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大黄素通过抗炎作用保护大鼠脓毒症性腹膜炎模型的肠道功能并提高其存活率。

Emodin protects against intestinal dysfunction and enhances survival in rat model of septic peritonitis through anti-inflammatory actions.

机构信息

Department of Emergency Medicine, The First People's Hospital of Pinghu, Pinghu, Zhejiang, China.

出版信息

Immun Inflamm Dis. 2023 Aug;11(8):e942. doi: 10.1002/iid3.942.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

脓毒症是导致器官功能损伤或衰竭从而导致肠道功能障碍的主要原因。大黄素(Emo)因其显著的抗炎和抗菌特性而备受关注。我们旨在探讨 Emo 对脓毒症的作用。

方法

Sprague Dawley(SD)大鼠用 20 或 40mg/kg 的 Emo 预处理,然后用盲肠结扎穿孔术建立脓毒症模型。此后,测量血糖水平、生化参数和炎症细胞因子。此外,还测量回肠髓过氧化物酶(MPO)活性。检测血浆中二胺氧化酶(DAO)水平、血清荧光素异硫氰酸酯-葡聚糖 40(FD-40)水平、血液和腹腔液中的细菌数、回肠的组织病理学变化以及回肠中的紧密连接(TJ)蛋白表达,以评估屏障功能。此外,通过流式细胞术评估 CD4+和 CD8+T 细胞的百分比。最后,通过存活大鼠数除以大鼠总数来计算大鼠的存活率。

结果

Emo 预处理不仅降低了血糖水平,还降低了脓毒症大鼠的甘油三酯(TG)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血清肌酐(SCr)、血尿素氮(BUN)含量,尤其是高剂量的 Emo(p<.05)。此外,Emo 抑制了 MPO 活性和炎症因子的释放(p<.05)。至关重要的是,Emo 给药后,回肠的屏障功能得到增强,表现为 DAO、FD-40 水平降低,细菌数量减少,回肠病理损伤减轻,TJ 蛋白表达增加(p<.05)。Emo 治疗的大鼠 CD8+和 CD4+T 细胞的百分比增加(p<.05),且存活率提高。

结论

Emo 通过恢复肠道功能障碍和提高存活率来显著减轻脓毒症,其机制与抗炎特性密切相关,为 Emo 治疗脓毒症提供了新的有力证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff16/10461418/8e587fb7aeb5/IID3-11-e942-g006.jpg

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