丙戊酸钠对成、幼年大鼠血脂、血清瘦素及大脑皮质的影响

Effects of valproate acid on blood lipid, serum leptin and cerebral cortex in juvenile and adult rat

摘要:

目的：研究并比较丙戊酸钠（VPA）对成、幼年大鼠血脂、血清瘦素及大脑皮质的影响。方法健康幼年雌性Sprague-Dawley (SD)大鼠（生后21 d）及成年雌性SD大鼠（生后2月）随机分为幼年对照组、幼年VPA、成年对照组、成年VPA组4组，每组10只，对照组每日直接灌胃生理盐水1～2 mL，VPA组直接灌胃给药每日VPA 200 mg/kg，干预6周后处死，取血清标本及大脑皮质标本，检测血脂(总胆固醇、甘油三酯、低密度脂蛋白)、放射免疫分析法检测血清瘦素；大脑皮质做尼氏染色及髓鞘染色以评估脑损伤。结果成年、幼年VPA组体重、空腹血脂及瘦素水平均高于各自的对照组，差异均有统计学意义 (P<0.05)。与成年VPA组比较，幼年VPA组大鼠血清LEP、血脂增值水平更高（P<0.05）。脑皮质髓鞘染色VPA组平均纤维密度较其对照组明显下降，差异有统计学意义(P<0.05)；尼氏染色VPA组甲苯胺蓝染色神经元数目较其对照组略减少，差异无统计学意义(P>0.05)。结论 VPA可显著增高成、幼年大鼠的血清瘦素及血脂水平，尤其见于幼年鼠。长期应用VPA对幼年大鼠大脑皮质髓鞘有一定影响，对神经元影响不显著。［中国当代儿科杂志，2010，12（6）：479-482］

Abstract:

OBJECTIVE: To study the effects of valproate acid (VPA) on serum lipid and leptin levels and cerebral cortex in juvenile and adult rats. METHODS: Twenty healthy juvenile female Sprague-Dawley (SD) rats (21-day-old) and twenty healthy adult female SD rats (2-month-old) were randomly divided into four groups (n=10 each): juvenile control, juvenile VPA, adult control and adult VPA. Juvenile and adult VPA groups were fed with VPA 200 mg/kg daily, while the two control groups were fed with normal saline. The body weights were recorded weekly. Six weeks after feeding, serum and brain samples were obtained. Serum lipid levels including total cholesterol (TC), triglycerides (TG) and lower density lipoprotein cholesterol (LDL-C) were determined. Serum leptin (LEP) levels were measured by radioimmunoassay (RIA). Myelin staining and Nissl staining were used to evaluate the changes of brain tissues. RESULTS: The weight and serum LEP and lipid levels in both juvenile and adult VPA groups increased significantly compared with those in the control groups (P<0.05). The juvenile VPA group had more increased serum LEP and lipid levels than the adult VPA group (P<0.05). The Myelin staining showed that the average fiber density in the VPA groups was significantly lower than that in the control groups (P<0.05). The Nissl staining showed that the number of toluidine blue staining neurons in the VPA groups was not statistically different from the control groups. CONCLUSIONS: VPA may increase serum LEP and lipid levels in both juvenile and adult rats, and more increased levels may be found in juvenile rats. Longterm VPA treatment may have an adverse effect on brain myelination, but no effect on neurons.［Chin J Contemp Pediatr, 2010, 12 (6):479-482］