DRD2-PI3K-AKT信号通路基因表达水平在精神分裂症发病机制及糖脂代谢中的作用
发布时间：2018-10-18 12:54
【摘要】：目的：探讨急性期精神分裂症患者多巴胺D2受体及其下游细胞内信号转导通路关键基因PI3K、AKT在外周血白细胞中的mRNA表达水平，并分析其与精神病性症状、糖脂代谢的关系，研究其在精神分裂症诊疗过程中的价值。 方法：于2011年7月至2012年9月间在无锡市精神卫生中心入组急性期精神分裂症住院患者24例，慢性期长期住院病人19例，正常对照21例。以real-timeRT PCR的方法检测多巴胺受体D2（dopamine receptor D2，DRD2）、丝氨酸/苏氨酸蛋白激酶Akt（serine/threonine protein kinase Akt， AKT）、磷脂酰肌醇3-激酶（Phosphoinositide3-kinase，PI3K）基因在外周血白细胞中的信使核糖核酸（Messenger RNA，mRNA）表达水平，同时检测其血浆糖脂代谢的相关生化指标，并以阳性和阴性症状量表（Positive and Negative Syndrome Scale，PANSS）评定患者的精神病性症状。分析急性期精神分裂症患者DRD2、AKT、PI3K基因在外周血白细胞中的mRNA表达水平与其精神病性症状、糖脂代谢的关系。 结果：在急性期组与正常对照组的血清表达量中，DRD2（F=102.73，P=0.00）及PI3K(F=2.30，P=0.11)均存在显著差异，将DRD2与PI3K的慢性期与正常对照组的对比，，则不存在显著差异。AKT的急性期组与正常对照组不存在显著差异，慢性期组与正常对照组有显著差异（F=16.71，P=0.00）。在糖代谢方面，急性期组的空腹胰岛素（t=4.25，P=0.00）和餐后2小时胰岛素（t=3.10，P=0.01）都与正常对照组有着显著差异。而空腹血糖、餐后2小时血糖以及空腹C肽和餐后2小时C肽等指标的急性组与正常对照组之间无差异。而急性期的HOMA-IR与PI3K、与AKT以及DRD2之间的表达未见明确的相关性。同时，急性期的HOMA-IR与正常人的值相比较，也没有明显差异。在脂代谢方面，可以看到四项急性期组的指标只有甘油三酯与正常对照组没有显著的差异，另外三项关于脂代谢的总胆固醇（t=4.00，P=0.00）、HDL（t=7.77，P=0.00）及LDL（t=2.62，P=0.01）在急性期组与正常组之间都有着显著性差异。在PANSS量表的得分与基因表达量方面，可以明确发现，量表的得分与基因的表达不存在明确的线性相关。 结论：急性期精神分裂症患者外周血的PI3K、AKT及DRD2基因表达水平都与正常人群存在着显著差异。但其基因的表达量与患者所表现出来的症状并无明确的相关关系。此外，精神分裂症病人在糖脂代谢方面均存在一定的异常，这提示着DRD2-PI3K-AKT信号通路在精神分裂症发病机制和糖脂代谢中发挥重要作用。
[Abstract]:Objective: to investigate the expression of dopamine D2 receptor and its downstream signal transduction pathway gene PI3K,AKT in peripheral blood leukocytes in patients with acute schizophrenia, and to analyze the relationship between the expression of mRNA and psychiatric symptoms, glucose and lipid metabolism. To study its value in the diagnosis and treatment of schizophrenia. Methods: from July 2011 to September 2012, 24 patients with acute schizophrenia, 19 patients with chronic schizophrenia and 21 normal controls were enrolled in Wuxi Mental Health Center. The expression of dopamine receptor D2 (dopamine receptor D2DRD2, serine / threonine protein kinase Akt (serine/threonine protein kinase Akt, AKT), phosphatidylinositol 3-kinase (Phosphoinositide3-kinase,PI3K) gene) in peripheral white blood cells (PBWs) was detected by real-timeRT PCR. At the same time, the related biochemical indexes of plasma glucose and lipid metabolism were detected, and the psychiatric symptoms were assessed by positive and negative symptom scale (Positive and Negative Syndrome Scale,PANSS). To analyze the relationship between the expression of DRD2,AKT,PI3K gene mRNA in peripheral blood leukocytes and psychotic symptoms, glucose and lipid metabolism in patients with acute schizophrenia. Results: in the acute phase group and the normal control group, there were significant differences in the serum expression levels of DRD2 (FG 102.73) and PI3K (FN 2.30 P0. 11). The chronic phase of DRD2 and PI3K was compared with that of the normal control group. There was no significant difference in AKT between the acute phase group and the normal control group, but there was significant difference between the chronic phase group and the normal control group. In terms of glucose metabolism, fasting insulin (tb4.25m) and postprandial insulin (t 3.10g / P0.01) in the acute phase group were significantly different from those in the normal control group. There was no significant difference in fasting blood glucose, postprandial blood glucose, fasting C-peptide and 2-hour postprandial C-peptide between the acute group and the normal control group. However, the expression of HOMA-IR, PI3K, AKT and DRD2 in acute stage was not positively correlated. At the same time, there was no significant difference in HOMA-IR between the acute stage and the normal subjects. In the aspect of lipid metabolism, it can be seen that only triglyceride has no significant difference between the four acute phase groups and the normal control group, and the other three items of total cholesterol (t 4. 00), HDL () and LDL (t 2. 62% P0. 01) are significantly different between the acute phase group and the normal group. In the aspect of PANSS score and gene expression, it is clear that there is no linear correlation between the score and gene expression. Conclusion: the expression levels of PI3K,AKT and DRD2 genes in peripheral blood of patients with acute schizophrenia are significantly different from those of normal controls. However, there was no clear correlation between gene expression and symptoms. In addition, there are some abnormalities in glucose and lipid metabolism in schizophrenic patients, which suggests that DRD2-PI3K-AKT signaling pathway plays an important role in the pathogenesis of schizophrenia and glycolipid metabolism.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.3
