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中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (2): 134-139.doi: 10.12092/j.issn.1009-2501.2019.02.003

• 基础研究 • 上一篇    下一篇

地塞米松对小鼠急性胰腺炎胰腺组织中Notch信号及凋亡相关基因表达的影响

孔令宇1,席 錾2,杨亚勤1,马文婷3,吴 畏1,郝同琴1   

  1. 1新乡医学院第一附属医院急诊科,卫辉 453100,河南; 2新乡医学院第一附属医院儿外科,卫辉 453100,河南; 3新乡医学院三全学院诊断学实验室,新乡 453003,河南
  • 收稿日期:2018-11-14 修回日期:2018-12-06 出版日期:2019-02-26 发布日期:2019-03-04
  • 通讯作者: 郝同琴,女,本科,主任医师,研究方向:中毒与危重症。 Tel:13903801685 E-mail: 472206354@qq.com
  • 作者简介:孔令宇,女,硕士,主治医师,研究方向:急危重症。 Tel:18737319877 E-mail: dulala2010@126.com
  • 基金资助:

    2016年河南省组织再生重点实验室开放课题项目(KFKT16003)

Effects of dexamethasone on the Notch signaling pathway and apoptosis-associated genes in acute pancreatitis

KONG Lingyu1, XI Zan2, YANG Yaqin1, MA Wenting3, WU Wei1, HAO Tongqin1   

  1. 1 Department of Emergency, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China; 2 Department of Pediatric surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China;  3 Department of Diagnostic Laboratory of Sanquan College, Xinxiang Medical University, Xinxiang 453003, Henan, China
  • Received:2018-11-14 Revised:2018-12-06 Online:2019-02-26 Published:2019-03-04

摘要:

目的: 探讨地塞米松对急性胰腺炎(acute pancreatitis,AP)小鼠胰腺组织中Notch1,Hes1及凋亡因子Bax、Bcl-2表达的影响。方法: 利用蛙皮素建立小鼠急性胰腺炎动物模型,实验分组为生理盐水组(对照组),模型组(AP组),地塞米松(dexamethasone,DEX)组,利用ELISA法检测各组动物血清中TNF-α, IL-6的含量;利用实时荧光定量PCR(RT-qPCR)检测各组动物胰腺组织中Notch1,Hes1,Bax及Bcl-2 mRNA的表达情况;利用Western blot检测各组胰腺组织中Notch1,Hes1,Bax及Bcl-2蛋白的表达情况。结果: ELISA检测结果显示,与模型组相比较,DEX组动物血清中TNF-α与IL-6的含量显著降低;RT-qPCR与Western blot结果显示,与模型组相比较,DEX组胰腺组织中Notch1,Hes1,Bcl-2 mRNA的表达与蛋白的表达均显著降低,而Bax mRNA的表达与蛋白的表达显著升高。结论: DEX可能通过抑制Notch信号的激活,抑制Notch1与Hes1的表达,进一步抑制抗凋亡的Bcl-2蛋白的作用,促进促凋亡蛋白Bax的表达,促进胰腺腺泡细胞的凋亡,减少胰腺腺泡细胞的坏死,减少炎症因子,如TNF-α与IL-6等的合成与释放。

关键词: 急性胰腺炎, Notch信号通路, 地塞米松, 细胞凋亡

Abstract:

AIM: To explore the effect of dexamethasone on the expression of Notch1,Hes1, Bax and Bcl-2 in pancreas in acute pancreatitis(AP). METHODS: Caerulein was used to set up AP animal model. The experimental groups were the saline group (control group), the model group (AP group) and dexamethasone group (DEX group). The content of TNF-α and IL-6 in serum in each group was detected using ELISA method. RT-qPCR was used to detect expression of Notch1, Hes1, Bax and Bcl-2 mRNA in pancreas in each group. Western blot was used to detect expression of Notch1, Hes1, Bax and Bcl-2 protein in pancreas in each group. RESULTS:The results of ELISA test showed that dexamethasone could significantly reduce the content of TNF-α and IL-6 in serum, comparing with the model group. The RT-qPCR and Western blot results showed that dexamethasone could significantly reduce the expression of Notch1, Hes1, Bcl-2 mRNA and protein in pancreas, but increase the expression of Bax mRNA and protein, as compared with the AP group. CONCLUSION: Dexamethasone could inhibit activation of the Notch signaling pathway, reduce expression of Notch1 and Hes1, further inhibit expression and antiapoptotic effect of Bcl-2 and promote expression and pro-apoptotic effect of Bax, promote apoptosis and reduce necrosis of pancreatic acinar cells, reduce the synthesis and release of TNF-α and IL-6.

Key words: acute pancreatitis, Notch signaling pathway, dexamethasone, apoptosis

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