锌缺乏对小鼠脑发育及功能影响的实验研究

Effect of zinc deficiency on development and function of mice brain

目的：观察发育期（孕期和哺乳期）锌缺乏小鼠子代（成年）学习能力、海马长时程增强（ＬＴＰ）、脑组织金属硫蛋白（ＭＴ）及其ｍ ＲＮＡ的表达情况，初步探讨发育期锌缺乏影响脑功能及发育的机制。方法：将８０ 只刚怀孕ＩＣＲ雌鼠随机分为５组：严重缺锌、轻度缺锌、适锌、高锌对喂及高锌组，饲料含锌量分别为１，５，３０，１００ 及１００ ｍ ｇ／ｋｇ。各组小鼠在孕期和哺乳期均饲喂实验饲料，仔鼠断奶（出生第２０ 天）后改饲喂普通饲料。７０ ｄ 龄后，采用条件性回避反应模型测试仔鼠学习能力，然后在其海马脑片上进行诱导ＬＴＰ的实验；采用Ｗｅｓｔｅｒｎ ｂｌｏｔ和Ｎｏｒｔｈｅｒｎ ｂｌｏｔ技术检测其脑组织中ＭＴ蛋白及ＭＴ－Ⅰｍ ＲＮＡ 表达情况。结果：轻度缺锌组仔鼠达到学会标准所需次数明显多于高锌组（Ｐ＜ ０．００５），而其脑片上诱导的ＬＴＰ却显著低于高锌组（Ｐ＜０．００５）；脑组织中ＭＴ蛋白及ＭＴ－Ⅰｍ ＲＮＡ 表达量的顺序为严重缺锌组＜ 轻度缺锌组＜ 适锌组＜ 高锌对喂组＜ 高锌组。结论：发育期锌缺乏不但可造成学习能力下降、海马突触可塑性受损，同时还可使脑组织中ＭＴ蛋白及其ｍ ＲＮＡ 表达降低；

Objective: To determine the mechanisms of zinc on brain development and function, we observed the learning ability, hippocampal long term potentiation and brain metallothionein (MT) and mRNA expression in mice whose maternal were fed with zinc deficiency diets during pregnancy and lactation. Methods: The learning ability, hippocampal long term potentiation, brain MT and mRNA expression at postnatal day 70 were examined with shuttle box, electric physiology, Western blot and Northern blot respectively, whose dams were fed with zinc deficient diets during pregnancy and lactation. Results: The numbers of trials needed to reach the learning criterion for marginally zinc deficient group (5 mg/kg) offsprings were much more than that of high zinc supplementation group (100 mg/kg) offsprings. Long term potentiation induced from brain slices of marginally zinc deficient group offsprings was smaller than that induced from high zinc supplementation group offsprings. The order of brain MT and mRNA expression level was severe zinc deficiency group (1 mg/kg) < marginal zinc deficiency group < adequate zinc supply group (30 mg/kg) < high zinc pair fed group (100 mg/kg) < high zinc supplementation. Conclusion: Zinc deficiency results not only in injury of learning ability and decrease of hippocampal synaptic plasticity, but also inhibition of MT and mRNA expression. The inhibition of MT transcription may be one of important mechanisms of the impairment to brain development and function.