical, and histological changes induced by sepsis. CLM decreased proinflammatory signals, suppressed the production of NLRP-3, caspase-1, and GSDMD c-NT proteins, repressed caspase-3, Bax, and NF-κB, mRNA expression, and enhanced Bcl-2 mRNA expression.
Finally, by suppressing the NLRP-3/Caspase-1 mediated pyroptotic cell death in rats, CLM pretreatment provided protection against septic-liver damage.
每年有近4800万人患脓毒症，其中1100万人直接死于该疾病。此外，脓毒症仍是全球第五大死亡原因。本研究的目的是探究氯马斯汀（CLM）预处理是否能预防脓毒症性肝损伤。
通过盲肠结扎穿孔术（CLP）在雄性Wistar大鼠中诱导脓毒症。评估组织病理学分析和肝功能指标。采用比色法评估肝脏中丙二醛（MDA）、谷胱甘肽（GSH）和超氧化物歧化酶（SOD）的含量。利用酶联免疫吸附测定（ELISA）评估肝脏肿瘤坏死因子-α（TNF-α）、白细胞介素-18（IL-18）和白细胞介素-1β（IL-1β）。采用实时荧光定量聚合酶链反应（qRT-PCR）评估半胱天冬酶-3（caspase-3）、凋亡蛋白 Bax、凋亡蛋白Bcl-2和核因子-κB（NF-κB）的信使核糖核酸（mRNA）水平。蛋白质免疫印迹法检测NLRP-3、半胱天冬酶-1（caspase-1）和Gasdermin D（GSDMD）切割片段（c-NT）蛋白。
CLP诱导肝功能障碍、谷丙转氨酶（ALT）和谷草转氨酶（AST）升高，增加氧化应激参数，并使肝脏中TNF-α、IL-18和IL-1β水平升高。它还增加了NLRP-3、caspase-1和GSDMD c-NT蛋白水平，提高了Bax、NF-κB和caspase-3的mRNA水平，同时抑制了Bcl-2的mRNA水平。相反，CLM显著减轻了脓毒症诱导的分子、生化和组织学变化。CLM降低促炎信号，抑制NLRP-3、caspase-1和GSDMD c-NT蛋白的产生，抑制caspase-3、Bax和NF-κB的mRNA表达，并增强Bcl-2的mRNA表达。
最后，通过抑制大鼠中NLRP-3/半胱天冬酶-1介导的焦亡细胞死亡，CLM预处理对脓毒症性肝损伤起到保护作用。
