Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Sci Rep. 2019 Jan 11;9(1):69. doi: 10.1038/s41598-018-36266-7.
Obesity may aggravate acute pancreatitis (AP) through damaging the intestinal mucosal barrier (IMB). The underlying mechanism remains unclear. This study was aimed to provide further data to clarify the mechanism. 48 rats were divided into 4 groups: 1) normal control (NC), chow-fed rats with sham operation, 2) no-obese rats with AP (NAP), chow-fed rats with taurocholate infusion, 3) obese control (OC), high-fat diet (HFD)-fed rats with sham operation, and 4) obese rats with AP (OAP), HFD-fed rats with taurocholate infusion. Pancreatic pathologic score (11.39 ± 1.76 vs. 14.11 ± 1.05, p = 0.005), intestinal permeability to FD4 (0.91 ± 0.25 μg/ml vs. 7.06 ± 3.67 μg/ml, p < 0.001), serum leptin (10.25 ± 5.59 ng/ml vs. 79.73 ± 38.44 ng/ml, p < 0.001) and ileal apoptosis (2.05 ± 0.73% vs. 4.53 ± 2.28%, p = 0.006) were significantly higher in OAP than in NAP group. The intestinal bacterial richness (Chao 1 and OTUs) was significantly lower in OAP than in NAP rats. The higher abundance of Proteobacteria and reduced proportions of intestinal Actinobacteria, Allobaculum and Barnesiella were detected in OAP group. Obesity may result in decreased intestinal leptin/ObR-b binding, distinct phylogenetic clusters of ileal bacterial communities, increased intestinal inflammatory injury and the insufficient intestinal epithelial cells proliferation during AP attack. Pancreatic injury was aggravated due to obesity associated dysfunction of IMB.
肥胖可能通过损害肠道黏膜屏障(IMB)加重急性胰腺炎(AP)。其潜在机制尚不清楚。本研究旨在提供进一步的数据来阐明该机制。将 48 只大鼠分为 4 组:1)正常对照组(NC),给予标准饮食和假手术;2)非肥胖性 AP 大鼠(NAP),给予标准饮食和牛磺胆酸钠输注;3)肥胖对照组(OC),给予高脂肪饮食和假手术;4)肥胖性 AP 大鼠(OAP),给予高脂肪饮食和牛磺胆酸钠输注。与 NAP 组相比,OAP 组大鼠胰腺病理评分(11.39±1.76 比 14.11±1.05,p=0.005)、肠道对 FD4 的通透性(0.91±0.25μg/ml 比 7.06±3.67μg/ml,p<0.001)、血清瘦素(10.25±5.59ng/ml 比 79.73±38.44ng/ml,p<0.001)和回肠细胞凋亡(2.05±0.73%比 4.53±2.28%,p=0.006)显著更高。OAP 组大鼠肠道细菌丰富度(Chao1 和 OTUs)明显低于 NAP 组。OAP 组大鼠肠道变形菌门丰度较高,厚壁菌门、放线菌门、Allobaculum 和 Barnesiella 的比例减少。在 AP 攻击时,肥胖可能导致肠道瘦素/ObR-b 结合减少、回肠细菌群落的分类簇明显不同、肠道炎症损伤增加和肠上皮细胞增殖不足。由于肥胖相关的 IMB 功能障碍,胰腺损伤加重。