Department of Pathophysiology, Chongqing Medical University, China.
Clinical Medical School, Chongqing Medical and Pharmaceutical College, China.
Innate Immun. 2021 Feb;27(2):201-209. doi: 10.1177/1753425920988330.
Increasing evidence indicates that signal transducer and activator of transcription 3 (STAT3), a vital transcription factor, plays crucial roles in the regulation of inflammation. STAT3 has become a novel therapeutic target for intervention in inflammation-related disorders. However, it remains unclear whether STAT3 plays a part in acute hepatic damage. To investigate the effects of STAT3 here, LPS/d-GalN-induced hepatic damage was induced in mice, the STAT3 inhibitor Stattic was administered, and the degree of liver injury, inflammation, and hepatocyte apoptosis were investigated. The results showed that Stattic mitigated the hepatic morphologic abnormalities and decreased the level of aminotransferase in LPS/D-GalN-insulted mice. The results also indicated that Stattic decreased the levels of TNF-α and IL-6, prevented the activation of the caspase cascade, suppressed cleavage of PARP, and decreased the quantity of TUNEL-positive cells. These results suggest that Stattic provided protective benefits in LPS/d-GalN-induced hepatic damage, and the protective effects might be associated with its anti-inflammatory and anti-apoptotic effects. Therefore, STAT3 might become a novel target for intervening in inflammation-based and apoptosis-based hepatic disorders.
越来越多的证据表明,信号转导子和转录激活子 3(STAT3)作为一种重要的转录因子,在炎症调节中发挥着关键作用。STAT3 已成为干预炎症相关疾病的新的治疗靶点。然而,STAT3 是否在急性肝损伤中发挥作用仍不清楚。为了研究 STAT3 的作用,本研究在小鼠中诱导 LPS/d-GalN 诱导的肝损伤,给予 STAT3 抑制剂 Stattic,并观察肝损伤、炎症和肝细胞凋亡的程度。结果表明,Stattic 减轻了 LPS/D-GalN 损伤小鼠的肝形态异常,并降低了转氨酶水平。结果还表明,Stattic 降低了 TNF-α 和 IL-6 的水平,防止了半胱天冬酶级联的激活,抑制了 PARP 的裂解,并减少了 TUNEL 阳性细胞的数量。这些结果表明,Stattic 在 LPS/d-GalN 诱导的肝损伤中提供了保护作用,其保护作用可能与其抗炎和抗凋亡作用有关。因此,STAT3 可能成为干预基于炎症和基于凋亡的肝疾病的新靶点。