A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis.
A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis.
复制标题
DOI：
10.1136/gut.2008.148551
复制
发表时间：
2008-11
期刊：
影响因子：
24.5
通讯作者：
Liddle RA
中科院分区：
文献类型：
--
作者：
Noble MD;Romac J;Vigna SR;Liddle RA
尽管其潜在机制尚不清楚，但内镜逆行胰胆管造影（ERCP）具有较高的胰腺炎风险。瞬时受体电位香草酸 1 (TRPV1) 是在初级感觉神经元的 C 纤维和 Ad 纤维上表达的阳离子通道，并被低 pH 值激活。 TRPV1 激活导致炎症介质释放，产生水肿和中性粒细胞浸润。我们之前证明神经源性因素有助于胰腺炎的发病机制。 Resiniferatoxin (RTX) 是一种 TRPV1 激动剂，高剂量时可使 C 纤维和 Ad 纤维去功能化。当我们发现用于 ERCP 的不透射线造影剂溶液的 pH 值为 6.9 时，我们假设低 pH 值可能通过激活 TRPV1 导致造影剂诱发的胰腺炎的发生。大鼠在有或没有 RTX 的情况下接受不同 pH 值的对比溶液的等压胰管注射。注入胰管的造影剂溶液（pH 6.9）导致胰腺水肿、血清淀粉酶、中性粒细胞浸润和组织学损伤显着增加。在等压下注入 pH 7.3 的溶液几乎不会造成损害。注射pH 6.0 的溶液后，胰腺炎的严重程度显着增加。为了确定低 pH 值的影响是否由 TRPV1 介导，将 RTX 添加到对比溶液中。在 pH 值 6.0 和 6.9 时，RTX 显着降低胰腺炎的严重程度。低 pH 对比溶液通过 TRPV1 依赖性机制促进胰腺炎的发生。增加造影剂溶液的 pH 值和/或添加抑制初级感觉神经激活的药物可能会降低 ERCP 后胰腺炎的风险。
Endoscopic retrograde cholangiopancreatography (ERCP) has a high risk of pancreatitis although the underlying mechanisms are unclear. Transient receptor potential vanilloid 1 (TRPV1) is a cation channel expressed on C and Ad fibres of primary sensory neurons and is activated by low pH. TRPV1 activation causes release of inflammatory mediators that produce oedema and neutrophil infiltration. We previously demonstrated that neurogenic factors contribute to the pathogenesis of pancreatitis. Resiniferatoxin (RTX) is a TRPV1 agonist that, in high doses, defunctionalises C and Ad fibres. When we discovered that the pH of radio-opaque contrast solutions used for ERCP was 6.9, we hypothesised that low pH may contribute to the development of contrast-induced pancreatitis via activation of TRPV1. Rats underwent equal pressure pancreatic ductal injection of contrast solutions at varying pH with or without RTX. Contrast solution (pH 6.9) injected into the pancreatic duct caused a significant increase in pancreatic oedema, serum amylase, neutrophil infiltration, and histological damage. Solutions of pH 7.3 injected at equal pressure caused little damage. The severity of the pancreatitis was significantly increased by injection of solutions at pH 6.0. To determine if the effects of low pH were mediated by TRPV1, RTX was added to the contrast solutions. At pH levels of 6.0 and 6.9, RTX significantly reduced the severity of pancreatitis. Contrast solutions with low pH contribute to the development of pancreatitis through a TRPV1-dependent mechanism. It is possible that increasing the pH of contrast solution and/or adding an agent that inhibits primary sensory nerve activation may reduce the risk of post-ERCP pancreatitis.
登录
查看更多内容
影响因子：
2.9
作者：
He, ZJ;Winston, JH;Pasricha, PJ
通讯作者：
Pasricha, PJ
影响因子：
5
作者：
JUNG, DH
通讯作者：
JUNG, DH
影响因子：
7.7
作者：
Manolakopoulos, S;Avgerinos, A;Raptis, SA
通讯作者：
Raptis, SA
DOI：
10.1152/ajpgi.1997.272.4.g785
发表时间：
1997-04-01
影响因子：
4.5
作者：
Figini, M;Emanueli, C;Bunnett, N
通讯作者：
Bunnett, N
影响因子：
29.4
作者：
Nathan, JD;Romac, J;Liddle, RA
通讯作者：
Liddle, RA