Penkowa M, Giralt M, Thomsen P S, Carrasco J, Hidalgo J
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark.
J Neurotrauma. 2001 Apr;18(4):447-63. doi: 10.1089/089771501750171056.
The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured brains, zinc deficiency only affected significantly lectin (increasing) and glial fibrillary acidic protein (GFAP) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (decreasing) immunoreactivities (irs). In injured brains, a profound gliosis was observed in the area surrounding the lesion, along with severe damage to neurons as indicated by neuron specific enolase (NSE) ir, and the number of cells undergoing apoptosis (measured by TUNEL) was dramatically increased. Zinc deficiency significantly altered brain response to TBI, potentiating the microgliosis and reducing the astrogliosis, while increasing the number of apoptotic cells. Metallothioneins (MTs) are important zinc- and copper-binding proteins in the CNS, which could influence significantly the brain response to TBI because of their putative roles in metal homeostasis and antioxidant defenses. MT-I+II expression was dramatically increased by TBI, and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All these effects were attributable to zinc deficiency, since pair-fed rats did not differ from normally fed rats. In general, copper deficiency caused a similar pattern of responses, albeit more moderate. Results obtained in mice with a null mutation for the MT-I+II isoforms strongly suggest that most of the effects observed in the rat brain after zinc and copper deficiencies are attributable to the concomitant changes in the MT expression.
已在成年大鼠中评估了缺锌和缺铜饮食对创伤性脑损伤（TBI）炎症反应的作用。正如预期的那样，缺锌会降低食物摄入量和体重增加，且后一种影响比在配对喂养大鼠中观察到的更为明显。在未受伤的大脑中，缺锌仅显著影响凝集素（增加）、胶质纤维酸性蛋白（GFAP）和铜锌超氧化物歧化酶（Cu,Zn-SOD）（减少）的免疫反应性（irs）。在受伤的大脑中，在损伤周围区域观察到严重的胶质增生，同时神经元特异性烯醇化酶（NSE）免疫反应性表明神经元受到严重损伤，并且通过TUNEL检测的凋亡细胞数量显著增加。缺锌显著改变了大脑对TBI的反应，增强了小胶质细胞增生并减少了星形胶质细胞增生，同时增加了凋亡细胞的数量。金属硫蛋白（MTs）是中枢神经系统中重要的锌和铜结合蛋白，由于它们在金属稳态和抗氧化防御中的假定作用，可能会显著影响大脑对TBI的反应。TBI使MT-I+II表达显著增加，而这种反应因缺锌而明显减弱。MT-III同工型在TBI和缺锌时均适度增加。TBI强烈增加氧化应激水平，丙二醛（MDA）、蛋白质酪氨酸硝化（NITT）和核因子κB（NF-κB）水平免疫反应性均证明了这一点，所有这些在缺锌时均增强。进一步分析揭示了除MT外促氧化剂和抗氧化剂蛋白的表达失衡，因为缺锌分别增加和降低了诱导型一氧化氮合酶（iNOS）和Cu,Zn-SOD的水平。所有这些影响都归因于缺锌，因为配对喂养的大鼠与正常喂养的大鼠没有差异。总体而言，缺铜引起了类似的反应模式，尽管程度较轻。在MT-I+II同工型基因敲除小鼠中获得的结果强烈表明，大鼠大脑中缺锌和缺铜后观察到的大多数影响归因于MT表达的伴随变化。
