Li Wei-Dong, Jia Lin, Ou Ya, Huang Yao-Xing, Jiang Shu-Man
Department of Gastroenterology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China ; Department of Gastroenterology, Guangzhou Nansha Central Hospital, Guangzhou, Guangdong Province, China.
PLoS One. 2013 Nov 14;8(11):e78975. doi: 10.1371/journal.pone.0078975. eCollection 2013.
To monitor intra-abdominal pressure (IAP) and intestinal barrier function in a rat model of acute necrotizing pancreatitis (ANP) to elucidate a potential relevant therapeutic window.
Sprague-Dawley rats were randomly divided into experimental or control groups. The ANP group (n = 40) was injected with 4.5% sodium taurocholate into the pancreatic duct to induce ANP. The controls received only abdominal opening surgery (sham-operated, SO; n = 40) or no treatment or surgery (baseline; 0 h, n = 20). The SO and ANP groups were then randomly subdivided into 3, 6, 12 and 24 h groups (n = 10 each). IAP was measured at each time point and the rats were sacrificed to measure the weight of accumulated ascites fluid and the amylase, endogenous creatinine (Cr), total bilirubin (TB), tumor necrosis factor- alpha (TNF-alpha), diamine oxidase (DAO), and D-lactate. Mortality and the development of pathological changes in the pancreas and intestines were also monitored.
IAP showed a continuous upward trend in the ANP group, with values 2 to 3 times higher than those in the SO group at the corresponding time points and the rising rate was peaking at 6 h. The levels of plasma amylase, TNF-alpha, Cr, TB, DAO, and D-lactate also gradually increased in the ANP group over time and were significantly higher than in the SO group at 3, 6, 12 and 24 h (all P<0.05). Moreover, the rising rate of TNF-alpha, DAO, and D-lactate also peaked at 6 h.
The ANP-induced changes in IAP, inflammatory factors and intestinal barrier that we observed in the rat model were especially obvious at 6 h post-induction, suggesting an early therapeutic window for the treatment of ANP in humans.
在急性坏死性胰腺炎（ANP）大鼠模型中监测腹内压（IAP）和肠屏障功能，以阐明潜在的相关治疗窗。
将Sprague-Dawley大鼠随机分为实验组或对照组。ANP组（n = 40）经胰管注射4.5%牛磺胆酸钠诱导ANP。对照组仅接受开腹手术（假手术，SO；n = 40）或不接受治疗及手术（基线；0小时，n = 20）。然后将SO组和ANP组随机再分为3、6、12和24小时组（每组n = 10）。在每个时间点测量IAP，并处死大鼠以测量腹水积聚重量以及淀粉酶、内生肌酐（Cr）、总胆红素（TB）、肿瘤坏死因子-α（TNF-α）、二胺氧化酶（DAO）和D-乳酸。还监测死亡率以及胰腺和肠道病理变化的发生情况。
ANP组IAP呈持续上升趋势，相应时间点的值比SO组高2至3倍，上升速率在6小时达到峰值。ANP组血浆淀粉酶、TNF-α、Cr、TB、DAO和D-乳酸水平也随时间逐渐升高，在3、6、12和24小时时显著高于SO组（均P<0.05）。此外，TNF-α、DAO和D-乳酸的上升速率也在6小时达到峰值。
我们在大鼠模型中观察到ANP诱导的IAP、炎症因子和肠屏障变化在诱导后6小时尤为明显，提示人类ANP治疗存在早期治疗窗。
