目的探讨雷帕霉素对内毒素性肝损伤小鼠肝组织缺氧诱导因子-1(HIF-1)表达的影响。方法健康雄性昆明小鼠36只,随机分为正常组(12)、模型组(12)和雷帕霉素组(12)。应用脂多糖10 mg/kg腹腔注射小鼠诱导内毒素肝损伤模型。造模后6 h取血,检测小鼠血清谷丙转氨酶(ALT)和、谷草转氨酶(AST)活性,免疫组织化学方法和Western blot方法检测各组小鼠肝组织HIF-1的表达。结果模型组血清ALT、AST含量比正常组明显升高(P〈0.01),而雷帕霉素组血清ALT、AST含量比模型组明显降低(P〈0.05)。模型组小鼠肝组织HIF-1表达水平比正常组显著升高(P〈0.01),而雷帕霉素组比模型组显著降低(P〈0.01)。结论雷帕霉素能够下调内毒素性肝损伤小鼠肝组织HIF-1的表达。
Objective To investigate the effect of rapamycin on the expression of hypoxic inducible factor(HIF-1) in liver injury mouse induced by endotoxin. Methods 36 healthy male Kunming mice were randomly divided into normal group(12), model group(12) and rapamycin group(12). Liver injury model was induced by intraperitoneal injection of endotoxin(lipopolysaccharide, LPS, 10 mg /kg). Blood was collected after injection of LPS at 6h, the activity of glutamic pyruvic transaminase(ALT) and aspartate aminotransferase(AST) was detected. The expression of HIF-1 in liver tissue of mice was determined by immunohistochemy and Western blot. Results The contents of ALT and AST in serum were markedly increased in model group than in normal group(P〈0.01), but decreased significantly in rapamycin group than in model group(P〈0.05). The expression level of HIF-1 in liver tissue was increased significantly in model group than in normal group(P〈0.01), however, decreased significantly in rapamycin group than in model group(P〈0.01). Conclusion Rapamycin could downregulate the expression of HIF-1 in liver injury mouse.