發(fā)布時間：2018-03-13 15:14

  本文選題：精神分裂癥　切入點：糖脂代謝相關(guān)因子　出處：《天津醫(yī)科大學》2013年碩士論文　論文類型：學位論文

【摘要】：目的：精神分裂癥患者在抗精神病藥物治療中伴發(fā)的糖脂代謝異常及相關(guān)問題日益凸現(xiàn),嚴重影響精神疾病的治療,已成為抗精神病藥物臨床治療中的棘手問題。目前普遍認為精神分裂癥治療中出現(xiàn)的糖脂代謝異常是由抗精神病藥引起的,然而,有研究資料證明首發(fā)的、未曾用過抗精神病藥的分裂癥患者存在代謝異常；因此,精神分裂癥是否與代謝障礙存在遺傳共病、抗精神病藥是如何影響糖脂代謝的調(diào)節(jié)卻不清楚。本課題擬通過對首次發(fā)病、未曾用過抗精神病藥物的精神分裂癥患者在抗精神病藥物治療中不同服藥時間內(nèi)糖脂代謝情況進行研究,同時對其家系成員中一級親屬的糖脂代謝進行系統(tǒng)研究,試圖提供精神分裂癥患者伴發(fā)糖脂代謝異常的臨床證據(jù)以及糖脂代謝異常發(fā)生與服藥時間之間的關(guān)系,為精神分裂癥治療過程中伴發(fā)的糖脂代謝異常問題的臨床治療和預防提供理論依據(jù)。 方法：本課題由動物實驗和臨床試驗組成,共分三部分。 第一部分實驗旨在探討抗精神病藥物對正常個體糖脂代謝的影響。本部分試驗采用正常SD大鼠,給予6周的抗精神病藥物(氟哌啶醇組、阿立哌唑組、奧氮平組)觀察,生理鹽水組做對照,觀察用藥后第6周大鼠進食水、體重、GH、COR、Leptin、INS、IGF-1、IGFBP-1、IGFBP-3的變化及各組間的變化。 第二部分試驗旨在探討首發(fā)精神分裂癥患者藥物治療12周后療效及治療期間糖脂代謝水平的變化,并探討與服藥時間之間的關(guān)系。本部分臨床試驗收集首發(fā)精神分裂癥患者61例,觀察比較首次發(fā)病、未曾用過抗精神病藥物的精神分裂癥患者用抗精神病藥物奧氮平治療前、治療開始后第1、4、8、12周末體重指數(shù)、腰圍、血漿血糖、CHOL、TGL、HDL、VLDL等糖脂代謝相關(guān)因子水平變化；同時采用陽性與陰性癥狀量表(PANSS)評定治療前后精神癥狀變化。 第三部分試驗旨在探討精神分裂癥患者的正常一級親屬糖脂代謝情況。本部分收集精神分裂癥患者的正常一級親屬32例,正常人群對照37例,比較精神分裂癥患者一級親屬和正常人群對照腹圍、體重指數(shù)、血漿血糖、胰島素、IGF-1、Leptin以及GH等糖代謝相關(guān)因子水平。 結(jié)果：第一部分：實驗結(jié)果顯示,給予6周抗精神病藥物后,給予奧氮平組大鼠表現(xiàn)出明顯的進食水的增多,差異有統(tǒng)計學意義(P0.05)：給藥三組大鼠血漿GH、COR、Leptin、INS、IGFBP-1、IGFBP-3水平降低,但無統(tǒng)計學差異；給予奧氮平組大鼠血漿的IGF-1水平明顯低于阿立哌唑、氟哌啶醇及生理鹽水各組,差異有統(tǒng)計學意義(P0.05)；阿立哌唑、氟哌啶醇組與生理鹽水組相比,差異無統(tǒng)計學意義(P0.05)。 第二部分：結(jié)果顯示,給予奧氮平12周治療后患者的PANSS總分與治療前相比降低,差異有統(tǒng)計學意義(P0.05)；血漿CHOL、TGL、VLDL水平在4周末便有明顯的升高(P0.01),8周、12周血漿CHOL、TGL、VLDL水平也一直維持在較高的水平。血漿HDL水平在奧氮平治療的4周、8周、12周與治療前均未見明顯的改變,各組間的比較無差異(P0.05)。 第三部分：結(jié)果顯示,精神分裂癥患者正常一級親屬體重指數(shù)、腰圍與正常人群相比,差異無統(tǒng)計學意義(P0.05)；患者正常一級親屬存在明顯的胰島素抵抗,與正常對照組相比,差異有統(tǒng)計學意義(P0.05)；患者正常一級親屬的血漿胰島素水平高于正常對照組,差異有統(tǒng)計學意義(P0.05),但IGF-1水平明顯低于正常對照組,差異有統(tǒng)計學意義(P0.05) 結(jié)論：本研究通過動物實驗和臨床試驗相結(jié)合,探討了首發(fā)精神分裂癥患者在抗精神病藥物治療中伴發(fā)的糖脂代謝水平。主要結(jié)論如下： (1)抗精神病藥物可能影響正常個體的糖脂代謝水平,其中非典型抗精神病藥奧氮平對糖脂代謝的影響更明顯。 (2)奧氮平明顯改善精神病性癥狀,在為期12周的奧氮平治療中PANSS量表評分明顯減低,提示奧氮平作為首發(fā)精神分裂癥患者治療的首選用藥,療效明顯；在奧氮平治療后的第4周,脂代謝的相關(guān)因子指標明顯增高,在給藥后的8周、12周始終維持在較高水平。 (3)精神分裂癥患者正常一級親屬血漿胰島素水平明顯高于正常對照組,IGF-1明顯的低于正常對照組,提示精神分裂癥一級親屬存在糖脂代謝異常的高危因素。 總之,本研究通過動物實驗和臨床觀察,觀察到抗精神病藥物對正常大鼠糖脂代謝的影響,同時,臨床試驗則采用單一用藥(奧氮平)治療首發(fā)、未用藥的精神分裂癥患者,并分別在不同的治療時間段檢測其血漿糖脂代謝水平,可以更為準確全面的評價精神分裂癥患者治療中伴發(fā)的糖脂代謝的變化。本研究為精神分裂癥治療過程中伴發(fā)的代謝障礙問題的臨床治療和預防提供了理論依據(jù)。
[Abstract]:Objective: in patients with schizophrenia antipsychotics are associated with abnormal glucose and lipid metabolism and related problems have become increasingly prominent, seriously affected the treatment of mental illness, has become a thorny problem in clinical treatment of psychiatric drugs. It is generally believed that the resistance in glucose and lipid metabolism in schizophrenia however appear in the treatment of abnormal is caused by antipsychotics medicine, research data show that, first, never used antipsychotic drugs for schizophrenia patients with metabolic disorders; therefore, schizophrenia and metabolic disorders are genetic diseases, antipsychotics is how to influence lipid metabolism regulation is not clear. The aim of this episode for the first time and never used antipsychotic drugs for schizophrenia research spirit of glycolipid metabolism in patients with different medication time in antipsychotic drug treatment, at