Vignolini F, Nobili F, Mengheri E
Istituto Nazionale della Nutrizione, Roma, Italy.
Life Sci. 1998;62(2):131-41. doi: 10.1016/s0024-3205(97)01059-x.
In a previous study we have shown that zinc deficiency caused several alterations in intestine of rats. Here we report that interleukin-1beta (IL-1beta) is involved in the zinc deficiency-induced mucosal damage and that cyclosporine A (CsA) protects the intestine against both structural and functional alterations by different mechanisms. The zinc deficient (ZD) rats were maintained on a zinc deficient diet for 40 days. They received a daily injection of CsA (12 mg/kg) for the last 10 days. The histological analysis of small intestine revealed that the dramatic alterations induced by zinc deficiency (ulcerations, inflammation, edema, vasodilatation), were not present after CsA treatment. The IL-1beta gene expression, analyzed by PCR, was increased in the three intestinal regions of ZD rats, as compared to C rats. There was a relation between increasing IL-1beta expression and increased severity of damage, and the highest cytokine elevation was in the most damaged region, i.e. the jejunum. After CsA administration the IL-1beta mRNA was similar to control rats. The intestinal cell proliferation, measured as crypt cell production rate and labelling index, as well the cell renewal, measured as cell migration rate and turnover time, were affected by zinc deficiency. After CsA treatment, all these variables were similar to control rats, suggesting that CsA induces a stimulation of intestinal cell proliferation in zinc deficiency. Finally, the decrease in the disaccharidase activities induced by zinc deficiency was abrogated by CsA treatment.
在之前的一项研究中，我们已表明锌缺乏会导致大鼠肠道出现多种改变。在此我们报告，白细胞介素-1β（IL-1β）参与了锌缺乏诱导的黏膜损伤，并且环孢素A（CsA）通过不同机制保护肠道免受结构和功能改变的影响。锌缺乏（ZD）大鼠维持锌缺乏饮食40天。在最后10天，它们每天接受CsA注射（12 mg/kg）。小肠的组织学分析显示，锌缺乏诱导的显著改变（溃疡、炎症、水肿、血管扩张）在CsA治疗后未出现。通过PCR分析，与C组大鼠相比，ZD大鼠的三个肠道区域中IL-1β基因表达增加。IL-1β表达增加与损伤严重程度增加之间存在关联，并且细胞因子升高最高的是损伤最严重的区域，即空肠。给予CsA后，IL-1β mRNA与对照大鼠相似。以隐窝细胞产生率和标记指数衡量的肠道细胞增殖，以及以细胞迁移率和周转时间衡量的细胞更新，均受到锌缺乏的影响。CsA治疗后，所有这些变量均与对照大鼠相似，表明CsA在锌缺乏状态下诱导肠道细胞增殖。最后，锌缺乏诱导的双糖酶活性降低被CsA治疗所消除。