本文编号：2279186
[Abstract]:Objective: to investigate the expression of dopamine D2 receptor and its downstream signal transduction pathway gene PI3K,AKT in peripheral blood leukocytes in patients with acute schizophrenia, and to analyze the relationship between the expression of mRNA and psychiatric symptoms, glucose and lipid metabolism. To study its value in the diagnosis and treatment of schizophrenia. Methods: from July 2011 to September 2012, 24 patients with acute schizophrenia, 19 patients with chronic schizophrenia and 21 normal controls were enrolled in Wuxi Mental Health Center. The expression of dopamine receptor D2 (dopamine receptor D2DRD2, serine / threonine protein kinase Akt (serine/threonine protein kinase Akt, AKT), phosphatidylinositol 3-kinase (Phosphoinositide3-kinase,PI3K) gene) in peripheral white blood cells (PBWs) was detected by real-timeRT PCR. At the same time, the related biochemical indexes of plasma glucose and lipid metabolism were detected, and the psychiatric symptoms were assessed by positive and negative symptom scale (Positive and Negative Syndrome Scale,PANSS). To analyze the relationship between the expression of DRD2,AKT,PI3K gene mRNA in peripheral blood leukocytes and psychotic symptoms, glucose and lipid metabolism in patients with acute schizophrenia. Results: in the acute phase group and the normal control group, there were significant differences in the serum expression levels of DRD2 (FG 102.73) and PI3K (FN 2.30 P0. 11). The chronic phase of DRD2 and PI3K was compared with that of the normal control group. There was no significant difference in AKT between the acute phase group and the normal control group, but there was significant difference between the chronic phase group and the normal control group. In terms of glucose metabolism, fasting insulin (tb4.25m) and postprandial insulin (t 3.10g / P0.01) in the acute phase group were significantly different from those in the normal control group. There was no significant difference in fasting blood glucose, postprandial blood glucose, fasting C-peptide and 2-hour postprandial C-peptide between the acute group and the normal control group. However, the expression of HOMA-IR, PI3K, AKT and DRD2 in acute stage was not positively correlated. At the same time, there was no significant difference in HOMA-IR between the acute stage and the normal subjects. In the aspect of lipid metabolism, it can be seen that only triglyceride has no significant difference between the four acute phase groups and the normal control group, and the other three items of total cholesterol (t 4. 00), HDL () and LDL (t 2. 62% P0. 01) are significantly different between the acute phase group and the normal group. In the aspect of PANSS score and gene expression, it is clear that there is no linear correlation between the score and gene expression. Conclusion: the expression levels of PI3K,AKT and DRD2 genes in peripheral blood of patients with acute schizophrenia are significantly different from those of normal controls. However, there was no clear correlation between gene expression and symptoms. In addition, there are some abnormalities in glucose and lipid metabolism in schizophrenic patients, which suggests that DRD2-PI3K-AKT signaling pathway plays an important role in the pathogenesis of schizophrenia and glycolipid metabolism.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.3
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1 罗尹;DRD2-PI3K-AKT信号通路基因表达水平在精神分裂症发病机制及糖脂代谢中的作用[D];皖南医学院;2013年
本文编号：2279186
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