CONTEXT Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis. OBJECTIVE We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway. MATERIALS AND METHODS Fifty male BALB/c mice (n = 10 per group) were used to establish a caecal ligation and puncture (CLP) mouse model, and given daily injections of sesamin at a low, middle, or high concentration (25, 50, or 100 μM) during the seven-day study period; survival curves were generated by the Kaplan-Meier method. H&E staining and TUNEL staining were performed to assess changes in intestinal morphology intestinal damage in the mouse intestinal epithelium. Molecules related to the HMGB1/TLR4/IL-33 pathway were assessed by RT-qPCR and Western blotting. RESULTS We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6-7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin. DISCUSSION AND CONCLUSIONS Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury.

中文翻译：

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芝麻素通过 HMGB1/TLR4/IL-33 信号通路减轻脓毒症肠道损伤

背景 脓毒症目前是重症监护病房 (ICU) 的主要死亡原因之一。之前有报道称芝麻素可以抑制炎症。然而，没有研究揭示芝麻素对败血症的影响。目的我们通过HMGB1/TLR4/IL-33信号通路研究芝麻素对脓毒症病理生理的影响机制。材料与方法 50只雄性BALB/c小鼠（每组n=10）建立盲肠结扎穿刺（CLP）小鼠模型，每天注射低、中、高浓度芝麻素（25、50 , 或 100 μM) 在 7 天的研究期间；生存曲线由 Kaplan-Meier 方法生成。进行 H＆E 染色和 TUNEL 染色以评估小鼠肠上皮肠损伤的肠道形态变化。通过 RT-qPCR 和蛋白质印迹评估与 HMGB1/TLR4/IL-33 通路相关的分子。结果我们发现脓毒症组小鼠仅存活4天，而芝麻素组小鼠存活6-7天。此外，芝麻素显着缓解了MPO（21%、33.3%）、MDA（40.5%和31.6%）、DAO（1.24倍和2.31倍）以及促炎细胞因子（如TNF-脓毒症诱导后 24 和 48 小时，α（75% 和 79%）和 IL-6（1 倍和 1.67 倍）下调 HMGB1、TLR4 和 IL-33 的表达，同时上调 ZO-1 和封闭素。讨论与结论芝麻素提高脓毒症小鼠7天存活率，通过HMGB-1/TLR4/IL-33信号通路抑制脓毒症炎症反应，进一步减轻肠道损伤。