Kusniec F, Fischer G, Sela B A, Ashkenazy Y, Feigel D, Moshonov S, Zor U
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
J Basic Clin Physiol Pharmacol. 1994 Jan-Mar;5(1):45-58.
The pathophysiological responses to immune stress (IS) include activation of several processes which are dependent on cytosolic Ca2+ elevation. Magnesium frequently acts as a natural Ca2+ antagonist. In this study we have observed that Mg2+ can protect guinea-pigs against IS. Antigen-sensitized guinea-pigs, which had been fed a magnesium-deficient diet, were given a single dose (15 mg) of MgCl2 intraperitoneally 1 h before antigen challenge. The development of anaphylactic shock (AS) was observed during the next 2 h, and the hearts were subsequently examined histologically for signs of cardiac myolysis (CM). Magnesium (i) reduced the incidence of CM from 40% to 10% (p < 0.05); (ii) reduced the incidence of AS from 61% to 35% (p < 0.05); (iii) attenuated the severity of the AS; and (iv) lowered mortality from 39% in the control to 19% in the Mg(2+)-treated group (p = 0.1). Serum and tissue total [Mg2+] were not affected by the administration of MgCl2. Also, the serum and heart Mg2+ levels were the same whether or not the guinea-pigs developed AS or CM. In cell culture we demonstrated that by elevating the [Mg2+] in the medium bathing sensitized rat basophilic leukemia (RBL) cells, the increase in cytosolic [Ca2+] subsequent to antigen challenge was reduced from 174 +/- 23.28% (1 mM) to 82.74 +/- 13.22% (3 mM). We conclude that a single treatment with Mg2+ can considerably diminish damage induced by immune stress, probably by its altering the Ca2+: Mg2+ ratio. Since the physiological reaction to different types of stress is similar, Mg2+ could prove beneficial in preventing stress-induced shock in general. Studies examining the mechanisms by which Mg2+ exerts its effects thus provide a scientific basis for the current clinical use of Mg2+ in acute myocardial infarction (AMI) and asthma.
对免疫应激(IS)的病理生理反应包括激活几个依赖于胞质Ca2+升高的过程。镁经常作为一种天然的Ca2+拮抗剂。在本研究中,我们观察到Mg2+可以保护豚鼠免受免疫应激。将喂食缺镁饮食的抗原致敏豚鼠在抗原攻击前1小时腹腔注射单剂量(15毫克)MgCl2。在接下来的2小时内观察过敏性休克(AS)的发展情况,随后对心脏进行组织学检查以寻找心肌溶解(CM)的迹象。镁(i)将CM的发生率从40%降低到10%(p<0.05);(ii)将AS的发生率从61%降低到35%(p<0.05);(iii)减轻了AS的严重程度;(iv)将死亡率从对照组的39%降低到Mg(2+)治疗组的19%(p = 0.1)。血清和组织总[Mg2+]不受MgCl2给药的影响。此外,无论豚鼠是否发生AS或CM,血清和心脏Mg2+水平都是相同的。在细胞培养中,我们证明,通过提高致敏大鼠嗜碱性白血病(RBL)细胞培养基中的[Mg2+],抗原攻击后胞质[Ca2+]的增加从174±23.28%(1 mM)降低到82.74±13.22%(3 mM)。我们得出结论,单次使用Mg2+治疗可以显著减少免疫应激诱导的损伤,可能是通过改变Ca2+:Mg2+比值。由于对不同类型应激的生理反应相似,Mg2+可能总体上对预防应激诱导的休克有益。研究Mg2+发挥作用的机制为目前Mg2+在急性心肌梗死(AMI)和哮喘中的临床应用提供了科学依据。