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使用典型和非典型抗精神病药物治疗的不同类型精神分裂症中的抗氧化酶与脂质过氧化作用

Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics.

作者信息

Zhang Xiang Yang, Tan Yun Long, Cao Lian Yuan, Wu Gui Ying, Xu Qi, Shen Yan, Zhou Dong Feng

机构信息

Institute of Mental Health, Peking University, Beijing, PR China.

出版信息

Schizophr Res. 2006 Jan 31;81(2-3):291-300. doi: 10.1016/j.schres.2005.10.011. Epub 2005 Nov 23.

Abstract

There is accumulating evidence of altered antioxidant enzyme activities and increased levels of lipid peroxidation in schizophrenia. Free radical-mediated abnormalities may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. However, few studies have evaluated both antioxidant enzymes and lipid peroxidation in the same schizophrenic patient groups treated with typical or atypical antipsychotics. Plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 92 medicated schizophrenia including paranoid (n=34), disorganized (n=18) and residual subtypes (n=40), as well as in control subjects (n=50). The results showed that activities of SOD and GSH-Px were decreased but levels of MDA were elevated in patients with a chronic form of schizophrenia as compared with normal controls. SOD and GSH-Px activities were found to be significantly lower in paranoid and residual subtypes compared to both disorganized subtype and the control group. MDA levels were significantly higher in all subtypes compared to the control group. There were no significant differences in any parameters measured among all three subgroups treated with clozapine (n=44), risperidone (n=20) and typical antipsychotics (n=28). Additionally, a significantly higher MDA levels, but a significantly lower CAT activity was noted in female than male patients. These results suggest that oxidative stress may be implicated in the pathophysiology of all subtypes of schizophrenia, which may contribute to the increased membrane lipid peroxidation. Long-term treatments with typical and atypical antipsychotics may produce the similar effects on the antioxidant enzymes and lipid peroxidation.

摘要

越来越多的证据表明,精神分裂症患者体内抗氧化酶活性发生改变,脂质过氧化水平升高。自由基介导的异常可能导致精神分裂症症状的特定方面及其治疗并发症。然而,很少有研究在接受传统或非典型抗精神病药物治疗的同一精神分裂症患者群体中同时评估抗氧化酶和脂质过氧化情况。采用既定方法分析了92例接受药物治疗的精神分裂症患者(包括偏执型(n = 34)、紊乱型(n = 18)和残留型(n = 40))以及50名对照受试者的血浆丙二醛(MDA)水平、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)活性。结果显示,与正常对照组相比,慢性精神分裂症患者的SOD和GSH-Px活性降低,但MDA水平升高。与紊乱型亚型和对照组相比,偏执型和残留型亚型的SOD和GSH-Px活性显著降低。与对照组相比,所有亚型的MDA水平均显著升高。接受氯氮平(n = 44)、利培酮(n = 20)和传统抗精神病药物(n = 28)治疗的所有三个亚组之间,所测任何参数均无显著差异。此外,女性患者的MDA水平显著高于男性,但CAT活性显著低于男性。这些结果表明,氧化应激可能与精神分裂症所有亚型的病理生理学有关,这可能导致膜脂质过氧化增加。长期使用传统和非典型抗精神病药物治疗可能对抗氧化酶和脂质过氧化产生相似的影响。

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