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海马 AMPAR 参与肠易激综合征大鼠的中枢敏化。

Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome.

机构信息

Fujian Provincial Key Laboratory of Neuroglia and Diseases Laboratory of Pain Research Department of Physiology and Pathophysiology Fujian Medical University Fuzhou Fujian China.

2013 Seven-year Clinical Medicine Fujian Medical University Fuzhou Fujian China.

出版信息

Brain Behav. 2017 Feb 22;7(3):e00650. doi: 10.1002/brb3.650. eCollection 2017 Mar.

Abstract

OBJECTIVE

The roles of hippocampal AMPARs were investigated in irritable bowel syndrome (IBS)-like rats to clarify the central sensitization mechanisms.

METHODS

IBS model was induced by neonatal maternal separation. The effects of AMPARs on visceral hypersensitivity were examined by the responses of abdominal muscle to colorectal distension after the bilateral intrahippocampal injections of CNQX (an AMPAR inhibitor). The expressions of hippocampal AMPARs (GluR1 and GluR2) were determined by Western blot.

RESULTS

The IBS-like rats showed visceral hypersensitivity when compared with controls. Bilateral intrahippocampal injections of CNQX alleviated the visceral pain in IBS-like rats. The maximal effect appeared at the time point of 30 min, and the duration lasted for 90 min after CNQX application, under 40 and 60 mmHg CRD. The expressions of hippocampal GluR2 significantly increased in IBS-like rats when compared with controls (<.05). However, the levels of hippocampal GluR1 had no significant differences in rats. Hippocampal LTP induced by HFS was significantly enhanced when compared with controls (<.05). The expressions of GluR2 significantly increased in the control and IBS-like rats after 60 min LTP of recordings (<.05), but not GluR1.

CONCLUSION

Neonatal maternal separation enhances the expression of GluR2 and facilitates the LTP in the hippocampus, which could lead to the formation of visceral hypersensitivity when grown up.

摘要

目的

研究海马 AMPAR 在肠易激综合征(IBS)样大鼠中的作用,以阐明中枢敏化机制。

方法

通过新生期母体分离诱导 IBS 模型。通过双侧海马内注射 CNQX(AMPA 受体抑制剂)后对结肠直肠扩张的腹肌反应,观察 AMPAR 对内脏高敏的影响。通过 Western blot 测定海马 AMPAR(GluR1 和 GluR2)的表达。

结果

与对照组相比,IBS 样大鼠表现出内脏高敏性。双侧海马内注射 CNQX 减轻了 IBS 样大鼠的内脏疼痛。在 40 和 60mmHg CRD 下,CNQX 应用后 30min 出现最大效应,持续 90min。与对照组相比,IBS 样大鼠海马 GluR2 的表达显著增加(<0.05)。然而,对照组和 IBS 样大鼠的海马 GluR1 水平无显著差异。与对照组相比,HFS 诱导的海马 LTP 明显增强(<0.05)。与对照组和 IBS 样大鼠相比,记录 60minLTP 后 GluR2 的表达显著增加(<0.05),但 GluR1 没有增加。

结论

新生期母体分离增强了 GluR2 的表达,并促进了海马体的 LTP,这可能导致长大后内脏高敏性的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83a8/5346530/d77620a29fc4/BRB3-7-e00650-g001.jpg

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