右美托咪定通过影响脊髓ERK1和CREB磷酸化改善大鼠肠易激综合征内脏痛

刘亚涛; 刘伟; 王晓庆; 万占海; 孟宁

doi:10.16016/j.2097-0927.202209195

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右美托咪定通过影响脊髓ERK1和CREB磷酸化改善大鼠肠易激综合征内脏痛

基础医学 | 更新时间：2026-01-09

- 右美托咪定通过影响脊髓ERK1和CREB磷酸化改善大鼠肠易激综合征内脏痛
- Dexmedetomidine alleviates chronic functional visceral pain in rats with irritable bowel syndrome through phosphorylation of ERK1 and CREB
- 陆军军医大学学报 2023年45卷第8期页码：801-809
- 作者机构：
  
  1.730000 兰州，兰州大学：第一医院麻醉手术科
  2.730000 兰州，兰州大学：基础医学院病理教研室
- 作者简介：
  
  [刘亚涛；E-mail：doctorliuyt@163.comLIU Yatao, E-mail: doctorliuyt@163.com
- 基金信息：
- DOI：10.16016/j.2097-0927.202209195
  中图分类号： R574.62;R966;R971.3
- 收稿：2022-09-22，
  
  修回：2022-11-15，
  
  纸质出版：2023-04-30
- 稿件说明：
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刘亚涛, 刘伟, 王晓庆, 等. 右美托咪定通过影响脊髓ERK1和CREB磷酸化改善大鼠肠易激综合征内脏痛[J]. 陆军军医大学学报, 2023,45(8):801-809.

Yatao LIU, Wei LIU, Xiaoqing WANG, et al. Dexmedetomidine alleviates chronic functional visceral pain in rats with irritable bowel syndrome through phosphorylation of ERK1 and CREB[J]. Journal of Army Medical University, 2023, 45(8): 801-809.
刘亚涛, 刘伟, 王晓庆, 等. 右美托咪定通过影响脊髓ERK1和CREB磷酸化改善大鼠肠易激综合征内脏痛[J]. 陆军军医大学学报, 2023,45(8):801-809. DOI： 10.16016/j.2097-0927.202209195.

Yatao LIU, Wei LIU, Xiaoqing WANG, et al. Dexmedetomidine alleviates chronic functional visceral pain in rats with irritable bowel syndrome through phosphorylation of ERK1 and CREB[J]. Journal of Army Medical University, 2023, 45(8): 801-809. DOI： 10.16016/j.2097-0927.202209195.

摘要

目的

探讨右美托咪定(Dexmedetomidine，Dex)对肠易激综合征(irritable bowel syndrome，IBS)内脏痛大鼠结肠和脊髓的保护作用，及其对细胞外信号调节蛋白激酶1(extraeellular signal regulated kinase1，ERK1)和环磷腺苷反应元件结合蛋白(cyclic adenosine monophosphate response element binding protein，CREB)磷酸化的影响机制。

方法

将40只SPF级足月雄性SD大鼠(6~8 g)采用结直肠自制球囊扩张(colorectal dilatation，CRD)刺激来构建大鼠IBS模型。动物实验分为正常组、模型组、Dex组、Dex+pc组，模型组、Dex组、Dex+pc组接受CRD刺激，正常组实验动物不做任何处理。造模成功后Dex组动物每日腹腔注射5 μg/kg的盐酸右美托咪定注射液，Dex+pc组动物每日腹腔注射5 μg/kg的盐酸右美托咪定注射液和pc DNA3.1-CREB，正常组、模型组大鼠腹腔注射等剂量的生理盐水和100 nmol/L的pc DNA3.1-CREB-NC。TUNEL染色检测各组大鼠脊髓组织中的细胞凋亡，实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction，RT-qPCR)检测大鼠脊髓组织中ERK1和CREB的mRNA的表达；Western blot检测大鼠脊髓组织中p-ERK1、p-CREB的表达。

结果

与正常组比较，模型组、Dex组、Dex+pc组大鼠脊髓组织中的细胞凋亡率、ERK1和CREB的mRNA的表达、p-ERK1、p-CREB的表达明显升高(

0.05)，与模型组比较，Dex组、Dex+pc组大鼠脊髓组织中的细胞凋亡率、ERK1和CREB的mRNA的表达、p-ERK1、p-CREB的表达明显下降(

0.05)；与Dex组比较，Dex+pc组大鼠脊髓组织中的细胞凋亡率、ERK1和CREB的mRNA的表达、p-ERK1、p-CREB的表达明显升高(

0.05)。

结论

右美托咪定能抑制慢性功能性内脏痛大鼠脊髓组织的细胞凋亡，可能通过抑制ERK1和CREB的磷酸化来发挥结肠和脊髓组织的保护作用。

Abstract

Objective

To investigate the protective effect of Dexmedetomidine (Dex) on the colon and spinal cord of irritable bowel syndrome (IBS) rats with chronic functional visceral pain

and its underlying mechanism of its effects on phosphorylation of extraeellular signal regulated kinase 1 (ERK1) and cyclic adenosine monophosphate response element binding protein (CREB).

Methods

Forty SPF-grade male SD rats (6~8 g) were inflicted with colorectal dilatation (CRD) stimulation to establish a rat model of irritable bowel syndrome (IBS). Then the animals were divided into normal group

model group

Dex group and Dex+pc group. The rats from the normal group do not do any treatment

and those of the model group

Dex group and Dex+pc group received CRD stimulation. After successful modeling

the rats in the Dex group were injected intraperitoneally with 5 μg/kg Dex hydrochloride injection daily

and those in the Dextpc group were injected intraperitoneally with 5 μg/kg Dex hydrochloride daily

as well as pc DNA3.1-CREB. The rats in the control group and model group were injected intraperitoneally with the same dose of normal saline and 100 nmol/L of pc DNA3.1-CREB-NC. TUNEL assay was used to detect cell apoptosis

real-time quantitative polymerase chain reaction (RT-qPCR) was employed to detect the mRNA expression of ERK1 and CREB

and Western blotting was used to detect the expression of p-ERK1 and p-CREB in rat spinal cord tissues.

Results

Compared with the normal group

the cell apoptotic rate

mRNA levels of ERK1 and CREB

and expression of p-ERK1 and p-CREB in spinal cord tissues were significantly increased in the model

Dex and Dex+pc groups (

0.05). The Dex group and Dex+pc group had obviously lower apoptotic rate

decreased ERK1 and

CREB expression at mRNA level

and reduced expression of p-ERK1 and p-CREB than the model group (

0.05). What's more

apoptotic rate

mRNA expression of ERK1 and CREB

and protein expression of p-ERK1 and p-CREB were notably higher in the Dex+pc group than the Dex group (

0.05).

Conclusion

Dex can significantly inhibits the apoptosis in spinal cord tissue of rats with chronic functional visceral pain. It may play a protective role in colon and spinal cord tissues by inhibiting the phosphorylation of ERK1 and CREB.

关键词

Keywords

references

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