Zhang Zhixiang, Guo Jinwei, Zhu Jincan
Department of Infectious Diseases, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, 518106, China.
Open Life Sci. 2024 Jul 24;19(1):20220919. doi: 10.1515/biol-2022-0919. eCollection 2024.
The mortality rate of acute-on-chronic liver failure (ACLF) remains significantly elevated; hence, this study aimed to investigate the impact of heat shock protein family B (small) member 1 (HSPB1) on ACLF and and the underlying mechanism. This study used the ACLF mouse model, and liver damage extent was studied employing Masson trichrome, hematoxylin and eosin (H&E), Sirius red staining, and serum biochemical indices. Similarly, hepatocyte injury in lipopolysaccharide (LPS)-induced L02 cells was evaluated using cell counting kit-8 assay, enzymatic activity, flow cytometry, and TUNEL assay, while the underlying mechanism was investigated using western blot. Results showed that the morphology of liver tissue in ACLF mice was changed and was characterized by cirrhosis, fibrosis, collagen fiber deposition, inflammatory cell infiltration, and elevated liver injury indices. Moreover, HSPB1 was upregulated in both ACLF patients and mice, where overexpressing HSPB1 was found to inhibit ACLF-induced liver damage. Similarly, the HSPB1 expression in LPS-treated L02 cell lines was also increased, where overexpressing HSPB1 was found to promote cell viability, inhibit liver injury-related enzyme activity, and suppress apoptosis. Mechanistic investigations revealed that HSPB1 was responsible for inhibiting p-P53 and Bax protein levels, where activated P53 counteracted HSPB1's effects on cellular behaviors. In conclusion, HSPB1 attenuated ACLF-induced liver injury and inhibited LPS-induced hepatocyte damage , suggesting that HSPB1 may be a novel target for ACLF therapy.
急性-on-慢性肝衰竭（ACLF）的死亡率仍然显著升高；因此，本研究旨在探讨热休克蛋白家族B（小）成员1（HSPB1）对ACLF的影响及其潜在机制。本研究使用了ACLF小鼠模型，并采用Masson三色染色、苏木精和伊红（H&E）染色、天狼星红染色以及血清生化指标来研究肝损伤程度。同样，使用细胞计数试剂盒-8检测、酶活性检测、流式细胞术和TUNEL检测来评估脂多糖（LPS）诱导的L02细胞中的肝细胞损伤，同时使用蛋白质免疫印迹法来研究潜在机制。结果显示，ACLF小鼠肝脏组织的形态发生了改变，其特征为肝硬化、纤维化、胶原纤维沉积、炎性细胞浸润以及肝损伤指标升高。此外，HSPB1在ACLF患者和小鼠中均上调，其中发现过表达HSPB1可抑制ACLF诱导的肝损伤。同样，LPS处理的L02细胞系中HSPB1的表达也增加，其中发现过表达HSPB1可促进细胞活力、抑制肝损伤相关酶活性并抑制细胞凋亡。机制研究表明，HSPB1负责抑制p-P53和Bax蛋白水平，其中活化的P53抵消了HSPB1对细胞行为的影响。总之，HSPB1减轻了ACLF诱导的肝损伤并抑制了LPS诱导的肝细胞损伤，表明HSPB1可能是ACLF治疗的一个新靶点。
