Clinical Research Center, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
Department of General Surgery (Hepatopancreatobiliary Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, China.
Phytother Res. 2023 Jan;37(1):181-194. doi: 10.1002/ptr.7605. Epub 2022 Sep 12.
Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and transplantation. Pinocembrin (PIN) is a kind of flavonoid monomer extracted from the local traditional Chinese medicine Penthorum chinense Pursh (P. chinense). However, the effect of PIN on HIRI has not determined. We investigated the protective effect and potential mechanism of PIN against HIRI. Model mice were subjected to partial liver ischemia for 60 min, experimental mice were pretreated with PIN orally for 7 days, and H O -induced oxidative damage model in AML12 hepatic cells was established in vitro. Histopathologic analysis and serum biochemical levels revealed that PIN had hepatoprotective activities against HIRI. The variation of GSH, SOD, MDA, and ROS levels indicated that PIN treatments attenuated oxidative stress in tissue. PIN pretreatment obviously ameliorated apoptosis, and restrained the expression of HMGB1 and TLR4 in vivo. In vitro, compared with H O group, the contents of ROS, mitochondrial membrane potential, apoptotic cells, and Bcl-2 protein were decreased, while the Bax protein expression was increased. Moreover, HMGB-1 small interfering RNA test and western blotting showed that PIN pretreatment reduced HMGB1 and TLR4 protein levels. In conclusion, PIN pretreatment effectively protected hepatocytes from HIRI and inhibited the HMGB1/TLR4 signaling pathway.
肝缺血再灌注损伤(HIRI)在肝外科手术和肝移植中很常见。白杨素(PIN)是从当地传统中药桃儿七(P. chinense)中提取的一种类黄酮单体。然而,PIN 对 HIRI 的影响尚未确定。我们研究了 PIN 对 HIRI 的保护作用及其潜在机制。模型小鼠进行 60 分钟部分肝缺血,实验小鼠用 PIN 口服预处理 7 天,体外建立 AML12 肝细胞 H2O2 诱导的氧化损伤模型。组织病理分析和血清生化水平表明,PIN 对 HIRI 具有肝保护作用。GSH、SOD、MDA 和 ROS 水平的变化表明,PIN 处理减轻了组织中的氧化应激。PIN 预处理明显改善了细胞凋亡,并抑制了体内 HMGB1 和 TLR4 的表达。在体外,与 H2O2 组相比,ROS、线粒体膜电位、凋亡细胞和 Bcl-2 蛋白的含量降低,而 Bax 蛋白表达增加。此外,HMGB-1 小干扰 RNA 试验和 Western blot 表明,PIN 预处理降低了 HMGB1 和 TLR4 蛋白水平。综上所述,PIN 预处理可有效保护肝细胞免受 HIRI,并抑制 HMGB1/TLR4 信号通路。