[1]游扬,杨歆,常杏,等.腺苷酸活化蛋白激酶在重症急性胰腺炎大鼠肠黏膜屏障损伤机制中的作用[J].第三军医大学学报,2016,38(09):975-981.
 You Yang,Yang Xin,Chang Xing,et al.AMP-activated protein kinase deteriorates intestinal tight junction damage in rats with severe acute pancreatitis[J].J Third Mil Med Univ,2016,38(09):975-981.
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腺苷酸活化蛋白激酶在重症急性胰腺炎大鼠肠黏膜屏障损伤机制中的作用(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第09期
页码:
975-981
栏目:
基础医学
出版日期:
2016-05-15

文章信息/Info

Title:
AMP-activated protein kinase deteriorates intestinal tight junction damage in rats with severe acute pancreatitis
作者:
游扬杨歆常杏邓盛瑜李静杨仕明凌贤龙
第三军医大学新桥医院消化内科
Author(s):
You Yang Yang Xin Chang Xing Deng Shengyu Li Jing Yang Shiming Ling Xianlong

Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

关键词:
重症急性胰腺炎腺苷酸活化蛋白激酶肠屏障occludin紧密连接
Keywords:
severe acute pancreatitis adenosine monophosphate activated protein kinase intestinal barrier occludin tight junction
分类号:
R-332; R574.502; R576.06
文献标志码:
A
摘要:

目的      探讨腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)在重症急性胰腺炎SD大鼠肠道紧密连接损伤中的作用。      方法       给予SD大鼠腹腔注射不同剂量的20% L-精氨酸溶液,分别制备大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)及轻症急性胰腺炎(mild acute pancreatitis,MAP)模型,通过检测血清淀粉酶水平、胰腺病理改变以证实胰腺炎模型构建成功。对SAP大鼠分别给予AMPK抑制剂Compound C和谷氨酰胺灌胃处理,小肠组织切片染色观察大鼠小肠组织损伤情况;FITC-Dextran通透实验检测肠道通透性;免疫组化和Western blot方法分别检测肠黏膜细胞αSNAP、AMPK和紧密连接蛋白occludin的表达情况。      结果       病理切片证实胰腺炎模型构建成功,并且抑制AMPK后明显降低重症急性胰腺炎的病理损伤;SAP大鼠肠黏膜损伤明显,而加入AMPK抑制剂Compound C或肠黏膜保护剂谷氨酰胺可明显抑制SAP大鼠肠黏膜损伤;SAP组建模48 h(410.25±7.80)的肠道通透性相对于对照组(0.51±0.61)显著增强(P<0.05),而加入AMPK抑制剂Compound C 48 h的Com组(372.95±9.33)或肠黏膜保护剂谷氨酰胺的Gln组(367.93±18.90)(P<0.05),可明显降低SAP大鼠肠道通透性;重症急性胰腺炎时,αSNAP表达下调(P<0.05),而AMPK表达明显增强(P<0.05),加入AMPK抑制剂可以明显上调occludin的表达(P<0.01),提示AMPK对occludin蛋白存在负性调控。       结论       AMPK信号在大鼠重症急性胰腺炎肠黏膜损伤中过度活化,可通过负性调控occludin蛋白的表达导致肠黏膜损伤,从而促进肠黏膜通透性增强。

Abstract:

Objective      To determine of the role of AMP-activated protein kinase (AMPK) in the damage of intestinal tight junction in the rats with severe acute pancreatitis.       Methods      The models of mild (MAP) and severe acute pancreatitis (SAP) were prepared by intraperitoneal injection of different doses of L-arginine solution (20%) to SD rats respectively, and then the models were confirmed by detection of serum amylase level and pathological changes of pancreatic tissues. The SAP rats were treated with the AMPK inhibitor, compound C, and glutamine respectively by gavage. The damages of small intestine mucosa were examined by pathological staining, and the intestinal permeability was measured by FITC-Dextran permeability assay. The expression of αSNAP, AMPK and tight junction protein (occludin) were detected by immunohistochemical assay and Western blot analysis.       Results      The rat models of MAP and SAP were successfully prepared, and inhibition of AMPK significantly attenuated the pathological changes of pancreatic tissues. Significant damage of small intestinal mucosa was observed in SAP rats, while compound C or glutamine markedly alleviated these damages. The intestinal permeability was significantly stronger in the SAP rats in 48 h after model establishment when compared to the control group (410.25±7.80 vs 0.51±0.61, P<0.05), while AMPK inhibitor, compound C (372.95±9.33) or glutamine (367.93±18.90) significantly inhibited the increased intestinal permeability in SAP rats (P<0.05). In SAP rats, the expression level of αSNAP was decreased (P<0.05), while that of AMPK was increased obviously (P<0.05). Inhibition of AMPK greatly enhanced the expression of occludin (P<0.05), suggesting a negative regulation between AMPK and occludin.       Conclusion      AMPK signal is over-activated in the damage of intestinal mucosa in SAP rats, and exerts negative modulation on occludin to induce the damage, and thus leads to increased intestinal permeability.

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更新日期/Last Update: 2016-04-29