Inhibition of p38 MAPK regulates epileptic severity by decreasing expression levels of A1R and ENT1.

Inhibition of p38 MAPK regulates epileptic severity by decreasing expression levels of A1R and ENT1.
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抑制 p38 MAPK 通过降低 A1R 和 ENT1 的表达水平来调节癫痫严重程度

DOI:
10.3892/mmr.2020.11614
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发表时间:
2020-12
影响因子:
3.4
通讯作者:
Xu Z
Xu Z
中科院分区:
医学4区
文献类型:
--
作者:
Zhou X;Chen Q;Huang H;Zhang J;Wang J;Chen Y;Peng Y;Zhang H;Zeng J;Feng Z;Xu Z

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癫痫是一种慢性神经系统疾病。体内兴奋性神经递质谷氨酸的过度增加导致神经递质失衡和神经元过度兴奋,导致癫痫发作。长期反复发作会导致行为和认知改变,甚至使死亡风险增加2- 3倍。腺苷A1受体(A1 R)是腺苷系统的一员,具有显著的抗惊厥作用,腺苷水平受1型平衡型核苷转运蛋白(ENT 1)的调控,此外,p38 MAPK信号通路也参与ENT 1的调控,但其抑制剂对A1 R和ENT 1表达水平的影响尚不清楚。因此,本研究采用SB 203580抑制大鼠p38 MAPK信号通路,检测急性氯化锂-匹罗卡品致痫大鼠脑组织A1 R和ENT 1的表达水平。SB 203580可减轻大鼠海马神经元病理损伤,延长癫痫发作潜伏期,减少癫痫发作次数,降低A1 R和ENT 1蛋白水平。
Epilepsy is a chronic nervous system disease. Excessive increase of the excitatory neurotransmitter glutamate in the body results in an imbalance of neurotransmitters and excessive excitation of neurons, leading to epileptic seizures. Long-term recurrent seizures lead to behavior and cognitive changes, and even increase the risk of death by 2- to 3-fold relative to the general population. Adenosine A1 receptor (A1R), a member of the adenosine system, has notable anticonvulsant effects, and adenosine levels are controlled by the type 1 equilibrative nucleoside transporter (ENT1); in addition the p38 MAPK signaling pathway is involved in the regulation of ENT1, although the effect of its inhibitors on the expression levels of A1R and ENT1 is unclear. Therefore, in the present study, SB203580 was used to inhibit the p38 MAPK signaling pathway in rats, and the expression levels of A1R and ENT1 in the brain tissue of rats with acute LiCl-pilocarpine-induced status epilepticus was detected. SB203580 decreased pathological damage of hippocampal neurons, prolonged seizure latency, reduced the frequency of seizures, and decreased levels of A1R and ENT1 protein in rats.
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