吡咯烷二硫代氨基甲酸盐对抗结核药所致肝损伤时高迁移率族蛋白B1表达的影响

发布时间：2018-06-23 12:38

本文选题：核因子-κB + 高迁移率族蛋白B　；参考：《中国临床药理学杂志》2015年07期

【摘要】：目的研究异烟肼、利福平合用致肝损伤时高迁移率族蛋白B1(HMGB1)与核因子-κB的关系及吡咯烷二硫代氨基甲酸盐(PDTC)对肝损伤的作用。方法 48只雄性SD大鼠随机分为3组:正常组、模型组(异烟肼+利福平,均50mg·kg-1·d-1)、PDTC组(异烟肼+利福平+PDTC,均50 mg·kg-1·d-1)。造模第14,28天,分批处死大鼠,检测大鼠血清胆汁酸(TBA)、总胆红素(TBIL)、直接胆红素(DBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)水平,观察大鼠肝病理学变化,免疫组化法检测肝HMGB1蛋白表达,凝胶迁移实验测定核因子-κB活性。结果与正常组相比,模型组大鼠血清TBA、TBIL、DBIL、ALP明显升高(P0.01),但ALT、AST差异无统计学意义;肝脂肪变性及炎症细胞浸润明显(P0.01),肝内核因子-κB活性和HMGB1表达水平显著升高。与模型组相比,PDTC组血清TBA、TBIL、DBIL、ALP明显降低(P0.01);肝病理学变化显著改善,肝内核因子-κB活性和HMGB1表达水平显著降低。结论抑制核因子-κB活性可下调HMGB1的表达;PDTC对异烟肼、利福平合用所致肝损伤的保护作用与其抑制NF-κB/HMGB1途径有关。
[Abstract]:Objective to study the relationship between high mobility group protein B1 (HMGB1) and nuclear factor- 魏 B in liver injury induced by isoniazid and rifampicin and the effect of pyrrolidine dithiocarbamate (PDTC) on liver injury. Methods Forty-eight male SD rats were randomly divided into three groups: normal group, model group (isoniazid rifampicin, all 50mg kg-1 d-1) and PDTC group (isoniazid rifampicin, 50 mg kg-1 d -1). The rats were killed in batches on the 28th day of modeling. The levels of serum bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (alt), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were measured. The expression of HMGB1 protein was detected by immunohistochemistry and the activity of nuclear factor- 魏 B was determined by gel migration assay. Results compared with the normal group, the serum levels of TBA TBILB ILP in the model group were significantly higher than those in the normal group (P0.01), but there was no significant difference in ALT AST, the hepatic fatty degeneration and inflammatory cell infiltration (P0.01), the activity of factor 魏 B and the expression of HMGB1 in the liver kernel were significantly increased in the model group. Compared with the model group, the serum TBABILB DBILILP in PDTC group was significantly decreased (P0.01), the hepatic pathological changes were improved significantly, the activity of hepatic nuclear factor- 魏 B and the expression of HMGB1 were significantly decreased in PDTC group. Conclusion inhibiting the activity of nuclear factor- 魏 B can down-regulate the expression of HMGB1. The protective effect of PDTC on hepatic injury induced by isoniazid and rifampicin is related to its inhibition of NF- 魏 B / HMGB1 pathway.
【作者单位】：安徽医科大学第一附属医院消化科·安徽省消化系统疾病重点实验室;安徽医科大学第一附属医院病理科;
【基金】：安徽省自然科学基金资助项目(1208085MH155)
【分类号】：R965

【参考文献】