背景:脓毒症是导致肠功能障碍的器官功能损伤或衰竭的重要原因。大黄素(Emo)因其显着的抗炎和抗菌特性而受到广泛关注。我们旨在探讨Emo在脓毒症中的作用。
方法:SpragueDawley(SD)大鼠用20或40mg/kg的Emo预处理,采用盲肠结扎穿孔法建立脓毒症模型。此后,血糖水平,生化参数,和炎性细胞因子进行测量。此外,还测量了回肠髓过氧化物酶(MPO)活性。血浆二胺氧化酶(DAO)水平,血清中异硫氰酸荧光素-葡聚糖40(FD-40)水平,血液和腹膜液中的细菌数量,回肠组织病理学改变,检测回肠中紧密连接(TJ)蛋白的表达,以评估屏障功能。此外,通过流式细胞术评估CD4+和CD8+T细胞百分比。最后,大鼠存活率计算为活大鼠除以大鼠总数。
结果:Emo预处理不仅降低了血糖水平,但也下调甘油三酯(TG),丙氨酸氨基转移酶(ALT),天冬氨酸转氨酶(AST),血清肌酐(SCr),脓毒症大鼠血尿素氮(BUN)含量,特别是高剂量的Emo(p<0.05)。此外,Emo抑制MPO活性和炎症因子释放(p<0.05)。至关重要的是,在Emo管理之后,回肠屏障功能增强,减少的DAO证明了这一点,FD-40水平,细菌数量减少,回肠病理损伤减轻,TJ蛋白表达增加(p<0.05)。用Emo处理的大鼠表现出CD8+和CD4+T细胞的百分比增加(p<0.05),以及提高存活率。
结论:Emo通过恢复肠功能障碍和提高生存率表现出明显的减轻脓毒症的能力,其机制与抗炎特性密切相关,这为使用Emo治疗脓毒症提供了新的确凿证据。
Sepsis is a significant contributor to organ function damage or failure that results in intestinal dysfunction. Emodin (Emo) has received much attention for its notable anti-inflammatory and antibacterial properties. We aimed to explore the function of Emo on sepsis.
Sprague Dawley (SD) rats were pretreated with 20 or 40 mg/kg of Emo, followed by using cecal ligation and perforation to establish sepsis models. Hereafter, blood glucose levels, biochemical parameters, and inflammatory cytokines were measured. Additionally, ileal myeloperoxidase (MPO) activity was also measured. Diamine oxidase (DAO) level in plasma, fluorescein isothiocyanate-dextran 40 (FD-40) level in serum, bacteria number in blood and peritoneal fluid, histopathological changes of ileum, and tight junction (TJ) protein expressions in ileum were tested to evaluate the barrier function. Furthermore, CD4+ and CD8+ T cells\' percentages were evaluated by flow cytometry. Finally, rats\' survival rate was calculated as live rats divided by the total number of rats.
Emo pretreatment not only decreased blood glucose level, but also downregulated triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), blood urea nitrogen (BUN) contents for sepsis rats, especially for the high dose of Emo (p < .05). Furthermore, Emo inhibited MPO activity and inflammatory factor release (p < .05). Crucially, after Emo administration, the barrier function of ileum was enhanced, evidenced by the reduced DAO, FD-40 levels, decreased bacteria number, alleviated pathological damage in ileum and increased TJ protein expressions (p < .05). Rats treated with Emo exhibited increased percentages of CD8+ and CD4+ T cells (p < .05), as well as an improved survival rate.
Emo exhibited a remarkable ability to attenuate sepsis by restoring intestinal dysfunction and improving survival rates, and the mechanism was closely related to anti-inflammatory properties, which provided new solid evidence for the use of Emo in treating sepsis.