高压氧与丙戊酸钠对外伤性癫疒间模型的治疗作用及机制研究

Comparison study of therapeutic effect and its mechanism of hyperbaric oxygen and valproic acid on post-traumatic animal epilepsy models

目的对比丙戊酸钠与高压氧对外伤性癫疒间的治疗作用,并探究其治疗机制。方法 60只成年SD大鼠随机分为4组:对照组(n=12)、模型组(n=12)、丙戊酸钠组(n=18)和高压氧组(n=18),采用皮质注射氯化亚铁制作外伤性癫疒间动物模型。制模成功后,丙戊酸钠组予鼻饲丙戊酸钠,高压氧组予高压氧治疗,观察大鼠行为学及脑电图表现,应用RT-PCR检测c-fos及c-jun m RNA的表达水平。结果高压氧组癫疒间发作较模型组及丙戊酸钠组明显减少,疒间样放电频率减慢和波幅降低。丙戊酸钠组c-fos m RNA的表达水平较模型组显著升高(P<0.01),高压氧组c-fos m RNA的表达水平较丙戊酸钠组明显下降(P<0.05)。高压氧组c-jun m RNA的表达水平较模型组及丙戊酸钠组均明显下降(P<0.05)。结论高压氧通过降低颅脑损伤后脑皮质的高兴奋性及抑制JNK信号通路的激活,达到抗癫疒间效果。丙戊酸钠无法通过上述机制发挥作用而效果欠佳。

Objective To compare the therapeutic effect ofvalproic acid （VPA） and hyperbaric oxygen therapy （HBO） on post-traumatic epilepsy （PTE） and investigate their therapeutic mechanisms. Methods Sixty adult SD rats were randomly divided into 4 groups： control group （n = 12）, model group （n = 12）, VPA group （n = 18） and HBO group （n = 18）. The PTE animal models were established by injecting ferrous chloride. The VPA group was treated with VPA solution. The HOB group was treated by HBOT. The behavior and EEG changes after epilepsy attack of rats were observed and recorded in all the groups. The expressions of c-fos and c-jun mRNA were detected by RT-PCR. Results Compared with the model group and VPA group, the frequency of post-traumatic seizure attacks was obviously reduced in HBO group. And elongation of latent period of epileptiform discharge, fi＇equency reduction, amplitude decrease were also observed in EEG. Compared to the model group, the expression level of c-fos mRNA increased obviously in VPA group （P 〈 0.01）. Compared to the VPA group, the expression level ofc-fos mRNA decreased significantly in the HBO group （P〈 0.05）. Compared to the model group and VPA group, the expression level ofc-jun mRNA decreased significantly in the HBO group （P〈 0.05）. Conclusions Hyperbaric oxygen may inhibit the cortical excitability and the activation of JNK signal pathway, thus exerting an antiepileptic effect. VPA could not play a role by the above mechanism, thereby being less effective than hyperbaric oxygen.