上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (4): 421-.doi: 10.3969/j.issn.1674-8115.2011.04.008

• 论著（基础研究） • 上一篇    下一篇

艾塞那肽诱发大鼠胰腺组织病变研究

唐华勇, 余 枭, 杨永超, 田步宁, 余 灿   

  1. 中南大学湘雅三医院普外科, 长沙 410013
  • 出版日期:2011-04-28 发布日期:2011-04-28
  • 通讯作者: 余 枭, 电子信箱: yuxiaoyx4@126.com。
  • 作者简介:唐华勇（1981—）, 男, 主治医师, 硕士；电子信箱: tanghuayong1981@126.com|现在湖南中医药高等专科学校附属第一医院普外科工作（412000）。

Preliminary study of exenatide-induced pancreatic tissue injury in rats

TANG Hua-yong, YU Xiao, YANG Yong-chao, TIAN Bu-ning, YU Can   

  1. Department of Abdominal Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China
  • Online:2011-04-28 Published:2011-04-28

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摘要：

目的 探讨艾塞那肽对大鼠胰腺组织的损伤作用。方法 30只SD大鼠随机分为艾塞那肽实验组和空白对照组，每组15只，连续10周分别每日两次皮下注射艾塞那肽5 μg/kg或等量生理盐水。大鼠处死后取下腔静脉血和胰腺组织标本，ELISA 法检测血清淀粉酶、脂肪酶、白介素（IL）-1、IL-6和肿瘤坏死因子（TNF）-α水平及胰腺组织髓过氧化物酶（MOP）含量，计算胰腺干质量/湿质量比，胰腺组织HE染色并行病理学评分，电子显微镜观察胰腺组织超微结构。结果 两组血清淀粉酶、脂肪酶、IL-1、IL-6和TNF-α水平差异无统计学意义（P>0.05）。艾塞那肽实验组胰腺组织MPO含量显著高于空白对照组[（0.24±0.07）U/L和 （0.18±0.05）U/L]（P<0.05），胰腺干质量/湿质量比显著小于空白对照组(0.183±0.049和0.256±0.064) （P<0.05）。HE染色显示，艾塞那肽实验组有5例胰腺组织出现慢性胰腺炎症改变，空白对照组无胰腺炎症性改变。胰腺组织病理学评分显示，除腺体萎缩指标外，两组胰腺组织病变面积、纤维化、炎症和水肿等指标评分差异均有统计学意义（P<0.05）。电子显微镜观察显示，艾塞那肽实验组腺泡细胞内可见核固缩改变、胞质内空泡形成增多、细胞间隙增宽并有炎症细胞浸润，空白对照组未见明显异常变化。结论 长期应用艾塞那肽可引起大鼠慢性胰腺炎症反应而损伤胰腺组织。

关键词: 艾塞那肽, 胰腺炎, 组织病理学, 超微结构

Abstract:

Objective To investigate the pancreatic tissue injury induced by exenatide in rats. Methods Thirty SD rats were randomly divided into exenatide-induced group and blank control group, with 15 rats in each group. Rats in exenatide-induced group were subcutaneously injected with exenatide at the dose of 5 μg/kg twice a day for 10 weeks, and those in blank control group were injected with the same amount of normal saline. Rats were then sacrificed, blood samples were obtained from inferior vena, and pancreatic tissues were harvested. Serum levels of amylase, lipase, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α and contents of myeloperoxidase (MPO) in pancreatic tissues were measured by ELISA, pancreatic wet/dry ratios were calculated, HE staining and histopathological scoring of pancreatic tissues were performed, and microstructure of pancreatic tissues were observed by electron microscopy. Results There was no significant difference in serum levels of amylase, lipase, IL-1, IL-6 and TNF-α between two groups （P>0.05）. The content of MOP in exenatide-induced group was significantly higher than that in blank control group [（0.24±0.07）U/L vs （0.18±0.05）U/L]（P<0.05）, and the pancreatic wet /dry ratio in exenatide-induced group was significantly lower than that in blank control group (0.183±0.049 vs 0.256±0.064) （P<0.05）. HE staining demonstrated that there were 5 pancreatic tissue samples with chronic inflammation in exenatide-induced group, while there were no chronic inflammatory changes in blank control group. Histopathological scoring of pancreatic tissues revealed that except for the parameter of gland atrophy, there were significant differences in the parameters of lesion area, fibrosis, inflammation and edema between two groups （P<0.05）. It was observed by electronic microscopy that there were karyopyknosis, cytoplasmic vacuolization, wide intercellular gap and infiltration of inflammatory cells for pancreatic acinar cells in exenatide-induced group, while there was no obvious abnormality in blank control group. Conclusion Long-term administration of exenatide may lead to chronic pancreatic inflammation and pancreatic tissue injury in rats.

Key words: exenatide, pancreatitis, histopathology, ultrastructure