Polaprezinc Protects Mice against Endotoxin Shock
Polaprezinc Protects Mice against Endotoxin Shock
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DOI：
10.3164/jcbn.09-125
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发表时间：
2010-05-01
影响因子：
2.4
通讯作者：
Matsura, Tatsuya
中科院分区：
文献类型：
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作者：
Ohata, Shuzo;Moriyama, Chihiro;Matsura, Tatsuya
Polaprezinc（PZ）是一种由锌和L-肌肽（Car）组成的螯合物，是日本开发的抗溃疡药物。在本研究中，我们调查是否PZ抑制死亡率，肺部炎症，血浆一氧化氮（NO）和肿瘤坏死因子（TNF）-α水平的内毒素休克小鼠腹腔注射脂多糖（LPS）后，以及如何PZ保护LPS诱导的内毒素休克。PZ预处理可抑制LPS注射后小鼠存活率的下降。PZ抑制LPS后血浆NO和TNF-α的升高。显然，PZ抑制LPS诱导的小鼠肺中诱导型NO合酶mRNA的转录。PZ还改善LPS诱导的肺损伤。然而，PZ并不增强LPS后小鼠肺中热休克蛋白（HSP）70的诱导。用PZ预处理RAW 264细胞抑制LPS加入后NO和TNF-α的产生。这种抑制可能是由于PZ对LPS介导的核因子-κ B（NF-κ B）活化的抑制作用。硫酸锌，但不是汽车，抑制LPS后NO的产生。这些结果表明，PZ，特别是其锌亚组分，通过抑制NF-κ B活化和随后诱导促炎产物如NO和TNF-α而不是HSP诱导来抑制LPS诱导的内毒素休克。
Polaprezinc (PZ), a chelate compound consisting of zinc and L-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-alpha levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-alpha after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-alpha after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-kappa B (NF-kappa B) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc sub-component, inhibits LPS-induced endotoxin shock via the inhibition of NF-kappa B activation and subsequent induction of proinflammatory products such as NO and TNF-alpha, but not HSP induction.