十二指肠空肠旁路术对ZDF大鼠BP肠袢部位炎症状态的改善作用及其机制

doi:10.13481/j.1671-587x.20170616

吉林大学学报(医学版) ›› 2017, Vol. 43 ›› Issue (06): 1155-1160.doi: 10.13481/j.1671-587x.20170616

十二指肠空肠旁路术对ZDF大鼠BP肠袢部位炎症状态的改善作用及其机制

霍连广¹, 严庆涛², 严晶月^1,2, 李娜¹, 苏寒¹, 张美家¹, 毛淑梅¹, 高志芹¹, 曲梅花¹

1. 潍坊医学院药理学教研室应用药理学山东省高校重点实验室, 山东潍坊 261053;
2. 山东省潍坊市人民医院小儿外科, 山东潍坊 261041

收稿日期:2017-06-20 出版日期:2017-11-28 发布日期:2017-12-01
通讯作者: 曲梅花,教授,硕士研究生导师(Tel:0536-8462466,E-mail:qumeihua2016@163.com) E-mail:qumeihua2016@163.com
作者简介:霍连广(1991-),男,山东省临沂市人,医学硕士,主要从事内分泌与代谢方面的研究。
基金资助:
国家自然科学基金课题（31671208）；山东省科技厅自然基金资助课题（ZR2015HL128）

Improvement effect of duodenal-jejunal bypass on inflammatory status of biliopancreatic limb of ZDF rats and its mechanism

HUO Lianguang¹, YAN Qingtao², YAN Jingyue^1,2, LI Na¹, SU Han¹, ZHANG Meijia¹, MAO Shumei¹, GAO Zhiqin¹, QU Meihua¹

1. Department of Pharmacology, Weifang Medical University, Key Lab of Applied Pharmacology in Universities of Shandong, Weifang 261053, China;
2. Department of Pediatric Surgery, Weifang People's Hospital, Shandong Province, Weifang 261041, China

Received:2017-06-20 Online:2017-11-28 Published:2017-12-01

摘要/Abstract

摘要： 目的：探讨十二指肠空肠旁路术（DJB）对肥胖型2型糖尿病（T2DM）大鼠血糖稳态、胰岛素抵抗及炎症的改善作用，阐明其可能机制。方法：20只ZDF大鼠随机分为DJB组和假手术组，每组10只。每组存活8只大鼠。分别在手术前1周和手术后2、4、6周采用罗氏血糖仪测定2组大鼠空腹血糖（FBG）水平，ELISA法检测大鼠血清胰岛素水平，计算大鼠胰岛素敏感指数（HOMA-ISI）和胰岛素抵抗指数（HOMA-IR）。手术后6周处死大鼠，HE染色观察大鼠BP肠袢炎性细胞形态表现，免疫组织学法观察大鼠BP肠袢中AMPK和pAMPK mRNA表达水平，QRT-PCR法检测大鼠炎症相关因子白细胞介素1β（IL-1β）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）、核因子κB （NF-κB）和白细胞介素10（IL-10） mRNA表达水平。结果：与术前比较，术后2周开始DJB组大鼠FBG水平明显降低（t=3.798，P<0.05）；与假手术组比较，DJB组大鼠FBG水平也明显降低（t=3.205，P<0.05）。术后6周，与假手术组比较，DJB组大鼠术后HOMA-IR明显降低（t=4.441，P<0.05），HOMA-ISI明显升高（t=-8.65，P<0.05）。HE染色，与假手术组比较，DJB组大鼠BP肠袢肠管炎性细胞形态明显改善。QRT-PCR法检测，与假手术组比较，DJB组大鼠BP肠袢中促炎性因子IL-1β、IL-6、TNF-α和NF-κB表达水平明显降低（P<0.05），而抗炎性因子IL-10表达水平明显升高（P<0.05）。免疫组织化学检测，与假手术组比较，DJB组大鼠BP肠袢中AMPK及pAMPK表达水平明显升高（P<0.05）。结论：DJB可明显改善T2DM大鼠血糖稳态及胰岛素抵抗，其机制可能与DJB改善T2DM大鼠BP肠袢的炎症状态、调控炎症因子的表达和活化AMPK分子有关。

