Regulation of septic shock by carcitonin-gene related peptide

LPS可降低大鼠全身血压，提高血浆tnf - α水平和肺iNOS水平。LPS处理也增加了辣椒素敏感感觉神经元的CGRP释放，从而增加了血浆水平。为了确定内源性CGRP是否参与感染性休克的发病机制，我们检测了辣椒素（化学去神经支配因子）对lps诱导的大鼠休克模型的影响。辣椒素预处理可降低大鼠血浆CGRP水平，提高肺组织tnf - α水平和iNOS活性。辣椒素加重lps致休克。CGRP拮抗剂CGRP8-37也增加了tnf - α和iNOS活性，从而加重了lps诱导的休克。相比之下，外源性给药CGRP可改善LPS引起的感染性休克。这些结果表明辣椒素敏感感觉神经元释放的CGRP可以预防休克的发病机制。CGRP预防休克的这种作用被吲哚美辛（环氧化酶抑制剂）所抵消，这表明CGRP的这种保护作用是由前列环素的产生介导的。

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.