一种硫化氢供体通过蛋白激酶 C 信号通路抑制大鼠戊四氮诱导的癫痫发作。
A hydrogen sulfide donor suppresses pentylenetetrazol-induced seizures in rats via PKC signaling.
机构信息
Dept. of Physiology, Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China; Dept. of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Dept. of Physiology, Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
出版信息
Eur J Pharmacol. 2021 May 5;898:173959. doi: 10.1016/j.ejphar.2021.173959. Epub 2021 Feb 19.
Epilepsy is a serious neurological disorder. Available antiepileptic drugs are still lacking. Hydrogen sulfide (HS), a neuron-protective endogenous gasotransmitter, is reported to have effect on epilepsy. But it remains to be determined for its mechanism. In the present study, we found that a novel carbazole-based HS donor could effectively suppress pentylenetetrazol-induced seizures in rats. The HS donor could alleviate not only the epileptic behavior of animals but also the hippocampal EEG activity of seizures. The HS donor down-regulated the expression of aquaporin 4 in the hippocampus of epilepsy rats. The HS donor also decreased the seizure-induced release of inflammatory cytokines including IL-1β, IL-6 and TNF-α. In addition, the HS donor increased protein kinase C (PKC) expression in the hippocampus of epilepsy rats. These effects of the HS donor on epilepsy rats were attenuated after blockade of PKC signaling by Go6983, suggesting that PKC signaling participated in the antiepileptic process of HS donor. Taken together, the HS donor has a beneficial effect on epilepsy control in a PKC-dependent manner.
癫痫是一种严重的神经障碍。现有的抗癫痫药物仍然缺乏。硫化氢（HS）是一种具有神经元保护作用的内源性气体递质，据报道对癫痫有作用。但其机制仍有待确定。在本研究中，我们发现一种新型咔唑基 HS 供体可有效抑制戊四氮诱导的大鼠癫痫发作。HS 供体不仅能减轻动物的癫痫行为，还能减轻癫痫发作时的海马 EEG 活动。HS 供体下调癫痫大鼠海马中水通道蛋白 4 的表达。HS 供体还减少了癫痫发作引起的炎症细胞因子（包括白细胞介素 1β、白细胞介素 6 和肿瘤坏死因子-α）的释放。此外，HS 供体增加了癫痫大鼠海马中的蛋白激酶 C（PKC）表达。用 Go6983 阻断 PKC 信号后，HS 供体对癫痫大鼠的这些作用减弱，表明 PKC 信号参与了 HS 供体的抗癫痫过程。综上所述，HS 供体以 PKC 依赖的方式对癫痫控制有有益的影响。
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