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P2X2在糖尿病大鼠视网膜中可能的神经保护作用。

Possible neuroprotective role of P2X2 in the retina of diabetic rats.

作者信息

Mancini Jorge E, Ortiz Gustavo, Potilinstki Constanza, Salica Juan P, Lopez Emiliano S, Croxatto J Oscar, Gallo Juan E

机构信息

1Department of Ophthalmology, Nanomedicine & Vision Group, Facultad de Ciencias Biomédicas, Universidad Austral, Av. Juan D. Perón 1500, B1629AHJ Pilar, Buenos Aires Argentina.

3Instituto de Investigaciones en Medicina Traslacional (IIMT), Universidad Austral, Consejo Nacional de Investigaciones Científicas y Técnicas (UA-CONICET), Pilar, Buenos Aires, Argentina.

出版信息

Diabetol Metab Syndr. 2018 Apr 12;10:31. doi: 10.1186/s13098-018-0332-7. eCollection 2018.

Abstract

BACKGROUND

Purinergic receptors are expressed in different tissues including the retina. These receptors are involved in processes like cell growth, proliferation, activation and survival. ATP is the major activator of P2 receptors. In diabetes, there is a constant ATP production and this rise of ATP leads to a persistent activation of purinergic receptors. Antagonists of these receptors are used to evaluate their inhibition effects. Recently, the P2X2 has been reported to have a neuroprotective role.

METHODS

We carried out a study in groups of diabetic and non-diabetic rats (N = 5) treated with intraperitoneal injections of PPADS, at 9 and 24 weeks of diabetes. Control group received only the buffer. Animals were euthanized at 34 weeks of diabetes or at a matching age. Rat retinas were analyzed with immunohistochemistry and western blot using antibodies against GFAP, P2X2, P2Y2 and VEGF-A.

RESULTS

Diabetic animals treated with PPADS disclosed a much more extended staining of VEGF-A than diabetics without treatment. A lower protein expression of VEGF-A was found at the retina of diabetic animals without treatment of purinergic antagonists compared to diabetics with the antagonist treatment. Inhibition of P2X2 receptor by PPADS decreases cell death in the diabetic rat retina.

CONCLUSION

Results might be useful for better understanding the pathophysiology of diabetic retinopathy.

摘要

背景

嘌呤能受体在包括视网膜在内的不同组织中表达。这些受体参与细胞生长、增殖、激活和存活等过程。ATP是P2受体的主要激活剂。在糖尿病中,ATP持续产生,这种ATP的增加导致嘌呤能受体的持续激活。这些受体的拮抗剂被用于评估其抑制作用。最近,据报道P2X2具有神经保护作用。

方法

我们对糖尿病大鼠和非糖尿病大鼠(每组N = 5)进行了一项研究,在糖尿病9周和24周时腹腔注射PPADS。对照组仅接受缓冲液。在糖尿病34周或匹配年龄时对动物实施安乐死。使用针对GFAP、P2X2、P2Y2和VEGF - A的抗体,通过免疫组织化学和蛋白质印迹法对大鼠视网膜进行分析。

结果

用PPADS治疗的糖尿病动物的VEGF - A染色比未治疗的糖尿病动物更广泛。与接受拮抗剂治疗的糖尿病动物相比,未用嘌呤能拮抗剂治疗的糖尿病动物视网膜中VEGF - A的蛋白表达较低。PPADS对P2X2受体的抑制可减少糖尿病大鼠视网膜中的细胞死亡。

结论

这些结果可能有助于更好地理解糖尿病视网膜病变的病理生理学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f7d/5898034/7605d4a38c2b/13098_2018_332_Fig1_HTML.jpg

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