α-硫辛酸对电点燃致痫大鼠行为学及海马p38MAPK表达的影响

The effect of α-lipoic acid on the expression of p38MAPK in Hippocampus and behavior of amygdala electrical kindling seizures in rats

目的探讨α-硫辛酸(α-LA)对电点燃致痫大鼠行为及海马p38MAPK表达的影响。方法将雄性Wistar大鼠随机分为正常对照组、α-LA组、假手术组、ES组、电低α-LA组、电高α-LA组。检测点燃前、后发放阈值(ADT)及达到每个发作等级所需的累积刺激数和累积后发放持续时间(ADD),应用Western blot检测海马p38MAPK及p-p38MAPK表达水平,碘化丙啶(PI)染色检测海马神经元凋亡率。结果与ES组相比:电高α-LA组达到第一次Ⅴ级发作所需的累积电刺激数明显增多(P<0.05)、点燃后ADT明显增高(P<0.05);电低α-LA组和电高α-LA组海马p-p38MAPK表达水平和神经元凋亡率明显降低(P<0.05)、达到第一次Ⅴ级发作所需的累积ADD明显缩短(P<0.05)。各组点燃后ADT较点燃前均明显降低(P<0.05)。结论癫痫可导致海马组织中pp38MAPK表达上调、神经元凋亡率明显增加;α-LA能够有效降低癫痫发作等级、缩短ADD、下调p-p38MAPK表达水平并降低神经元凋亡率,从而推测α-LA可通过抗凋亡途径来发挥神经保护作用。

Objective To explore the effects of α-LA on the behavior and the expression of p38MAPK in hippocam- pus of amygdala electrical kindling rats. Methods Male Wistar rats were randomly distributed to six groups, normal control group,α-LA group, sham-operation group, ES group, low dose of α-LA group, high dose of α-LA group. Pre-kindling and post-kindling ADT were determined, the numbers of cumulative stimulations and ADD of respective seizure stage were recor- ded. Subsequently,the expressions of the p38MAPK and p-p38MAPK protein in hippoeampus were tested by Western blot and apoptosis rate of hippocampal neuron was detected by PI dyeing. Results The number of cumulative stimulations to reach the first seizure stage 5 and post-kindling ADT in high dose of α-LA group was increased obviously compared to ES group （P 〈 0.05 ）. The expression of p-p38MAPK protein in hippoeampus and the apoptosis rate of hippocampal neuron and the numbers of cumulative ADD to reach the first seizure stage 5 of both low dose of α-LA group and high dose of α-LA group were decreased obviously compared to ES group （P 〈 0.05 ）. Post-kindling ADT was decreased obviously compared to pre-kindling ADT of each group. Conclusion The expressions of p-p38MAPK protein and the apoptosis of hippocampal neuron were increased after epilepsy. While the phenomena shown above were reversed after administering ^-lipoic acid. Thus, we can speculate that α-lipoic acid may play a neuroproteetive role in epilepsy by inhibiting apoptosis.