the same time of first-degree relatives of family members in the Glucose and lipid metabolism were studied, to provide the relationship between the schizophrenia patients associated with abnormal glucose and lipid metabolism and clinical evidence of abnormal glucose and lipid metabolism and medication time, clinical treatment and prognosis of abnormal glucose and lipid metabolism for the treatment of schizophrenia in the process associated with the prevention and provide a theoretical basis.
Methods: the subject was composed of animal experiments and clinical trials, which were divided into three parts.
The first part of the experiment was designed to investigate the effects of antipsychotic drugs on lipid metabolism in normal individuals. This part of the test with normal SD rats were given antipsychotic drugs for 6 weeks (haloperidol group, aripiprazole, olanzapine group) were observed, the normal saline group as control group, observe the drug sixth weeks after rats were fed with water, weight GH, COR, Leptin, INS, IGF-1, IGFBP-1, and IGFBP-3, the changes between the groups.
The second part of the first experiment was to investigate the changes of patients with schizophrenia drug metabolism of glucose and lipid levels during treatment and 12 weeks after treatment, and to explore the relationship between time and medication. The collection of clinical trials in first-episode schizophrenic patients in 61 cases, were compared between the first onset, had never used antipsychotic drugs in schizophrenia patients with the antipsychotic olanzapine before treatment, after treatment after 1,4,8,12 week BMI, waist circumference, blood glucose, CHOL, TGL, HDL, factor level changes related to glucose and lipid metabolism in VLDL; at the same time, the positive and negative symptoms scale (PANSS) changes of psychiatric symptoms were assessed before and after treatment.
The third part experiment was conducted to investigate schizophrenia in first-degree relatives with normal glucose and lipid metabolism in patients with the situation. This part of the collection of schizophrenic patients with normal first-degree relatives of 32 cases, 37 cases of normal control group, comparison of first-degree relatives of schizophrenic patients and normal controls abdominal circumference, body weight index, plasma glucose, insulin, IGF-1. The level of glucose metabolism related factors Leptin and GH.
Results: the first part: the experimental results show that with 6 weeks of antipsychotics, olanzapine group rats showed significantly increased intake of food and water, the difference was statistically significant (P0.05): Administration of plasma GH, COR in the three groups of rats, Leptin, INS, IGFBP-1, IGFBP-3 levels decreased, but no significant difference; olanzapine group rats received plasma IGF-1 levels were significantly lower than aripiprazole, haloperidol and saline groups, the difference was statistically significant (P0.05); aripiprazole, haloperidol group compared with the saline group, the difference was not statistically significant (P0.05).
