Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
J Surg Res. 2013 Apr;180(2):e83-90. doi: 10.1016/j.jss.2012.03.061. Epub 2012 Apr 17.
Therapy for systemic complications in severe necrotizing pancreatitis remains symptomatic owing to the unavailability of more specific therapeutic targets. We investigated the differential gene expression in typically affected organs in a mouse model of severe necrotizing pancreatitis.
Acute necrotizing pancreatitis was induced in mice by retrograde infusion of taurocholate into the common bile duct. Microarray hybridization was subsequently performed with mRNA isolated from the spleen, liver, intestine, and lungs. Additionally, quantitative real-time polymerase chain reaction was performed to confirm the microarray results.
Severe necrotizing pancreatitis induced widespread changes in gene expression, affecting 27.20% of the genes tested in the spleen and 29.07% in the liver. Fewer genes were differentially regulated in the intestine (10.28%) and the lungs (10.75%). Only 10 genes were found to be upregulated in all 4 organs using microarray analysis. This upregulation in all organs was confirmed by quantitative real-time polymerase chain reaction for only 3 molecules. These molecules were lipocalin 2, insulin-like growth factor binding protein 1, and CD14. Additionally we observed significantly aberrant gene regulation of inter-α-trypsin inhibitor family members in several organs.
Differential gene regulation in severe necrotizing pancreatitis is far more organ specific than anticipated, with only 3 molecules uniformly regulated systemically. The inter-α-trypsin inhibitor family of molecules appears to play a crucial biologic role in the systemic inflammatory response in acute pancreatitis. Finally, owing to its regulation and function, α1-microglobulin (or bikunin) may be a suitable predictive marker of the systemic inflammatory response syndrome in acute pancreatitis.
由于缺乏更具体的治疗靶点，严重坏死性胰腺炎的全身并发症的治疗仍然是对症治疗。我们研究了严重坏死性胰腺炎小鼠模型中典型受累器官的差异基因表达。
通过逆行向胆总管内输注牛磺胆酸钠诱导急性坏死性胰腺炎。随后用从脾、肝、肠和肺中分离的 mRNA 进行微阵列杂交。此外，还进行了定量实时聚合酶链反应以确认微阵列结果。
严重坏死性胰腺炎诱导了广泛的基因表达变化，影响了脾脏中 27.20%和肝脏中 29.07%的测试基因。肠道（10.28%）和肺部（10.75%）的基因调节较少。使用微阵列分析仅发现 10 个基因在所有 4 个器官中均上调。这一上调在所有器官中都被定量实时聚合酶链反应证实，只有 3 种分子。这些分子是脂联素 2、胰岛素样生长因子结合蛋白 1 和 CD14。此外，我们还观察到几种器官中α1-抗胰蛋白酶抑制剂家族成员的基因调节明显异常。
严重坏死性胰腺炎的差异基因调节比预期的更具器官特异性，只有 3 种分子系统地受到调节。α1-抗胰蛋白酶抑制剂家族的分子似乎在急性胰腺炎的全身炎症反应中发挥着至关重要的生物学作用。最后，由于其调节和功能，α1-微球蛋白（或 bikunin）可能是急性胰腺炎全身炎症反应综合征的一个合适的预测标志物。
