丙戊酸钠对中性粒细胞氧化代谢与机体氧化应激的影响

Effects of sodium valproate on neutrophils＇ oxidative metabolism and oxidant status in children with idiopathic epilepsy

目的探讨长期丙戊酸钠（VPA）1：3服抗癫痫治疗对癫痫患儿中性粒细胞氧化代谢及机体氧化应激的影响。方法选择健康体检儿童30名与癫痫患儿26例。观察对照组与癫痫组患儿用药前、VPA治疗6个月、12个月后中性粒细胞活化率、刺激指数和血浆中性粒细胞髓过氧化物酶（MPO）活性，并检测血浆抗氧化酶系统超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH—Px）活性以及脂质过氧化代谢产物丙二醛（MDA）含量等氧化应激指标的变化。结果VPA治疗后6个月与12个月患儿中性粒细胞活化率分别为（11．50±6．52）％与（14．31±5．76）％，均高于对照组（5．90±3．77）％与癫痫尚未服药时（7．42±3．15）％（P〈0．01）；刺激指数VPA治疗6个月（474．88±118．98）、治疗12个月（416．31±110．00）均低于对照组（544．83±140．83）与癫痫尚未服药时（535．23±111．55）（P〈0．05）；VPA治疗后血浆MPO活性、MDA含量均较正常对照组与癫痫尚未服药时高（P〈0．05或0．01）；SOD、CAT活性均较对照组与尚未服药时低（P〈0．05或0．01）；GSH．Px活性在各阶段患儿间差异无统计学意义。多元逐步回归分析显示服药疗程、中性粒细胞活化率与血浆MDA含量呈正相关（P〈0．05），血浆SOD活性与MDA含量呈负相关（P〈0．05）。结论VPA治疗致患儿中性粒细胞的活化与机体氧化应激之间具有相关性，而且治疗疗程可能是影响癫＇痫患儿氧化应激损伤的关键因素之一。

Objective To evaluate the influence of VPA treatment on neutrophils＇ oxidative metabolism and oxidant status in epileptic children. Method Twenty-six newly diagnosed epileptic children with idiopathic epilepsy and 30 healthy children were included in the study. The activation rates of neutrophils and stimulation indexes were detected in patients before and 6 months and 12 months after VPA treatment respectively and in all the healthy children by flow cytometry with dihydrorhodamine as fluorochrome. The activities of myeloperoxidase from neutrophils were also detected. Malondialdehyde as an indicator of lipid peroxidation and antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase were measured in plasma respectively. Result The activation rates of neutrophils in patients treated with VPA after 6 and 12 months were （11.50 ± 6.52）% and （14.31 ± 5.76）% respectively, which were significantly higher than the data of control group （5.90 ±3.77 ）% and pretreatment level （7.42 ± 3.15）%. The stimulation indexes 6 and 12 months after VPA therapy were （474. 88 ± 118. 98） and （416. 31 ± 110. 00） respectively, which were lower than the data of control group （544. 83 ± 140. 83 ） and pretreatment level （ 535.23 ± 111.55 ）. The plasma MPO activities and levels of maJondialdehyde in VPA treated patients were also higher while the activities of SOD and CAT were significantly lower than the control and untreated groups. GSH-Px levels did not differ between the groups. Multiple linear regression analysis showed that the time of treatment and the activation rates of neutrophils were indicators which had positive correlation with the levels of plasma MDA and that SOD activities wereinversely correlated with MDA levels. Conclusion VPA which is frequently used in childhood epilepsy may activate the neutrophils of patients and cause oxidative stress and prolonged treatment may aggravate it.