关键词: 十二指肠空肠旁路术, 2型糖尿病, 炎症, 血糖稳态, 胰岛素抵抗

Abstract: Objective:To investigate the improvement effects of duodenal-jejunal bypass (DJB) on the blood glucose homeostasis, insulin resistance and inflammation of the obese type 2 diabetic(T2DM) ZDF rats, and to discuss its possible mechanism. Methods:A total of 20 ZDF rats were randomly divided into DJB operation group and sham operation group (n=10). There were 8 rats survived in each group after operation. The level of blood glucose (FBG) was detected by Roche glucose meter at 1 week before operation, 2 weeks, 4 weeks and 6 weeks after operation; the fasting serum insulin level of the rats was measured by ELISA kit; the insulin sensitivity index (HOMA-ISI) and insulin resistance index (HOMA-IR) were calculated. The rats were executed 6 weeks after operation. HE staining was used to observe the morphology of the inflammatory cells in BP limb of the rats; the expression levels of AMPK and pAMPK in BP lamb of the rats were observed by immunohistochemical staining;the expression levels of interleukin 1β (IL-1β), interleukin 6(IL-6), tumor necrosis factor α (TNF-α), nuclear factor κB (NF-κB), and interleukin 10 (IL-10) mRNA of the rats were detected by QRT-PCR method. Results:From the 2nd week after operation,compared with before operation,the FBG levels of the rats in DJB operation group were decreased(t=3.798, P<0.05);compared with sham operation group,the FBG level of the rats in DJB operation group was decreased (t=3.205, P<0.05). Six weeks after operation, compared with sham operation group, the HOMA-IR of the rats in DJB operation group was significantly decreased (t=4.441, P<0.05) and the HOMA-ISI was significantly increased (t=-8.65, P<0.05).The HE staining results showed that compared with sham operation group, the morphology of the inflammatory cells in BP limb of the rats in DJB operation group was significantly improved.The QRT-PCR results showed that the expression levels of IL-1β, IL-6, TNF-α and NF-κB of the rats in DJB operation group was significantly decreased compared with sham operation group (P<0.05), while the expression level of IL-10 was significantly increased(P<0.05). The immunohistochemical test results showed that the expression levels of AMPK and pAMPK in BP lamb of the rats in DJB operation group were increased compared with sham operation group. Conclusion:DJB can significantly improve the blood glucose homeostasis and insulin resistance in the T2DM rats, and its mechanism may be related to the decreased expressions of inflammatory factors and the activation of AMPK molecules in BP lamb of the T2DM rats.

Key words: duodenal-jejunal bypass, insulin resistance, type 2 diabetes, inflammation, blood glucose homeostasis

中图分类号:

R587.1

霍连广, 严庆涛, 严晶月, 李娜, 苏寒, 张美家, 毛淑梅, 高志芹, 曲梅花. 十二指肠空肠旁路术对ZDF大鼠BP肠袢部位炎症状态的改善作用及其机制[J]. 吉林大学学报(医学版), 2017, 43(06): 1155-1160.

HUO Lianguang, YAN Qingtao, YAN Jingyue, LI Na, SU Han, ZHANG Meijia, MAO Shumei, GAO Zhiqin, QU Meihua. Improvement effect of duodenal-jejunal bypass on inflammatory status of biliopancreatic limb of ZDF rats and its mechanism[J]. Journal of Jilin University Medicine Edition, 2017, 43(06): 1155-1160.

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十二指肠空肠旁路术对ZDF大鼠BP肠袢部位炎症状态的改善作用及其机制

Improvement effect of duodenal-jejunal bypass on inflammatory status of biliopancreatic limb of ZDF rats and its mechanism

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