Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis.
Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis.
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DOI：
10.1016/j.jcmgh.2016.08.006
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发表时间：
2017-01
影响因子：
7.2
通讯作者：
Husain SZ
中科院分区：
文献类型：
--
作者：
Orabi AI;Wen L;Javed TA;Le T;Guo P;Sanker S;Ricks D;Boggs K;Eisses JF;Castro C;Xiao X;Prasadan K;Esni F;Gittes GK;Husain SZ
目前迫切需要开发有效的预防性治疗内镜逆行胰胆管造影术后胰腺炎（PEP）。我们发现，早期PEP事件是通过钙激活磷酸酶钙调神经磷酸酶诱导的，并且整体钙调神经磷酸酶缺失废除了小鼠中的PEP。一个关键的问题是腺泡细胞钙调神经磷酸酶是否控制体内PEP的启动。我们使用PEP的小鼠模型，并检查体内腺泡细胞特异性钙调神经磷酸酶缺失的影响，无论是产生一个条件性敲除线或注入一种新的腺相关病毒胰腺弹性蛋白酶改善Cre（I-iCre）到胰管的钙调神经磷酸酶floxed线。我们发现PEP在体内依赖于腺泡细胞钙调神经磷酸酶，这使我们确定钙调神经磷酸酶抑制剂，注入放射造影剂，在很大程度上可以防止PEP。这些结果为开展临床试验以测试导管内钙调磷酸酶抑制剂预防PEP的功效提供了动力。
There is a pressing need to develop effective preventative therapies for post–endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We showed that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEP in vivo. We used a mouse model of PEP and examined the effects of in vivo acinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel adeno-associated virus–pancreatic elastase improved Cre (I–iCre) into the pancreatic duct of a calcineurin floxed line. We found that PEP is dependent on acinar cell calcineurin in vivo, and this led us to determine that calcineurin inhibitors, infused within the radiocontrast, largely can prevent PEP. These results provide the impetus for launching clinical trials to test the efficacy of intraductal calcineurin inhibitors to prevent PEP.