Fang Peng, Dou Bo, Liang Jiajun, Hou Weixin, Ma Chongyang, Zhang Qiuyun
Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
Evid Based Complement Alternat Med. 2021 Oct 25;2021:2898995. doi: 10.1155/2021/2898995. eCollection 2021.
Acute on chronic liver failure (ACLF) is a syndrome of acute liver failure that occurs on the basis of chronic liver disease, which is characterized by a rapid deterioration in a short period and high mortality. High mobility group box 1 (HMGB1) may be involved in the pathological process of ACLF; its specific role remains to be further elucidated. Our previous studies have shown that quercetin (Que) exerts anti-oxidant and anti-apoptotic effects by inhibiting HMGB1 in vitro. The present study aimed to investigate the effect of Que on liver injury in ACLF rats.
The contents of ALT, AST, TBiL, and PT time of rats in each group were observed. HE staining was used to detect liver pathology. The levels of oxidative stress indicators such as MDA, GSH, and 4-HNE in the rat liver were detected. TUNEL assay was used to detect apoptosis in rat hepatocytes. Immunofluorescence and western blot analysis were performed to explore the protective effect of Que on ACLF rats and the underlying mechanism.
The results showed that Que could reduce the increase of serum biochemical indices, improve liver pathology, and reduce liver damage in ACLF rats. Further results confirmed that Que reduced the occurrence of oxidative stress and apoptosis of hepatocytes, and these reactions may aggravate the progress of ACLF. Meanwhile, the results of immunofluorescence and western blotting also confirmed that the expression of HMGB1 and extranuclear translocation in ACLF rat hepatocytes were significantly increased, which was alleviated by the treatment of Que. In addition, when cotreated with glycyrrhizin (Gly), an inhibitor of HMGB1, the inhibition of Que on HMGB1 and its translocation, apoptosis and oxidative stress, and the related proteins of HMGB1-mediated cellular pathway have been significantly enhanced.
Thus, Que alleviates liver injury in ACLF rats, and its mechanism may be related to oxidative stress and apoptosis caused by HMGB1 and its translocation.
慢加急性肝衰竭（ACLF）是在慢性肝病基础上发生的急性肝衰竭综合征，其特点是在短时间内迅速恶化且死亡率高。高迁移率族蛋白B1（HMGB1）可能参与ACLF的病理过程；其具体作用仍有待进一步阐明。我们之前的研究表明，槲皮素（Que）在体外通过抑制HMGB1发挥抗氧化和抗凋亡作用。本研究旨在探讨Que对ACLF大鼠肝损伤的影响。
观察各组大鼠的谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBiL）含量及凝血酶原时间（PT）。采用苏木精-伊红（HE）染色检测肝脏病理。检测大鼠肝脏中丙二醛（MDA）、谷胱甘肽（GSH）和4-羟基壬烯醛（4-HNE）等氧化应激指标水平。采用末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）检测大鼠肝细胞凋亡。进行免疫荧光和蛋白质印迹分析以探讨Que对ACLF大鼠的保护作用及其潜在机制。
结果表明，Que可降低ACLF大鼠血清生化指标的升高，改善肝脏病理，减轻肝损伤。进一步结果证实，Que减少了肝细胞氧化应激和凋亡的发生，而这些反应可能会加重ACLF的进展。同时，免疫荧光和蛋白质印迹结果也证实，ACLF大鼠肝细胞中HMGB1的表达及核外转位显著增加，而Que治疗可使其减轻。此外，当与HMGB1抑制剂甘草酸（Gly）联合处理时，Que对HMGB1及其转位、凋亡和氧化应激以及HMGB1介导的细胞通路相关蛋白的抑制作用显著增强。
因此，Que减轻ACLF大鼠的肝损伤，其机制可能与HMGB1及其转位引起的氧化应激和凋亡有关。
