Department of Pathophysiology, Chongqing Medical University, 1 Yixueyuan Road, Chongqing, 400016, China.
Department of Obstetrics and Gynaecology and Pediatrics, Chongqing Medical and Pharmaceutical College, 82 Daxuecheng Road, Chongqing, 401331, China.
J Biochem Mol Toxicol. 2019 Sep;33(9):e22372. doi: 10.1002/jbt.22372. Epub 2019 Jul 23.
β-Hydroxybutyrate (BHB), one of ketone body, has been traditionally regarded as an alternative carrier of energy, but recent studies found that BHB plays versatile roles in inflammation. It has been previously reported that the level BHB declined in mice with lipopolysaccharide (LPS)/d-galactosamine (d-Gal)-induced liver damage, but the pathological significance remains unclear. In the present study, the pathophysiological roles of BHB in LPS/d-Gal-induced hepatic damage has been investigated. The results indicated pretreatment with BHB further enhanced LPS/d-Gal-induced elevation of aspartate aminotransferase and alanine aminotransferase, exacerbated the histological abnormalities and increased the mortality. Pretreatment with BHB upregulated the level of tumor necrosis factor α and interleukin-6 in plasma, promoted the activities of caspase-3, caspase-8, and caspase-9 and increased the count of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. In addition, post-insult supplement with BHB also potentiated LPS/d-Gal-induced apoptotic liver damage. Therefore, BHB might be a detrimental factor in LPS/d-Gal-induced liver injury via enhancing the inflammation and the apoptosis in the liver.
β-羟丁酸（BHB）是酮体的一种，传统上被认为是能量的替代载体，但最近的研究发现 BHB 在炎症中发挥着多种作用。先前有报道称，脂多糖（LPS）/D-半乳糖胺（D-Gal）诱导的肝损伤小鼠中 BHB 水平下降，但病理意义尚不清楚。在本研究中，研究了 BHB 在 LPS/D-Gal 诱导的肝损伤中的病理生理作用。结果表明，BHB 预处理进一步增强了 LPS/D-Gal 诱导的天门冬氨酸氨基转移酶和丙氨酸氨基转移酶升高，加重了组织学异常，并增加了死亡率。BHB 预处理上调了血浆中肿瘤坏死因子-α和白细胞介素-6 的水平，促进了半胱天冬酶-3、半胱天冬酶-8 和半胱天冬酶-9 的活性，并增加了末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性细胞的计数。此外，LPS/D-Gal 诱导后补充 BHB 也增强了凋亡性肝损伤。因此，BHB 可能通过增强肝脏的炎症和凋亡，成为 LPS/D-Gal 诱导肝损伤的有害因素。
