褪黑素缓解由慢性社会应激所引发的大鼠下丘脑自由基和血清甲状腺素的变化

Melatonin attenuates the change of hypothalamic free radicals and serum thyroxine induced by chronic social stress in rats

目的观察慢性社会应激是否会引起大鼠的氧化应激和神经内分泌的改变以及褪黑素的防治作用。方法大鼠分为对照组、应激组和褪黑素干预组(MLT组)。应激组是将大鼠与攻击性强的刺激鼠及雌性大鼠共同培养于拥挤环境中;MLT组在接受同样应激刺激3 d前,每日18∶00时腹部皮下注射MLT 1次;检测下丘脑脂质过氧化物丙二醛(MDA)、还原型谷胱甘肽(GSH)及谷胱甘肽过氧化物酶(GSH-PX);血浆皮质酮、血清甲状腺相关激素(TT3、TT4、FT3、FT4和TSH)含量测试及行为学实验。结果应激组和MLT组大鼠体质量显著低于对照组(P<0.05)。应激组血浆皮质酮含量显著高于对照组(P<0.05),而MLT组较应激组显著回降(P<0.05),但仍高于对照组(P<0.05)。应激组TT3、TT4、FT3、FT4和TSH含量均显著低于对照组(P<0.05),而MLT组TT3、FT3、FT4和TSH含量较应激组显著回升(P<0.05),但TT3和FT3仍低于对照组(P<0.05),FT4和TSH回升接近于正常水平。应激组GSH-PX活性及GSH含量明显低于对照组(P<0.05)、MDA含量明显高于对照组(P<0.05),而MLT组较应激组GPX活性回升、GSH含量增加、MDA含量降低(P<0.05),但GSH含量仍低于对照组(P<0.05)。此外,旷场实验中应激组大鼠在中心区活动次数明显低于对照组,探究行为能力明显降低。结论 MLT可缓解慢性社会应激诱发的氧化应激及神经内分泌的异常变化。

Objective To observe the effect of melatonin （MLT） on oxidative damage and neuroendocrine derived from chronic social stress （CSS）. Methods Rats were classified into 3 groups： control group,CSS group and MLT group. CSS was induced by rats housed with aggressive male rats and female rats in a crowded cage for 8 days. MIX solution was administered 3 days before accepting CSS stimulation. Results SG and MG exhibited dramatic loss of body weight. Increased plasma corticosterone （CORT） and decreased serum TF3 （total triiodothyronine）, TF4 （ total thyroxine）, FT3 （ free triiodothyronine）, FT4 （ free thyroxine） and TSH （ thyroid stimulating hormone） levels were evident in SG. The activity of glutathione peroxidase （GSH-PX） and content of reduced glutathione （GSH） in stress group （SG） decreased significantly, Melatonin group （MG） showed a significant increase in the activity of GSH-PX and decrease in the content of MDA. In addition, in open field test, scores of horizontal activity in central region in SG were significantly fewer than those in CG and MG. Conclusions CSS can induce oxidative stress and impact on neuroendocrine, e.g. thyroid functions. But these changes were partly reversed or attenuated by MLT.