Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Am J Gastroenterol. 2010 Sep;105(9):2050-9. doi: 10.1038/ajg.2010.23. Epub 2010 Feb 23.
About 210,000 new cases of acute pancreatitis (AP) involving reversible inflammation of the pancreas are reported in the United States every year. About one-fourth of all patients with AP go on to develop severe acute pancreatitis (SAP), which, unlike uncomplicated or mild acute pancreatitis (MAP, usually a self-limiting disease), constitutes a life-threatening condition with systemic complications, chiefly multiorgan dysfunction. An early prediction of the severity and outcome of patients with acute pancreatitis (AP) can lead to better treatment regimens for patients with SAP. There is currently no established biomarker for the early diagnosis of SAP. In this study, we investigated the potential of serum neutrophil gelatinase-associated lipocalin (NGAL) as an early marker to distinguish severe (SAP) from MAP and examine its ability to predict the prognosis of patients with SAP.
To check the time kinetics of rise in NGAL during AP, we quantified NGAL levels in sera from mice with MAP or SAP at various time points (6, 12, 24 and 48 h) using sandwich enzyme-linked immunosorbent assay. NGAL levels were also quantified in serum from 28 MAP and 16 SAP cases and compared with 28 chronic pancreatitis and 30 healthy control samples. Samples collected within 5 days from onset of symptoms were included. The relationship of NGAL levels with survival and multiorgan failure (MOF) in SAP was also examined.
Although NGAL levels were significantly higher in mice with both MAP and SAP 6 h after induction (compared to control animals), only mice with SAP exhibited a significant increase in NGAL levels at 24 h (P=0.003). NGAL levels declined at 48 h after induction in animals with both MAP and SAP but did not reach baseline levels. Among patients, mean (+/-s.e.) serum NGAL level was significantly higher in SAP (634+/-139 ng/ml) compared to MAP (84.7+/-7 ng/ml, P=0.0001). On subanalysis, the difference between MAP and SAP cases was significant in the first 48 h but not at 72, 96, or 120 h. NGAL was 100%, 96%, 97%, and 84% specific and 100%, 87.5%, 92%, and 94% sensitive in distinguishing SAP from MAP at 48, 72, 96, and 120 h, respectively, after the onset of symptoms. NGAL levels were significantly higher in SAP cases complicated by MOF (P=0.004), and high NGAL levels in SAP appeared to correlate with a fatal outcome.
Our data provide the first evidence for the potential of serum NGAL as an early marker to distinguish MAP from SAP. Further, high NGAL levels predict MOF and fatal outcome in patients with SAP. This study provides sufficient evidence for multi-institutional randomized trials for estimating the potential of NGAL as early biomarker for SAP.
据报道，每年美国约有 21 万例新的急性胰腺炎（AP）病例涉及胰腺可逆性炎症。约四分之一的 AP 患者会发展为重症急性胰腺炎（SAP），与非复杂性或轻度急性胰腺炎（MAP，通常为自限性疾病）不同，SAP 构成了一种危及生命的疾病，伴有全身并发症，主要是多器官功能障碍。对急性胰腺炎（AP）患者严重程度和预后的早期预测可以为 SAP 患者制定更好的治疗方案。目前尚无 SAP 的早期诊断的既定生物标志物。在这项研究中，我们研究了血清中性粒细胞明胶酶相关脂质运载蛋白（NGAL）作为区分重症（SAP）和轻症（MAP）的早期标志物的潜力，并检验其预测 SAP 患者预后的能力。
为了检查 NGAL 在 AP 期间升高的时间动力学，我们使用夹心酶联免疫吸附试验在不同时间点（6、12、24 和 48 小时）定量测定 MAP 或 SAP 小鼠血清中的 NGAL 水平。还在 28 例 MAP 和 16 例 SAP 病例的血清中定量测定了 NGAL 水平，并与 28 例慢性胰腺炎和 30 例健康对照组进行了比较。纳入的样本均来自症状发作后 5 天内。还检查了 NGAL 水平与 SAP 中的存活和多器官衰竭（MOF）的关系。
尽管诱导后 6 小时，MAP 和 SAP 小鼠的 NGAL 水平均显著升高（与对照动物相比），但只有 SAP 小鼠在 24 小时时 NGAL 水平显著升高（P=0.003）。MAP 和 SAP 小鼠在诱导后 48 小时时 NGAL 水平下降，但未恢复至基线水平。在患者中，SAP（634+/-139ng/ml）的血清 NGAL 水平明显高于 MAP（84.7+/-7ng/ml，P=0.0001）。亚分析显示，在 48 小时内，MAP 和 SAP 病例之间的差异具有统计学意义，但在 72、96 和 120 小时时无差异。在症状发作后 48、72、96 和 120 小时，NGAL 分别为 100%、96%、97%和 84%特异性和 100%、87.5%、92%和 94%敏感性，可用于区分 SAP 和 MAP。SAP 合并 MOF 患者的 NGAL 水平明显更高（P=0.004），SAP 中高 NGAL 水平似乎与致命结局相关。
我们的数据首次提供了血清 NGAL 作为区分 MAP 和 SAP 的早期标志物的潜力的证据。此外，SAP 患者中高 NGAL 水平预测 MOF 和致命结局。这项研究为估计 NGAL 作为 SAP 早期生物标志物的潜力的多机构随机试验提供了充分的证据。
