慢性急性肝衰竭(ACLF)的死亡率仍然显着升高;因此,本研究旨在探讨热休克蛋白家族B(小)成员1(HSPB1)在体内外对ACLF的影响及其机制。本研究采用ACLF小鼠模型,采用马森三色法研究肝损伤程度,苏木精和曙红(H&E),天狼星红染色,和血清生化指标。同样,脂多糖(LPS)诱导的L02细胞的肝细胞损伤使用细胞计数试剂盒-8测定进行评估,酶活性,流式细胞术,和TUNEL分析,而潜在的机制是使用蛋白质印迹研究的。结果表明,ACLF小鼠肝组织形态发生改变,表现为肝硬化,纤维化,胶原纤维沉积,炎性细胞浸润,肝损伤指数升高。此外,HSPB1在ACLF患者和小鼠中均上调,其中发现过表达HSPB1抑制ACLF诱导的肝损伤。同样,LPS处理的L02细胞系中的HSPB1表达也增加,发现过表达HSPB1可以促进细胞活力,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,其中激活的P53抵消了HSPB1对细胞行为的影响。总之,HSPB1在体内减轻ACLF诱导的肝损伤,在体外抑制LPS诱导的肝细胞损伤,提示HSPB1可能是ACLF治疗的新靶点。
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 in vivo and in vitro 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 in vivo and inhibited LPS-induced hepatocyte damage in vitro, suggesting that
HSPB1 may be a novel target for ACLF therapy.