和厚朴酚通过激活SIRT1/FOXO1信号通路抵抗小鼠脓毒症脑损伤

Honokiol Alleviates Brain Injury in Septic Mice through Activating SIRT1/FOXO1 Signaling

目的:探究和厚朴酚是否通过激活SIRT1/FOXO1信号通路抵抗小鼠脓毒症脑损伤。方法:通过C57BL/6小鼠盲肠结扎穿孔法建立脓毒症脑损伤模型。小鼠随机分为以下6组:假手术(Sham)组;和厚朴酚处理(HKL)组;盲肠结扎穿孔(CLP)组;盲肠结扎穿孔+和厚朴酚处理(CLP+HKL)组;EX527 (SIRT1特异性抑制剂)预处理+盲肠结扎穿孔+和厚朴酚处理(CLP+HKL+EX527)组;EX527预处理+盲肠结扎穿孔(CLP+EX527)组。盲肠结扎穿孔48 h后检测脑组织内水含量、凋亡率及凋亡相关蛋白Bax、Bcl-2和cleaved Caspase-3的表达情况、炎症相关分子IL-1β与TNF-α、SIRT1信号通路相关蛋白表达情况。结果:与CLP组相比,CLP+HKL组脑组织内SIRT1的表达量及活性、Bcl-2表达量明显增加,而脑组织水含量、凋亡率、Bax、cleaved Caspase-3、IL-1β与TNF-α的表达量明显降低(均P <0.05)。EX527可明显抑制HKL的上述脑保护作用(P <0.05)。结论:和厚朴酚主要通过激活SIRT1/FOXO1信号通路,抑制凋亡与炎症,从而缓解脓毒症脑损伤。

Objective: To elucidate the definite role of silent information regulator 1(SIRT1)/Forkhead box protein O1(FOXO1)signaling pathway in the protective effects of honokiol(HKL) against brain injury in septic mice. Methods: Adult C57 BL/6 mice were subjected to cecal ligation and puncture(CLP) to induce sepsis-associated encephalopathy. The mice were randomly divided into six groups: Sham group, HKL group, CLP group, CLP+HKL group, CLP+HKL+EX527(a selective SIRT1 inhibitor) group and CLP+EX527 group. Forty-eight hours after the surgery, the brain water content, apoptotic ratio and the expression levels of SIRT1,Ac-FOXO1, Bax, Bcl-2, cleaved Caspase-3, IL-1β and TNF-α in each group were measured. Results: Compared with the CLP group,HKL significantly increased the expression level and the deacetylase activity of SIRT1 and the expression level of Bcl-2. HKL reduced brain water content, apoptotic ratio and the expression levels of Bax, cleaved Caspase-3, IL-1β and TNF-α when compared with the CLP group. However, these cerebral-protective effects of honokiol were largely abolished by EX527. Conclusions: HKL attenuates sepsis-associated encephalopathy by reducing apoptosis and inflammation through the activation of SIRT1/FOXO1 signaling pathway.