The second part: the results showed that olanzapine 12 weeks after treatment PANSS score and treatment of patients with lower than before, the difference was statistically significant (P0.05); plasma CHOL, TGL, VLDL level in the 4 weekend was significantly increased (P0.01), 8 weeks, 12 weeks of plasma CHOL, TGL, VLDL level has been maintained at a high level. The level of plasma HDL in olanzapine in the treatment of 4 weeks, 8 weeks, 12 weeks before and after treatment showed no obvious change between groups were no difference (P0.05).
The third part: the results showed that patients with schizophrenia in first-degree relatives with normal BMI, waist circumference compared with the control group, the difference was not statistically significant (P0.05); patients with normal first-degree relatives have obvious insulin resistance, compared with the normal control group, the difference was statistically significant (P0.05); plasma insulin levels in patients with normal first-degree relatives the higher than the normal control group, the difference was statistically significant (P0.05), but the level of IGF-1 was significantly lower than the normal control group, the difference was statistically significant (P0.05)
Conclusion: This study explored the glucose and lipid metabolism in first-episode schizophrenics treated with antipsychotic drugs through animal experiments and clinical trials.
(1) antipsychotic drugs may affect the level of glycolipid metabolism in normal individuals, and the atypical antipsychotic olanzapine has a more obvious effect on glycolipid metabolism.
(2) olanzapine significantly improved psychotic symptoms in olanzapine in the treatment of 12 weeks in the PANSS score decreased significantly, suggesting that the drug of choice, olanzapine as patients with first-episode schizophrenia treatment significantly; at fourth weeks after treatment with olanzapine, factors related to lipid metabolism index increased significantly after the administration of 8 weeks, 12 weeks is always maintained at a high level.
(3) the plasma insulin level of the first-degree relatives of schizophrenic patients is significantly higher than that of the normal control group. IGF-1 is significantly lower than that of the normal control group, suggesting that there is a high risk factor of abnormal glucose and lipid metabolism in first-degree relatives of schizophrenia.
In conclusion, this study by animal experiment and clinical observation, to observe effects of antipsychotic drugs on lipid metabolism in normal rats at the same time, clinical trials using single drug (olanzapine) treatment of first-episode, drug naive schizophrenic patients, and to detect the level of plasma glucose and lipid metabolism in different treatment time, can a more accurate and comprehensive evaluation of changes in glucose and lipid metabolism in patients with schizophrenia treated with hair. Provide a theoretical basis for clinical treatment and prevention of metabolic disorders the research for schizophrenia treatments are associated with.

【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R749.3

【引證文獻】

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2 陳景華;;阿立哌唑與奧氮平治療首發(fā)精神分裂癥療效及對糖脂代謝影響[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2015年21期

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本文編號：1606939