Tanoglu Alpaslan, Yazgan Yusuf, Kaplan Mustafa, Berber Ufuk, Kara Muammer, Demırel Dilaver, Ipcioglu Osman Metin
GATA Haydarpasa Training Hospital, Gastroenterology Department, 34668 Uskudar-Istanbul, Turkey.
GATA Haydarpasa Training Hospital, Pathology Department, 34668 Uskudar-Istanbul, Turkey.
Clin Res Hepatol Gastroenterol. 2015 Feb;39(1):145-50. doi: 10.1016/j.clinre.2014.06.003. Epub 2014 Jul 4.
Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are still very limited. We aimed to investigate the efficacy of trimetazidine on cerulein-induced pancreatic apoptosis and histopathological and biochemistrical consequences of acute pancreatitis.
Thirty-two Wistar albino rats were randomized into four groups (group 1: control group; group 2: acute pancreatitis group; group 3: acute pancreatitis and trimetazidine treatment group; group 4: placebo group). Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 μg/kg) four times at one-hour intervals. Trimetazidine was prepared in suspension form. In group 3, after gas anesthesia, trimetazidine was administrated to rats via a catheter. Serum interleukin (IL)-1β, tumor necrosis factor (TNF)-α, amylase, lipase and leukocyte levels, pancreatic apoptotic status and pancreatic Schoenberg scores were determined for all groups. Results are given as the mean ± SD. A value of P<0.05 was accepted as statistically significant. SPSS for Windows v15.0 was used for statistical analyses.
In the acute pancreatitis group IL-1β, amylase, lipase and leukocyte levels were elevated and pancreatic histopathological evaluation revealed a diagnosis of acute pancreatitis IL-1β amylase and lipase levels and pancreatic inflammation were decreased significantly in the trimetazidine group (P<0.01). White blood cell counts and TNF-α concentrations for the trimetazidine group and the acute pancreatitis group were not significantly different. Trimetazidine significantly reduced apoptosis in pancreatic tissues and Schoenberg scores were also significantly reduced (P<0.05).
In this study, we showed that trimetazidine treatment significantly decreases the levels of IL-1β, amylase and lipase reduces pancreatic apoptosis and ameliorates the histopathological findings of cerulein-induced acute pancreatitis. Trimetazidine could be a new therapeutic option in the early treatment of acute pancreatitis.
急性胰腺炎的死亡率和发病率仍然很高,治疗选择仍然非常有限。我们旨在研究曲美他嗪对雨蛙肽诱导的胰腺细胞凋亡以及急性胰腺炎的组织病理学和生物化学后果的疗效。
将32只Wistar白化大鼠随机分为四组(第1组:对照组;第2组:急性胰腺炎组;第3组:急性胰腺炎加曲美他嗪治疗组;第4组:安慰剂组)。通过皮下注射雨蛙肽(20μg/kg),每隔1小时注射4次,诱导急性水肿性胰腺炎。曲美他嗪制成混悬液形式。在第3组中,气体麻醉后,通过导管给大鼠注射曲美他嗪。测定所有组的血清白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α、淀粉酶、脂肪酶和白细胞水平、胰腺细胞凋亡状态以及胰腺Schoenberg评分。结果以平均值±标准差表示。P<0.05的值被认为具有统计学意义。使用Windows v15.0版的SPSS进行统计分析。
急性胰腺炎组的IL-1β、淀粉酶、脂肪酶和白细胞水平升高,胰腺组织病理学评估显示诊断为急性胰腺炎。曲美他嗪组的IL-1β、淀粉酶和脂肪酶水平以及胰腺炎症显著降低(P<0.01)。曲美他嗪组和急性胰腺炎组的白细胞计数和TNF-α浓度无显著差异。曲美他嗪显著降低了胰腺组织中的细胞凋亡,Schoenberg评分也显著降低(P<0.05)。
在本研究中,我们表明曲美他嗪治疗可显著降低IL-1β、淀粉酶和脂肪酶水平,减少胰腺细胞凋亡,并改善雨蛙肽诱导的急性胰腺炎的组织病理学表现。曲美他嗪可能是急性胰腺炎早期治疗的一种新的治疗选择。