隐丹参酮调节Rac1/AKT/NF-κB信号通路对脓毒症大鼠肠损伤的影响

doi:10.3969/j.issn.1006-6233.2024.10.03

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Abstract Objective: To investigate the effect of cryptotanshinone (CRY) on intestinal injury in septic rats by regulating the Ras related C3 botulinum toxin substrate 1 (Racl)/serine threonine protease (AKT)/nuclear factor kappa B (NF-κB) signaling pathway. Methods: Sepsis rat models were established and grouped into control group, model group, high-dose, medium, and low-dose cryptotanshinone groups (7.0mg·kg^-1·d^-1CRY-H group, 14.0mg·kg^-1·d^-1 CRY-M group, 28.0mg·kg^-1·d^-1 CRY-L group), and high-dose cryptotanshinone+NF-κB pathway activator group (28.0mg·kg^-1·d^-1 CRY-H+5.0mg·kg^-1·d^-1 PMA group), with 12 rats in each group. The control group and the model group were treated with the same dose of normal saline once a day for 21 consecutive days. The levels of serum inflammatory factors, oxidative stress and intestinal mucosal barrier indexes in sepsis rats were detected by kit. HE staining was used to observe the pathological morphology of intestinal tissue in rats. The expressions of ZO-1, occludin and pathway proteins in intestinal tissues of rats were detected by immunohistochemistry and Western blotting, respectively. Results: Compared with the control group, the mucosal villi in the model group were disorderly arranged, with some mucosa shedding and necrosis, a large number of inflammatory cells infiltrating, the histopathological score was higher, the serum levels of TNF-α, IL-1β, MDA, endotoxin, and D-lactate increased, the level of SOD decreased, the expression of Rac1, p-AKT/AKT, p-NF-κB/NF-κB was upregulated, while ZO-1 and occludin were downregulated (P<0.05). Compared with the model group, the CRY-L, CRY-M, and CRY-H groups had relatively intact intestinal mucosal villi, inflammatory cell infiltration reduced, and histopathological scores decreased, the serum levels of TNF-α, IL-1β, MDA, endotoxin, and D-lactate decreased, the level of SOD increased, the expression of Rac1, p-AKT/AKT, p-NF-κB/NF-κB was downregulated, while ZO-1 and occludin were upregulated (P<0.05). Compared with the CRY-H group, the CRY-H+PMA group had more inflammatory cell infiltration in intestinal mucosal cells, the histopathological scores increased, the serum levels of TNF-α, IL-1β, MDA, endotoxin, and D-lactate increased, the level of SOD decreased, the expression of Rac1, p-AKT/AKT, p-NF-κB/NF-κB was upregulated, while ZO-1 and occludin were downregulated (P<0.05). Conclusion: Cryptotanshinone inhibits the Rac1/AKT/NF-κB signaling pathway and improves intestinal injury in septic rats.

Key words： Sepsis Cryptotanshinone Ras related C3 botulinum toxin substrate 1/serine threonine protease/nuclear factor kappa B signaling pathway Intestinal injury

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.10.03 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I10/1597

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