【作者】 李海峰；

【导师】 夏哲智；

【作者基本信息】 浙江大学 ， 儿科学， 2008， 硕士

【摘要】 研究背景癫痫是小儿神经系统的常见病患之一,治疗癫痫的最主要的方法是长期应用抗癫痫药物(Anti-Epilepsy Drugs,AEDs),患者服药的依从性是决定抗癫痫治疗成败的重要因素。而抗癫痫药物的副作用常对患儿服药的依从性产生影响。丙戊酸钠和托吡酯是目前临床应用最广泛的抗癫痫药物,较多文献报道丙戊酸钠引起肥胖,托吡酯引起消瘦、生长迟缓,但有关体质量变化的发生机制国内外仍存在争议,尤其在儿童方面报导较少。目的本研究旨在通过较为全面的监测BMI、血清瘦素、脂联素、瘦素/脂联素、胰岛素及胰岛素抵抗指数等代谢相关指标,进一步探索丙戊酸钠、托吡酯对癫痫儿童体重和糖脂代谢的影响机制,以达到及时发现和处理药物的副反应,提高患儿服药的依从性和治疗的成功率。方法研究对象定为2007年本院初诊的癫痫患儿,根据2001年国际抗癫痫联盟(ILAE)制定的癫痫发作分类标准,分成丙戊酸钠组、托吡酯组,收集治疗前后的各代谢相关指标(BMI、血清瘦素、脂联素、瘦素/脂联素、血脂全套、空腹血糖、胰岛素、胰岛素抵抗指数),最后对所有数据进行统计分析。结果1.丙戊酸钠组瘦素/脂联素值在治疗后有增加,并有显著性差异(t=2.052,p=0.040),瘦素值治疗后有增加,但无显著性差异(t=0.724,p=0.469),脂联素治疗后有降低,亦无显著性差异(t=1.610,p=0.107),BMI值的改变无显著性差异(t=0.675,p=0.500);托吡酯组治疗后BMI、瘦素/脂联素值降低而脂联素水平增加,并均有显著性差异(p＜0.05),瘦素值治疗后的改变无显著性差异(t=0.065,p=0.948)。2.丙戊酸钠组中瘦素/脂联素变化值与瘦素、胰岛素及HOMA指数变化值之间呈正相关(p＜0.05),托吡酯组中瘦素/脂联素变化值与脂联素变化值呈负相关(p＜0.05)。3.代谢指标(BMI、瘦素、脂联素、瘦素/脂联素及HOMA指数)的变化值与托吡酯、丙戊酸钠的药物剂量之间无统计学相关性。结论1.丙戊酸钠能显著提高癫痫患儿血清瘦素/脂联素水平,而对血清瘦素、脂联素及BMI改变不明显;托吡酯能显著降低BMI及瘦素/脂联素水平,并提高脂联素,但对血清瘦素水平改变不明显。通过对瘦素/脂联素的监测,将有助于及时发现丙戊酸钠、托吡酯对体重和代谢方面的副反应。2.托吡酯、丙戊酸钠的药物剂量与各个代谢指标(BMI、血清瘦素、脂联素、瘦素/脂联素及HOMA指数)的变化值之间无统计学相关性。3.丙戊酸钠组和托吡酯组治疗前后的血清胰岛素及HOMA指数变化均无显著性差异。更多还原

【Abstract】 Background: Epilepsy is one of the pediatric nervous system diseases, and the major treatment is the long term application of Anti-Epilepsy Drugs (AEDs). The compliableness of patients is an important factor to determine the curative effect, but the side effects of AEDs may affect the compliableness. sodium valproate and topiramate are the two AEDs which are widely applied nowadays. Some literature reported that Sodium valproate arouses obesity and topiramate arouses emaciation and growth retardation. But the mechanism of the change of BMI is still disputed in or outside the nation, especially in children.Objective: To explore the mechanism of BMI and metabolism changes insodium valproate and topiramate treatment on children with epilepsy by monitoring the metabolism indexes such as BMI, leptin, adiponectin, L/A(leptin/ adiponectin), insulin and HOMA index, et al. The purpose of the study is to improve the timeliness for early detection and treatment on side effects and to improve the compliableness and curative effect. Methods: Children with epilepsy were included in their first visitto the doctor in 2007. According to criterion of ILAE (2001), the objects were divided to sodium valproate group, topiramate group. The related metabolism indexes such as BMI, leptin, adiponectin, L/A (leptin/ adiponectin), lipid, fasting blood glucose, insulin and HOMA index, et al before and after treatment were collected. Data were analyzed and compared by SPSS12.0.Results: There was a significant increase on the index of L/A in sodiumvalproate group after the treatment(t=2.052, p=0.040); but there was no significant difference on leptin although it increased after the treatment (t=0.724,p=0.469); and there was no significant difference on adiponectin although it decreased after the treatment (t=1.610, p=0.107); there was no significant difference on BMI after the treatment(t=0.675, p=0.500). There was a significant decrease on BMI and L/A and an increase on adiponectin in topiramate group(p<0.05). There was no significant difference on leptin in topiramate group(t=0.065, p=0.948). Before and after the treatment, the change value of L/A positively related to change value of leptin, insulin and HOMA index in sodium valproate group(p<0.05), and the change value of L/A negatively related to the change value of adiponectin in topiramate group(p<0.05). There was no relationship between the change value of metabolism indexes and the dosage of sodium valproate or topiramate (p>0.05).Conclusions: Sodium valproate could increase the level of L/A inchildren with epilepsy, but the effect on leptin, adiponectin and BMI was not significant; topiramate could decrease BMI index and L/A while increase the level of adiponectin, but the effect on leptin was not significant. Monitoring the L/A index could improve the timeliness for early detecting the side effect on BMI and metabolism in sodium valproate or topiramate treatment. The dosage of AEDs could not be a sensitive index for monitoring the side effect. There were no difference for the changes of insulin and HOMA index in both sodium valproate and topiramate group.更多还原