纳米红色元素硒与葡萄糖醛酸内酯联用对大鼠肝纤维化形成过程的干预及其定量分析

Quantitative analyses of the combined effects of nano red elemental selenium and glucurolactone on forming liver fibrosis induced by CCl_4 in rats

目的 将纳米红色元素硒 (nanoredelementalseleni um ,Nse)与葡萄糖醛酸内酯 μglucurolactone ,Glu)联用 ,观察对大鼠肝纤维化形成过程的干预作用 ,试图通过药物间的相互作用 ,增效减毒 ,从而降低硒用量。方法 根据权重配方法设计 ,设立两药不同组合的 6个用药组和 2个对照组。用CCl4 造成大鼠急性肝损伤后开始用药 ,于用药 3wk和 6wk ,观察与急慢性肝损伤的相关指标 ,包括ALT ,MDA和PCIII。结果 急性肝损伤阶段的短期用药 (3wk) ,宜用大剂量Nse ,权重配方法的理论计算提示 ,Nse 2 0 0 μg·kg-1单用即可 ;两药联合长期使用 (6wk) ,在小剂量就可获效 ,尤以Nse 10 0 μg·kg-1+Glu 5 0mg·kg-1为好 ,对大鼠实验性肝纤维化已呈现明显的防治作用 ,联用Nse和Glu作用强于单用Nse。理论计算认为 ,Nse和Glu间产生协同作用 ,优化的组合剂量为Nse 10 0 μg·kg-1+Glu 6 0mg·kg-1(ig)。 结论 Nse和Glu联合用药 ,对大鼠CCl4 所致的肝纤维化有防治作用 ,可降低Nse用量。

AIM To observe the combined effects of nano red elemental selenium (Nse) and glucurolactone (Glu) on forming liver fibrosis in rats, and to search for a low dose of Nse with therapeutic effect. METHODS According to the weighted modification method, six compound-dose groups and 2 control groups were set. The rats were given (sc) CCl 4 for 10 wk, and the administration began at 4 wk. The indices related to acute liver damage were determined 3 wk after the administration, and to chronic liver damage 6 wk after the administration. RESULTS At the stage of acute liver damage and within the therapeutic duration of 3 wk, Nse should be used at a larger dose in combination with Glu. Theoretical analysis showed that Nse 200 μg·kg -1 alone was available by the weighted modification method. However, in the combination of Nse and Glu for the chronic liver injury, Nse should be given at a low dose. There was a synergism between Nse and Glu, and some compound-dose groups showed the preventive and therapeutic effect, especially in a dose of Nse 100 μg·kg -1 + Glu 60 mg·kg -1 . But theoretical analysis exhibited that Nse 100 μg·kg -1 + Glu 60 mg·kg -1 (ig) might be an optimal combination. CONCLUSION The combination of Nse and Glu has significant effect in prevention and treatment of the live fibrosis in rats, and it can decrease dose of Nse used.