L 型钙通道参与介导硫酸镁的抗炎作用。
L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate.
机构信息
Department of Anaesthesiology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China.
出版信息
Br J Anaesth. 2010 Jan;104(1):44-51. doi: 10.1093/bja/aep336.
BACKGROUND
Magnesium sulphate (MgSO(4)) has potent anti-inflammatory capacity. It is a natural calcium antagonist and a potent L-type calcium channel inhibitor. We sought to elucidate the possible role of calcium, the L-type calcium channels, or both in mediating the anti-inflammatory effects of MgSO(4).
METHODS
RAW264.7 cells, an immortalized murine macrophage-like cell line, were treated with phosphate buffered saline, MgSO(4), lipopolysaccharide (LPS), LPS plus MgSO(4), LPS plus MgSO(4) plus extra-cellular supplement with calcium chloride (CaCl(2)), or LPS plus MgSO(4) plus the L-type calcium channel activator BAY-K8644. After harvesting, the production of inflammatory molecules was evaluated. Because the production of endotoxin-induced inflammatory molecules is regulated by the crucial transcription factor nuclear factor (NF)-kappaB, we also evaluated the expression of NF-kappaB.
RESULTS
LPS significantly induced the production of inflammatory molecules, including macrophage inflammatory protein-2, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E(2)/cyclo-oxygenase-2. LPS also induced NF-kappaB activation, as inhibitor-kappaB degradation, NF-kappaB nuclear translocation, and NF-kappaB-DNA binding activity were significantly increased in LPS-treated RAW264.7 cells. MgSO(4), in contrast, significantly inhibited the LPS-induced inflammatory molecules production and NF-kappaB activation. Moreover, the effects of MgSO(4) on inflammatory molecules and NF-kappaB were reversed by extra-cellular calcium supplement with CaCl(2) and L-type calcium channel activator BAY-K8644.
CONCLUSIONS
MgSO(4) significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-kappaB activation in activated RAW264.7 cells. The effects of MgSO(4) on inflammatory molecules and NF-kappaB may involve antagonizing calcium, inhibiting the L-type calcium channels, or both.
背景
硫酸镁（MgSO4）具有强大的抗炎能力。它是一种天然的钙拮抗剂，也是一种有效的 L 型钙通道抑制剂。我们试图阐明钙、L 型钙通道或两者在介导硫酸镁抗炎作用中的可能作用。
方法
RAW264.7 细胞，一种永生化的鼠巨噬样细胞系，用磷酸盐缓冲盐水、硫酸镁、脂多糖（LPS）、LPS 加硫酸镁、LPS 加硫酸镁加氯化钙（CaCl2）外钙补充剂或 LPS 加硫酸镁加 L 型钙通道激活剂 BAY-K8644 处理。收获后，评估炎症分子的产生。由于内毒素诱导的炎症分子的产生受关键转录因子核因子（NF）-κB 的调节，我们还评估了 NF-κB 的表达。
结果
LPS 显著诱导炎症分子的产生，包括巨噬细胞炎症蛋白-2、肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6、一氧化氮/诱导型一氧化氮合酶和前列腺素 E2/环加氧酶-2。LPS 还诱导 NF-κB 激活，因为 LPS 处理的 RAW264.7 细胞中 IκB 降解、NF-κB 核转位和 NF-κB-DNA 结合活性显著增加。相比之下，硫酸镁显著抑制 LPS 诱导的炎症分子产生和 NF-κB 激活。此外，用 CaCl2 和 L 型钙通道激活剂 BAY-K8644 补充细胞外钙以及 L 型钙通道激活剂 BAY-K8644 逆转了硫酸镁对炎症分子和 NF-κB 的作用。
结论
硫酸镁显著抑制激活的 RAW264.7 细胞中内毒素诱导的炎症分子和 NF-κB 的上调。硫酸镁对炎症分子和 NF-κB 的作用可能涉及拮抗钙、抑制 L 型钙通道或两者兼有。
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