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P2X7受体拮抗剂可使实验性溃疡性结肠炎后的回肠肌间神经元恢复。

P2X7 receptor antagonist recovers ileum myenteric neurons after experimental ulcerative colitis.

作者信息

Souza Roberta Figueiroa, Evangelinellis Mariá Munhoz, Mendes Cristina Eusébio, Righetti Marta, Lourenço Múcio Cevulla Silva, Castelucci Patricia

机构信息

Department of Anatomy, University of São Paulo, São Paulo 05508-900, Brazil.

Department of Surgery, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-900, Brazil.

出版信息

World J Gastrointest Pathophysiol. 2020 Jun 20;11(4):84-103. doi: 10.4291/wjgp.v11.i4.84.

Abstract

BACKGROUND

The P2X7 receptor is expressed by enteric neurons and enteric glial cells. Studies have demonstrated that administration of a P2X7 receptor antagonist, brilliant blue G (BBG), prevents neuronal loss.

AIM

To report the effects of BBG in ileum enteric neurons immunoreactive (ir) following experimental ulcerative colitis in .

METHODS

2,4,6-trinitrobenzene sulfonic acid (TNBS group, = 5) was injected into the distal colon. BBG (50 mg/kg, BBG group, = 5) or vehicle (sham group, = 5) was given subcutaneously 1 h after TNBS. The animals were euthanized after 24 h, and the ileum was removed. Immunohistochemistry was performed on the myenteric plexus to evaluate immunoreactivity for P2X7 receptor, neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), HuC/D and glial fibrillary acidic protein.

RESULTS

The numbers of nNOS-, ChAT-, HuC/D-ir neurons and glial fibrillary acidic protein-ir glial cells were decreased in the TNBS group and recovered in the BBG group. The neuronal profile area (μm) demonstrated that nNOS-ir neurons decreased in the TNBS group and recovered in the BBG group. There were no differences in the profile areas of ChAT- and HuC/D-ir neurons.

CONCLUSION

Our data conclude that ileum myenteric neurons and glial cells were affected by ulcerative colitis and that treatment with BBG had a neuroprotective effect. Thus, these results demonstrate that the P2X7 receptor may be an important target in therapeutic strategies.

摘要

背景

P2X7受体由肠神经元和肠胶质细胞表达。研究表明,给予P2X7受体拮抗剂亮蓝G(BBG)可预防神经元丢失。

目的

报告BBG对实验性溃疡性结肠炎后回肠肠神经元免疫反应性(ir)的影响。

方法

将2,4,6-三硝基苯磺酸(TNBS组,n = 5)注入结肠远端。TNBS注射1小时后皮下给予BBG(50mg/kg,BBG组,n = 5)或溶剂(假手术组,n = 5)。24小时后对动物实施安乐死并取出回肠。对肌间神经丛进行免疫组织化学,以评估P2X7受体、神经元型一氧化氮合酶(nNOS)、胆碱乙酰转移酶(ChAT)、HuC/D和胶质纤维酸性蛋白的免疫反应性。

结果

TNBS组中nNOS、ChAT、HuC/D免疫反应性神经元以及胶质纤维酸性蛋白免疫反应性胶质细胞数量减少,而BBG组中恢复。神经元轮廓面积(μm)显示,TNBS组中nNOS免疫反应性神经元减少,BBG组中恢复。ChAT和HuC/D免疫反应性神经元的轮廓面积无差异。

结论

我们的数据表明,回肠肌间神经丛神经元和胶质细胞受到溃疡性结肠炎的影响,而BBG治疗具有神经保护作用。因此,这些结果表明P2X7受体可能是治疗策略中的一个重要靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc98/7303980/b9b2ce5d596e/WJGP-11-84-g001.jpg

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