Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Sci Rep. 2019 Aug 16;9(1):11947. doi: 10.1038/s41598-019-48462-0.
Biliary tract infection (BTI)-derived sepsis remains a serious problem with significant morbidity and mortality in the modern era of critical care management. Current animal models of BTI have relied mostly on injecting purified bacteria or their toxins into the biliary tract. These models do not fully reflect pathophysiology or disease processes of clinical cholangitis or cholecystitis. In the current study, we developed a novel model of BTI by performing cholecystocolonic anastomosis (CCA) in rabbits and characterized pathophysiologic changes in this model. This model is intended to mimic the clinical process of cholecystocolonic fistula with reflux cholangitis, a severe form of BTI. Adult male rabbits were subjected to BTI-derived sepsis through an anastomosis of the gall bladder to the colon (i.e., CCA). The animals were monitored for 7 days to record survival. In additional groups of animals, various bacterial, hemodynamic, histological and biochemical parameters were measured at 12, 24, 48 and 72 h after CCA. The anastomosis between the gallbladder and the colon required about 5-8 min to finish. The median survival time for rabbits after CCA was 96 h. The positive rates of bacterial culture at 72 h after CCA were 83.3% and 100% in the blood and liver, respectively. The most common microorganism was Escherichia coli followed by Enterococcus. Plasma Tumor Necrosis Factor-α (TNF-α), Lnterleukin-10 (IL-10), Lnterleukin-6 (IL-6), and High-mobility group box 1 protein (HMGB-1) levels were greatly elevated after CCA. The cardiac index and heart rate increased slightly at 12 h after CCA and then continued to decrease. Systemic hypotension developed 48 h after CCA. Histological studies showed reflux cholangitis with acute lung and kidney injury. Cholecystocolonic anastomosis produces polymicrobial sepsis in rabbits, which mimics many aspects of human BTI-derived sepsis. It is reproducible and easy to perform and may serve as an excellent model for future sepsis research.
胆道感染（BTI）引起的败血症在现代重症监护管理时代仍然是一个严重的问题，具有显著的发病率和死亡率。目前的 BTI 动物模型主要依赖于将纯化的细菌或其毒素注入胆道。这些模型不能完全反映临床胆管炎或胆囊炎的病理生理学或疾病过程。在本研究中，我们通过在兔子中进行胆囊结肠吻合术（CCA）来开发一种新的 BTI 模型，并对该模型的病理生理变化进行了特征描述。该模型旨在模拟临床胆囊结肠瘘伴反流性胆管炎的过程，这是一种严重的 BTI。成年雄性兔子通过胆囊与结肠吻合术（即 CCA）发生 BTI 源性败血症。监测动物 7 天，记录存活情况。在另外几组动物中，在 CCA 后 12、24、48 和 72 小时测量各种细菌、血流动力学、组织学和生化参数。胆囊与结肠之间的吻合大约需要 5-8 分钟完成。CCA 后兔子的中位存活时间为 96 小时。CCA 后 72 小时血和肝的细菌培养阳性率分别为 83.3%和 100%。最常见的微生物是大肠杆菌，其次是肠球菌。CCA 后血浆肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）、白细胞介素-6（IL-6）和高迁移率族蛋白 1 （HMGB-1）水平显著升高。CCA 后 12 小时心指数和心率略有升高，然后继续下降。48 小时后出现全身性低血压。组织学研究显示反流性胆管炎伴有急性肺和肾损伤。胆囊结肠吻合术在兔子中产生多微生物败血症，模拟了许多人类 BTI 源性败血症的方面。它具有可重复性和易操作性，可能成为未来脓毒症研究的优秀模型。
