Sobocinski P Z, Canterbury W J
Ann N Y Acad Sci. 1982;389:354-67. doi: 10.1111/j.1749-6632.1982.tb22149.x.
Numerous chemically distinct phlogistic substances have been shown to induce hepatic metallothionein-Zn (MT) accumulation when administered to rats. These findings suggest that induction of this cysteine-rich metalloprotein occurs through the action of some common mediator(s). Possible mediators include substances such as leukocytic endogenous mediator (LEM) and/or hormones known to influence hepatic protein synthesis. Studies were performed to examine further the mechanism(s) and potential mediators involved in endotoxin-induced MT accumulation. Additionally, the studies were performed to determine the possible involvement of genetic factors, which reportedly influence LEM production, in the induced MT response. Endotoxin (ET) was administered ip to rats and to EP-resistant, C3H/HeJ, and susceptible, C3Heb/FeJ, stains of mice. ET induced hypozincemia, hyperglucagonemia, and increased MT concentrations in rats. ET induced hypozincemia and MT accumulation to the same extent in both strains of mice. The induction of tolerance in rats to Zn depressing activity of ET also prevented hyperglucagonemia and additional accumulation of MT. Results suggest that glucagon, but not LEM, may be a common mediator in MT response during inflammatory stress.
当给大鼠施用多种化学性质不同的致炎物质时，已表明它们会诱导肝脏金属硫蛋白 - 锌（MT）积累。这些发现表明，这种富含半胱氨酸的金属蛋白的诱导是通过某些共同介质的作用发生的。可能的介质包括诸如白细胞内源性介质（LEM）和/或已知会影响肝脏蛋白质合成的激素等物质。进行了研究以进一步检查内毒素诱导的MT积累所涉及的机制和潜在介质。此外，进行这些研究是为了确定据报道会影响LEM产生的遗传因素在诱导的MT反应中可能的参与情况。将内毒素（ET）腹腔注射给大鼠以及对EP有抗性的C3H/HeJ小鼠品系和易感的C3Heb/FeJ小鼠品系。ET诱导大鼠出现低锌血症、高胰高血糖素血症并增加MT浓度。ET在两种小鼠品系中诱导低锌血症和MT积累的程度相同。大鼠对ET的锌抑制活性产生耐受性的诱导也可防止高胰高血糖素血症和MT的进一步积累。结果表明，胰高血糖素而非LEM可能是炎症应激期间MT反应中的一种共同介质。
