Tian Bing, Ma Chao, Wang Jian, Pan Chun-Shu, Yang Gen-Jin, Lu Jian-Ping
Department of Radiology, Changhai Hospital of Shanghai, The Second Military Medical University, Shanghai 200433, P.R. China.
Pharmaceutical Analysis and Testing Center, School of Pharmacy, The Second Military Medical University, Shanghai 200433, P.R. China.
Mol Med Rep. 2015 Jan;11(1):53-8. doi: 10.3892/mmr.2014.2738. Epub 2014 Oct 22.
Pathological and metabolic alterations co-exist and co-develop in the progression of chronic pancreatitis (CP). The aim of the present study was to investigate the metabolic characteristics and disease severity of a rat model of CP in order to determine associations in the observed pathology and the metabolites of CP using high-resolution magic-angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR). Wistar rats (n=36) were randomly assigned into 6 groups (n=6 per group). CP was established by administering dibutyltin dichloride solution into the tail vein. After 0, 7, 14, 21, 28 and 35 days, the pancreatic tissues were collected for pathological scoring or for HR-MAS NMR. Correlation analyses between the major pathological scores and the integral areas of the major metabolites were determined. The most representative metabolites, aspartate, betaine and fatty acids, were identified as possessing the greatest discriminatory significance. The Spearman's rank correlation coefficients between the pathology and metabolites of the pancreatic tissues were as follows: Betaine and fibrosis, 0.454 (P=0.044); betaine and inflammatory cell infiltration, 0.716 (P=0.0001); aspartate and fibrosis, -0.768 (P=0.0001); aspartate and inflammatory cell infiltration, -0.394 (P=0.085); fatty acid and fibrosis, -0.764 (P=0.0001); and fatty acid and inflammatory cell infiltration, -0.619 (P=0.004). The metabolite betaine positively correlated with fibrosis and inflammatory cell infiltration in CP. In addition, aspartate negatively correlated with fibrosis, but exhibited no significant correlation with inflammatory cell infiltration. Furthermore, the presence of fatty acids negatively correlated with fibrosis and inflammatory cell infiltration in CP. HR-MAS NMR may be used to analyze metabolic characteristics in a rat model of different degrees of chronic pancreatitis.
在慢性胰腺炎(CP)的进展过程中,病理改变和代谢改变同时存在且共同发展。本研究的目的是调查CP大鼠模型的代谢特征和疾病严重程度,以便使用高分辨率魔角旋转核磁共振波谱(HR-MAS NMR)确定观察到的病理学与CP代谢物之间的关联。将36只Wistar大鼠随机分为6组(每组n = 6)。通过将二丁基二氯化锡溶液注入尾静脉建立CP模型。在0、7、14、21、28和35天后,收集胰腺组织进行病理评分或HR-MAS NMR检测。确定主要病理评分与主要代谢物积分面积之间的相关性分析。最具代表性的代谢物,天冬氨酸、甜菜碱和脂肪酸,被确定具有最大的鉴别意义。胰腺组织病理学与代谢物之间的Spearman等级相关系数如下:甜菜碱与纤维化,0.454(P = 0.044);甜菜碱与炎性细胞浸润,0.716(P = 0.0001);天冬氨酸与纤维化,-0.768(P = 0.0001);天冬氨酸与炎性细胞浸润,-0.394(P = 0.085);脂肪酸与纤维化,-0.764(P = 0.0001);脂肪酸与炎性细胞浸润,-0.619(P = 0.004)。代谢物甜菜碱与CP中的纤维化和炎性细胞浸润呈正相关。此外,天冬氨酸与纤维化呈负相关,但与炎性细胞浸润无显著相关性。此外,脂肪酸的存在与CP中的纤维化和炎性细胞浸润呈负相关。HR-MAS NMR可用于分析不同程度慢性胰腺炎大鼠模型的代谢特征。