Marotta F, Barreto R, Wu C C, Naito Y, Gelosa F, Lorenzetti A, Yoshioka M, Fesce E
Hepato-Gastroenterology Department, S. Giuseppe Hospital, Milan, Italy.
Chin J Dig Dis. 2005;6(4):193-7. doi: 10.1111/j.1443-9573.2005.00230.x.
The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion.
Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis.
Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage.
Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.
本研究旨在测试新型合生元或甲硝唑对酒精性急性胰腺炎过程中内毒素血症或肝损伤严重程度的肠道调节作用。
通过胃管给Sprague-Dawley大鼠喂食液体饮食1周，饮食如下：（i）每天3次，每次1 mL合生元混合物（嗜酸乳杆菌、瑞士乳杆菌和双歧杆菌在富集培养基中）；（ii）每天3次，每次20 mg/kg甲硝唑；或（iii）标准饮食。然后，用雨蛙素诱导急性胰腺炎，当疾病发展到成熟阶段时，给大鼠喂食富含酒精的饮食。合生元和甲硝唑治疗再持续2周。在治疗前、6小时后、24小时后以及2周后（大鼠处死时）测量转氨酶和内毒素血症水平。获取肝脏样本进行组织学分析。
合生元而非甲硝唑改善了急性胰腺炎诱导的内毒素血症和转氨酶水平升高。在合生元治疗组中，添加酒精在一定程度上使这些变量恶化，而甲硝唑对肝损伤有负面影响。
用合生元对肠道菌群进行预处理能够有效预防急性胰腺炎及同时大量饮酒过程中的内毒素/细菌移位以及肝损伤。合生元对肝脏组织学的有益作用似乎与内毒素血症相关。甲硝唑未产生这种有益作用；事实上，在持续急性胰腺炎炎症背景下添加酒精时，它会进一步加重肝损伤。
