Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections.
Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections.
复制标题
DOI：
10.1136/gutjnl-2014-308043
复制
发表时间：
2016-01
期刊：
影响因子：
24.5
通讯作者：
Singh VP
中科院分区：
文献类型：
--
作者：
Noel P;Patel K;Durgampudi C;Trivedi RN;de Oliveira C;Crowell MD;Pannala R;Lee K;Brand R;Chennat J;Slivka A;Papachristou GI;Khalid A;Whitcomb DC;DeLany JP;Cline RA;Acharya C;Jaligama D;Murad FM;Yadav D;Navina S;Singh VP
胰腺周围脂肪坏死常发生于坏死性胰腺炎。区分标志物和重症急性胰腺炎（SAP）介质是重要的，因为靶向介质可能会改善预后。我们评估了人类胰腺坏死集合（NC），假性囊肿（PC）和胰腺囊性肿瘤的潜在代理商，并使用胰腺腺泡，外周血单核细胞（PBMC）和急性胰腺炎（AP）模型，以确定SAP介质。我们测量了由NC和PC中增加的药剂诱导的腺泡和PBMC损伤。在瘦大鼠中研究了白细胞介素（IL）-1β和角质形成细胞趋化因子/生长调节癌基因，三油酸甘油酯单独或与脂肪酶抑制剂奥利司他联合给药的雨蛙样胰腺炎结局。与其他液体相比，NC具有更高的脂肪酸、IL-8和IL-1β。不饱和甘油三酯的脂解和由此产生的不饱和脂肪酸（乌法）、油酸和亚油酸在不到NC中浓度的一半的浓度下诱导坏死性细胞凋亡，但其他药剂在超过这些浓度的两倍时不这样做。细胞因子联合给药导致胰腺和肺部炎症比单独雨蛙肽更高，但只有三油酸甘油酯联合给药导致胰周脂肪搁浅，更高的细胞因子，UFA，多系统器官衰竭（MSOF）和97%的动物死亡率，这是由奥利司他预防。UFA、IL-1β和IL-8在NC中升高。然而，通过胰周脂肪分解产生的UFA导致更严重的炎症和MSOF，将轻度AP转化为SAP。
Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.