Zhang Hong, Liu Yang, Wang Li-Kun, Wei Na
Internal Medicine Department No. 2, Linyi Chest Hospital in Shandong Province, Linyi City, Shandong Province 276034, China.
Child Healthcare Department, Linyi Chest Hospital in Shandong Province, Linyi City, Shandong Province 276034, China.
Asian Pac J Trop Med. 2017 May;10(5):520-523. doi: 10.1016/j.apjtm.2017.05.010. Epub 2017 May 19.
To study the effect of pyrrolidine dithiocarbamate (PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism.
Clean male SD rats were selected as experimental animals and randomly divided into normal group, model group, PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC, and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention, the rats were executed, and the liver injury indexes, inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression, liver injury indexes, inflammation indexes and oxidative stress indexes in liver tissue were determined.
p-JAK2, p-STAT3, TNF-α, IL-1β, IL-6, ROS, 8-OHdG and MDA expression in liver tissue as well as TBIL, ALT, AST, γ-GT, TNF-α, IL-1β, IL-6, 8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2, p-STAT3, TNF-α, IL-1β, IL-6, ROS, 8-OHdG and MDA expression in liver tissue as well as TBIL, ALT, AST, γ-GT, TNF-α, IL-1β, IL-6, 8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group.
PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.
研究吡咯烷二硫代氨基甲酸盐（PDTC）对抗结核药物性肝损伤的影响及其分子机制。
选取清洁级雄性SD大鼠作为实验动物，随机分为正常组、模型组、PDTC组和AG490组。采用异烟肼+利福平灌胃建立抗结核药物性肝损伤动物模型。PDTC组腹腔注射PDTC，AG490组腹腔注射AG490。干预28天后处死大鼠，检测血清中肝损伤指标、炎症指标和氧化应激指标以及肝组织中JAK2/STAT3表达、肝损伤指标、炎症指标和氧化应激指标。
模型组肝组织中p-JAK2、p-STAT3、TNF-α、IL-1β、IL-6、ROS、8-OHdG和MDA表达以及血清中TBIL、ALT、AST、γ-GT、TNF-α、IL-1β、IL-6、8-OHdG和MDA水平均显著高于正常组；而PDTC组和AG490组肝组织中p-JAK2、p-STAT3、TNF-α、IL-1β、IL-6、ROS、8-OHdG和MDA表达以及血清中TBIL、ALT、AST、γ-GT、TNF-α、IL-1β、IL-6、8-OHdG和MDA水平均显著低于模型组。
PDTC可抑制JAK2/STAT3信号通路介导的炎症和氧化应激，减轻抗结核药物性肝损伤。
