灵芝酸A对D-氨基半乳糖/脂多糖诱导小鼠肝损伤的保护作用

目的?研究灵芝酸A对D-氨基半乳糖(D-GaIN)/脂多糖(LPS)诱导小鼠肝损伤的保护作用及其相关机制。方法?60只C57BL/6小鼠随机分为4组:正常组、模型组、灵芝酸A低剂量组（20?mg/kg）、灵芝酸A高剂量组（40?mg/kg）。除正常组和模型组给予等体积蒸馏水外，其余各组每天灌胃给予相应剂量药物，共7?d。末次给药4?h后，腹腔注射D-GalN(700?mg/kg)与LPS(1?mg/kg)，正常组腹腔注射等体积溶媒。24?h后取血、肝脏。ELISA法检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）活性以及白介素（IL-6、IL-1β）和肿瘤坏死因子-α（TNF-α）含量，各组小鼠肝脏做HE染色，并采用蛋白免疫印迹法（Western blot）检测肝脏组织中NLRP3/NF-κB蛋白表达。结果?灵芝酸A（20、40?mg/kg）能显著降低D-GaIN/LPS诱导的肝损伤小鼠血清ALT、AST活性及IL-6、IL-1β和TNF-α含量；能显著改善小鼠肝组织的病理学改变；显著降低肝脏NLRP3/NF-κB蛋白表达。结论?灵芝酸A对D-GaIN/LPS诱导的小鼠肝损伤具有保护作用，这种效应可能与调控NLRP3/NF-κB信号通路有关。 

Protective Effect of Ganoderic Acid A on Hepatic Injury Induced by D-GalN/LPS in Mice

OBJECTIVE?To observe the effect of ganoderic acid A (GA) on D-GalN/LPS induced liver injury in mice. METHODS?60 male C57BL/6 mice were randomly divided into 4 groups: normal control group， D-GalN/LPS group， D-GalN/LPS+ GA (20?mg/kg) group， D-GalN/LPS+GA (40?mg/kg) group. Mice in the normal control group and D-GalN/LPS group were given distilled water while other groups were given drugs for 7?d by gavage. After the last dose of 4?h， D-GalN (700?mg/kg) and LPS (1?mg/kg) were given by intraperitoneal injection， and the mice in normal control group were given same volume of vegetable oil solution. 24?h after established model， the blood and liver were collected. Aspartate aminotransaminase（AST），alanine aminotransaminase（ALT），interleukin-6 (IL-6)， interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) were measured by corresponding kits. Hematoxylin (HE) staining was used to observe the changes of hepatic histopathology.Western blotting was used to demonstrate the expression levels of related protein. RESULTS?GA significantly reduced levels of AST，ALT，IL-6， IL-1β and TNF-α in serum. In addition， GA regulated proteins levels of NLRP3/NF-κB pathway in liver. CONCLUSION?GA shows the therapeutical effect on D-GalN/LPS induced liver injury in mice which may be related to the regulation of NLRP3/NF-κB pathway.