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Abstract：
Hepatic oxidative stress is an important mechanism of Cd-induced hepatotoxicity, and it is ameliorated by TMP. However, this underlying mechanism remains to be elucidated. To investigate the mechanism of the protective effect of TMP on liver injuries in mice induced by subchronic cadmium exposure, 60 healthy male ICR mice were randomly divided into five groups of 12 mice each, namely, control (CON), Cd (2 mg/kg of CdCl2), Cd + 100 mg/kg of TMP, Cd + 150 mg/kg of TMP, and Cd + 200 mg/kg of TMP, and were acclimatized and fed for 7 d. The five groups of mice were gavaged for 28 consecutive days with a maximum dose of 0.2 mL/10 g/day. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study show that compared with the Cd group, TMP attenuated CdCl2-induced pathological changes in the liver and improved the ultrastructure of liver cells, and TMP significantly decreased the MDA level (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection show that TMP significantly increased the levels of Nrf2 in the liver compared with the Cd group as well as the HO-1 and mRNA expression levels in the liver (p < 0.05). In conclusion, TMP could inhibit oxidative stress and attenuate Cd group-induced liver injuries by activating the Nrf2 pathway.
摘要：
肝脏氧化应激是镉致肝脏毒性的重要机制,TMP改善了它。然而,这种潜在的机制仍有待阐明。探讨TMP对亚慢性镉染毒小鼠肝损伤的保护作用机制。将60只健康雄性ICR小鼠随机分为5组,每组12只,即,控制(CON),Cd（2mg/kg的CdCl2），Cd+100mg/kg的TMP，Cd+150mg/kg的TMP，和Cd+200mg/kg的TMP，并适应并喂养7d。将五组小鼠连续28天进行最大剂量为0.2mL/10g/天的灌胃。除了对照组,所有组均在实验的最后一天通过腹膜内注射氟化物（35mg/kg）。本研究结果表明,与Cd组相比,TMP减轻了CdCl2诱导的肝脏病理变化，改善了肝细胞的超微结构，TMP显著降低MDA水平(p<0.05),升高T-AOC水平,T-SOD,和GSH(p<0.05)。mRNA检测结果显示，与Cd组相比，TMP显著提高了肝脏中Nrf2的水平以及肝脏中HO-1和mRNA的表达水平（p<0.05）。总之,TMP可以通过激活Nrf2途径抑制氧化应激并减轻Cd组诱导的肝损伤。
