Özkardeş Alper Bilal, Bozkurt Birkan, Dumlu Ersin Gürkan, Tokaç Mehmet, Yazgan Aylin Kılıç, Ergin Merve, Erel Özcan, Kılıç Mehmet
Clinic of General Surgery, Atatürk Training and Research Hospital, Ankara, Turkey.
Clinic of Pathology, Atatürk Training and Research Hospital, Ankara, Turkey.
Ulus Cerrahi Derg. 2015 Dec 1;31(4):185-91. doi: 10.5152/UCD.2015.3170. eCollection 2015.
To analyze the biochemical and histopathological effects of everolimus in an experimental rat model of cerulein-induced acute pancreatitis. The aim of the present study was to determine the effects of everolimus on blood biochemical parameters and tissue histopathology in an experimental rat model of cerulein-induced acute pancreatitis.
In 30 Wistar albino rats (male; 240-260 g), acute pancreatitis was induced by an intraperitoneal injection of cerulein (50 μg/kg) administered twice in 2 h. They were equally divided into the following three groups: 0.9% isotonic solution (Group 1; control), everolimus once (Group 2), and everolimus twice (Group 3) by oral gavage after cerulein injection. Thirty hours after the induction of pancreatitis, blood samples were collected by direct intracardiac puncture, rats were sacrificed, and pancreatic tissue samples were obtained.
Biochemical analyses of the blood samples showed statistically significant difference in red blood cell count as well as hemoglobin, hematocrit, urea, and alanine transaminase levels among the study groups (p<0.05 in all). Everolimus proved to significantly increase red blood cell count in a dose-independent manner. Hemoglobin and hematocrit levels significantly increased only after treatment with one dose of everolimus. Urea level was significantly different between the Groups 2 and 3; however, no change was observed in both groups when compared with the control. Alanine transaminase level significantly decreased only after treatment with two doses of everolimus. Histopathological analyses revealed that everolimus significantly decreased inflammation and perivascular infiltrate in a dose-dependent manner (35% in Group 2, 75% in Group 3; p=0.048).
Treatment with two doses of everolimus improved some biochemical and histopathological parameters of experimental rat models of cerulein-induced acute pancreatitis and implied the specific inhibition of inflammatory response pathways.
分析依维莫司在雨蛙肽诱导的急性胰腺炎实验大鼠模型中的生化及组织病理学效应。本研究旨在确定依维莫司对雨蛙肽诱导的急性胰腺炎实验大鼠模型血液生化参数及组织病理学的影响。
选取30只雄性Wistar白化大鼠(体重240 - 260 g),通过在2小时内腹腔注射两次雨蛙肽(50 μg/kg)诱导急性胰腺炎。将它们平均分为以下三组:0.9%等渗溶液组(第1组;对照组)、雨蛙肽注射后经口灌胃给予一次依维莫司组(第2组)和给予两次依维莫司组(第3组)。胰腺炎诱导30小时后,通过直接心脏穿刺采集血样,处死大鼠并获取胰腺组织样本。
血样的生化分析显示,各研究组之间红细胞计数以及血红蛋白、血细胞比容、尿素和丙氨酸转氨酶水平存在统计学显著差异(均p<0.05)。依维莫司被证明以剂量非依赖性方式显著增加红细胞计数。仅在给予一剂依维莫司治疗后,血红蛋白和血细胞比容水平显著升高。第2组和第3组之间尿素水平存在显著差异;然而,与对照组相比,两组均未观察到变化。仅在给予两剂依维莫司治疗后,丙氨酸转氨酶水平显著降低。组织病理学分析显示,依维莫司以剂量依赖性方式显著减少炎症和血管周围浸润(第2组为35%,第3组为75%;p = 0.048)。
给予两剂依维莫司可改善雨蛙肽诱导的急性胰腺炎实验大鼠模型的一些生化和组织病理学参数,并提示对炎症反应途径有特异性抑制作用。