Sesamin attenuates intestinal injury in sepsis via the HMGB1/TLR4/IL-33 signalling pathway

芝麻素通过 HMGB1/TLR4/IL-33 信号通路减轻脓毒症肠道损伤

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作者:Zhi-Ling Li, Min Gao, Ming-Shi Yang, Xue-Fei Xiao, Jing-Jing Liu, Bing-Chang Yang

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.

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.

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

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.

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