Regulation of septic shock by carcitonin-gene related peptide

内毒素可降低大鼠全身血压，升高肺组织iNOS和肿瘤坏死因子-α水平。脂多糖还可增加辣椒素敏感感觉神经元CGRP的释放，从而提高血浆水平。为了确定内源性降钙素基因相关肽是否参与感染性休克的发病机制，我们观察了化学去神经因子辣椒素对内毒素休克大鼠模型的影响。Capsazepin可降低血浆CGRP水平，升高肺组织中TNF-α水平和iNOS活性。Capsazepin可加重内毒素休克。降钙素基因相关肽拮抗剂CGRP8-37也可增加肿瘤坏死因子-α和诱导型一氧化氮合酶活性，从而加重内毒素休克。相反，外源性CGRP可改善内毒素诱导的感染性休克。这些结果表明，辣椒素敏感感觉神经元释放的CGRP可预防休克的发生。降钙素基因相关肽对休克的保护作用可被环氧合酶抑制剂吲哚美辛所抵消，提示降钙素基因相关肽的这种保护作用是通过产生前列环素来实现的。

Systemic blood pressure was decreased and lasma levels of TNF-alpha and lung iNOS level were increased by LPS administration in rats. LPS administration also increased CGRP release from capsaicin sensitive sensory neurons thereby increased plasma levels. To determine whether the intrinsic CGRP contributes to pathogenesis of septic shock, we examined effect of capsazepin, chemical denervation factor, on rat LPS-induced shock model. Plasma CGRP levels were decreased and TNF-alpha levels and iNOS activity in lung were increased by capsazepin pretreatment. LPS-induced shock was worsen by capsazepin. CGRP8-37, an antagonist of CGRP, also increased TNF-alpha and iNOS activity thereby worsen LPS-induced shock. In contrast, exogenous administration of CGRP improved septic shock induced by LPS administration. These results indicated that CGRP released from capsaicin sensitive sensory neurons prevents pathogenesis of shock. This effect of CGRP to prevent shock was cancelled by indomethacin, an inhibitor of cyclooxgenase, suggesting that this protective effect of CGRP is mediated by prostacyclin production.