中药复方熄风胶囊对氯化锂-匹罗卡品致痫大鼠海马电压门控性Ⅰ型钠通道α亚基蛋白表达的影响

Effects of Xifeng Capsule on the expression of voltage-gated type I sodium channel α subunit protein (Nav1.1) in hippocampus of epileptic rats induced by lithium chloride and pilocarpine

关键词:  电压门控性Ⅰ型钠通道α亚基蛋白  熄风胶囊  癫痫  匹罗卡品

Key words:  voltage-gated sodium channel α subunit protein  Xifeng Capsule  epilepsy  pilocarpine

摘要:

[目的]研究中药复方熄风胶囊对氯化锂-匹罗卡品致痫大鼠海马电压门控性Ⅰ型钠通道α亚基蛋白（Nav1.1）表达的影响。[方法]建立氯化锂-匹罗卡品致痫大鼠模型。实验大鼠随机分为5组：空白组、模型组、熄风胶囊低剂量治疗组（熄低组）、熄风胶囊中剂量治疗组（熄中组）、熄风胶囊高剂量治疗组（熄高组）。分别通过免疫组织化学染色法检测实验大鼠海马Nav1.1的表达。[结果]Nav1.1蛋白在IE大鼠海马的表达，发现致痫大鼠海马CA1区和DG区神经元结构基本正常，且Nav1.1变化不明显，在CA3区，模型组致痫大鼠神经元变性、坏死明显，Nav1.1在神经元变性、坏死部位染色变浅，甚至消失，在变性、坏死神经元周围的正常组织中染色增强。其中，模型组可见CA3区神经元退变、坏死，Nav1.1在神经元退变、坏死部位染色变浅，甚至消失，而在熄风胶囊治疗组中，随剂量增大，退变、消失的神经元减少，同时棕褐色区域减少程度减低，均与剂量成正相关，但在变性、坏死的神经元周围的正常组织中染色增强不明显，而且从定量分析来看，模型组Nav1.1的表达量增多，而各熄风胶囊治疗组却增加不明显。[结论]熄风胶囊可能通过保护海马神经元，调节IE大鼠海马神经元Nav1.1的表达，推测其可通过对钠通道的抑制作用以降低神经元细胞膜兴奋性而发挥抗癫痫作用。

Abstract:

[Objective] To study the effect of Xifeng Capsule on the expression of voltage-gated type I sodium channel α subunit protein (Nav1.1) in hippocampus of epileptic rats induced by lithium chloride and pilocarpine.[Methods] Established the epileptic rat model was induced by lithium chloride and pilocarpine. The experimental rats were randomly divided into 5 groups:normal control group (blank group),model control group (model group),low dose group of Xifeng Capsule (low dose group),medium dose group of Xifeng Capsule (medium dose group),and high dose group of Xifeng Capsule (high dose group). The expressions of Nav1.1 in hippocampus of experimental rats were detected by immunohistochemical staining.[Results] Through the expression of Nav1.1,we found the neuronal structure of CA1 and DG regions of epileptic rats were basically normal,and the changes of Nav1.1 were not obvious. In the CA3 area,the neurons in the model group were denatured and necrosis,in which,the staining of Nav1.1 became shallower or even disappeared,and increased in the normal tissues around the denatured and necrotic neurons. In the model group,the degeneration of neurons in the CA3 area was observed,and the staining of Nav1.1 in necrotic site became shallower or even disappeared;while in the treatment group of Xifeng Capsule,the number of degeneration and disappearance of neurons was decreased with the increase of the dose of Xifeng Capsule. At the same time,the reduction in the degree of brown area lessen was positively correlated with the dosage. However,the staining intensity was not obvious in the normal tissues around the denatured and necrotic neurons. Furthermore,from quantitative analysis,the expressions of Nav1.1 number in the model group were increased,while the number did not increase significantly in each Xifeng Capsule treatment group.[Conclusion] Xifeng Capsule may protect hippocampal neurons and regulate the expression of Nav1.1 in hippocampal neurons of IE rats. It is speculated that Xifeng Capsule can play an antiepileptic effect by inhibiting sodium channel and reducing the excitability of neuronal cell membrane.