柚皮苷改善束缚性应激引起的小鼠生化指标及行为变化的一氧化氮调节机制(英文)

Amelioration of immobilization stress-induced biochemical and behavioral alterations and mitochondrial dysfunction by naringin in mice:possible mechanism of nitric oxide modulation

目的:研究柚皮苷对束缚性应激引起的小鼠生化指标改变、行为变化及线粒体功能紊乱的影响。方法:将小鼠按照体质量随机分组,分别给予不同药物治疗14 d。在第15天让所有小鼠接受束缚性应激刺激6 h,然后在接受各种不同的行为测试后处死。取小鼠的大脑匀浆进行各种生化指标测量和线粒体功能分析。结果:6 h的急性束缚性应激刺激能显著改变小鼠的行为(焦虑和记忆),引起生化指标变化和线粒体功能紊乱。用柚皮苷预处理(50或100 mg/kg口服)14 d则能显著减轻急性束缚性应激刺激引起的小鼠行为和生化指标变化以及线粒体功能紊乱(P<0.05);而使用一氧化氮的前体左旋精氨酸预处理(50 mg/kg腹腔注射)可以拮抗柚皮苷的保护效应(P<0.05)。此外,采用左旋精氨酸甲酯预处理(5 mg/kg腹腔注射)则导致柚皮苷的保护效应增强。结论:柚皮苷对束缚性应激刺激引起的小鼠行为和生化指标变化以及线粒体功能紊乱的保护作用与氮能神经通路有关。

Objective： The present study was undertaken to evaluate the effects of naringin on immobilization stress-induced biochemical-behavioral changes and mitochondrial dysfunction in mice. Methods.. Mice were randomized and grouped based on body weights. Respective drug treatments were given for 14 d, and on the 15th day all the animals were subjected to a 6-hour immobiliza- tion stress; then all the animals were subjected to various behavioral paradigms and were sacrificed. Various biochemical parameters and mitochondrial functions were analyzed using brain homogenate. Results： The 6-hour acute immobilization stress significantly altered the behavioral （anxiety and memory） and biochemical parameters coupled with mitochondrial dysfunction in mice. Fourteen days pretreatment with naringin （50 and 100 mg/kg, per oral） significantly inhibited the behavioral and biochemical alterations and mitochondria stress （P〈0.05）. Further, pretreatment with dysfunction caused by acute immobilization L-arginine （50 mg/kg, intraperitoneally）, a nitric oxide precursor, reversed the protective effect of naringin （P〈0.05）. In addition, pretreatment with N^C -nitro-L-arginine methyl ester （5 mg/kg, intraperitoneally） caused potentiation in the protective effect of naringin. Conclusion： These results suggest the possible involvement of nitrergic pathway in the protective effect of naringin against immobilization stress-induced behavioral, biochemical and mitochondrial dysfunctions in mice.