大鼠急性坏死性胰腺炎和慢性胰腺炎代谢特征分析

Metabolic features of acute necrotizing pancreatitis and chronic pancreatitis

目的用代谢组学方法研究大鼠胰腺组织代谢特征，以期发现胰腺炎症的标记性代谢物。方法Wistar大鼠22只，按数字表法随机分成急性坏死性胰腺炎组（ANP，7只）、慢性胰腺炎组（CP，6只）和对照组（9只）。ANP组经腹腔注射20％L-精氨酸溶液制模；CP组经尾静脉注射二丁基二氯基锡（DBTC）溶液制模；对照组注射等量生理盐水。检测血清淀粉酶含量，胰腺组织行病理学检查。利用高分辨魔角旋转核磁共振波谱对离体胰腺组织进行代谢成分分析，并对实验数据进行主成分分析，比较ANP与CP的代谢特征。结果与对照组相比，ANP组小分子代谢物亮氨酸、异亮氨酸、缬氨酸含量增加，而CP组这些代谢物含量减少。ANP组和CP组的磷酸胆碱、甘油磷酸胆碱、胆碱含量均升高，脂肪酸、乳酸、甜菜碱、甘氨酸含量均下降，CP组中脂类代谢产物含量明显高于ANP组，且仅在CP组中观察到牛磺酸含量升高。结论胰腺炎症疾病造成胰腺组织内代谢异常，升高的牛磺酸水平可能是区分CP和ANP的标记物。

Objective To study the metabolite features of acute necrotizing pancreatitis （ANP） and chronic pancreatitis （CP） in rats. Methods A total of 22 Wistar rats were divided into ANP group （n =7）, CP group （n = 6） and the control group （n = 9）. ANP model was induced peritoneous injection of 20% L- arginine, and the rats were sacrificed 12 hours later. CP model was induced by intravenously injection of DBTC （8 mg/kg body weight）, and the rats were sacrificed after 2 months. The rats in the control group received same amount of saline. Serum amylase was determined and pancreatic tissues were pathologically examined. Metabolic changes of pancreatic tissues in vitro were studied by high resolution magic angle spinning nuclear magnetic resonance （MAS NMR ）, and analyzed by using principal components analysis （PCA）. Characteristic metabolites of ANP and CP were compared. Results Compared with the control group, increased leucine, iso-leucine and valine levels were observed in ANP group, however, the opposite trends were observed in CP group. Phosphocholine, glycerophosphocholine, choline levels were increased and fatty acids, lactate, betaine, glycine levels were decreased in both ANP and CP groups. The lipid content in CP group were significantly higher than that in ANP group and the increased taurine was only observed in CP group. Conclusions There were obvious metabolic features in pancreatic tissue in rats with pancreatitis disorders, and the increased taurine could be used as biomarker to discriminate ANP and CP.