肝气郁结证、肝火上炎证患者情绪测量及与5-HTT，TPH，ACE基因多态性相关研究
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摘要
目的：探讨肝气郁结证，肝火上炎证患者的情绪状态特征及与5-HTT，TPH，ACE基因多态性相关的分子遗传机理。
方法：1、病证结合选择研究对象，按异病同证和同病异证分组，采用中医肝脏象情绪量表及Beck焦虑量表、Beck抑郁量表对203例肝气郁结证、肝火上炎证、肝气虚证、肝阳上亢证患者及90例健康人对照进行情绪测量。2、运用多聚酶链式反应技术(PCR)检测5-HTT启动子区(5-HTTLPR)、5-HTT基因内含子2 VNTR、TPH基因内含子7 A218C及ACE基因插入/缺失(I/D)四种基因多态性在四种中医证型中的分布频率，并与健康人对照组比较。
结果：1、肝气郁结证、肝火上炎证、肝气虚证、肝阳上亢证患者中医肝脏象情绪量表、Beck焦虑量表、Beck抑郁量表测值各项积分均明显高于健康人对照组(P＜0.01)。2、异病同证比较，中医肝脏象情绪量表肝经维度和焦虑维度，肝阳上亢证和肝火上炎证明显高于肝气郁结证和肝气虚证，差异有显著性(P＜0.01)；抑郁维度方面，肝气郁结证明显高于肝阳上亢证组，差异有显著性(P＜0.05)；总分方面，肝火上炎证明显高于肝气虚证，差异有显著性(P＜0.01)。Beck焦虑量表积分，肝火上炎证明显高于肝气郁结证和肝气虚证，差异有显著性(P＜0.01)；Beck抑郁量表积分，肝气郁结证、肝气虚证高于肝阳上亢证(P＜0.01，P＜0.05)。3、神经症同病异证四种中医证型之间比较，中医肝脏象情绪量表肝经维度积分肝阳上亢证和肝火上炎证明显高于肝气虚证(P＜0.01)；焦虑维度及Beck焦虑量表积分，肝火上炎证最高，肝气虚证最低，但四种证型差异无显著性；抑郁维度及Beck抑郁量表积分，肝气郁结证高于肝阳上亢证(P＜0.01，P＜0.05)。4、5-HTTLPR基因多态性分布频率异病同证比较，肝火上炎证、肝阳上亢证患者组与健康人组基因型分布频率差
异有显著性（HO．026，HO．025人 两证的钻基因型频率明显高于
健康人组02伽S49儿 69VS49肋；肝火上炎证患者组与健康人组等
位基因频率差异有显著性（HO 009人 肝火上炎证患者的S等位基
因频率明显高于健康人组抢5伽S71趾；神经症同病异证比较结果类
似，肝火上炎证、肝阳上亢证患者组的SS基因型频率明显高于健康
人组（80％VS49％HO．021，72VS49％ HO．009）；肝火上炎证患者的 S
等位基因频率明显高于健康人组瞩8伽S71％HO．015人肝气郁结证、
肝气虚证患者组与健康人组比较各基因型和等位基因频率均差异无
显著性（ho．05）。5、5－HT基因内含子 2 VNTR、TPH基因内含子 7 A218C
及 ACE内含子 161川型多态性在四种中医证型中的分布频率无显著
性差异（NO．05人
结论：1、肝气郁结证、肝火上炎证及其对照证候肝气虚证、肝
阳上亢证患者均具有不同程度的焦虑、抑郁情绪状态。2、肝火上炎
证和肝阳上亢证患者的焦虑程度要高于肝气郁结证和肝气虚证患
者。3、肝气郁结证患者的抑郁程度要高于肝阳上亢证患者。4、
5干TTLPR多态性％型个体可能是肝火上炎证和肝阳上亢证的易感
人群。
Objective To explore the emotional characteristics of patients with hepatic depression syndrome and hyperpyrexia of liver syndrome and the relationship between the syndroms and polymorphisms in the serotonin transporter(5-HTT), tryptophan hydroxylase(TPH), and angiotensin converting enzyme(ACE) genes
Methods 1. The patients were selected by considering not only their western medicine diagnosis but also their Traditional Chinese Medicine (TCM) diagnosis. Their emotion state were measured with Emotions Rating Scale for Ganzangxiang of traditional Chinese medicine(ERSG), Beck anxiety inventory(BAI) and Beck depression inventory (BDI) in 90 healthy subjects and 203 patients with hepatic depression syndrome, hyperpyrexia of liver syndrome, deficiency of hepatic Qi syndrome, or hyperhepatic Yang syndrome.
2. Using a polymerase chain reaction-based technique, the frequencies of 5-HTTLPR, 5-HTT intron2 VNTR, TPH intron7 A218C, and ACE intron 16 insertion/deletion (I/D) polymorphisms were determined in all patient groups and control subjects. Genotype and allele frequency comparisons between patient groups and control subjects were carried out with chi-square tests or Fisher's exact tests.
Results 1. The accumulating scores of three dimensions in ERSG, BAI and BDI of all patients were significantly higher than that of controls (PO.01) .
2. When comparisons were carried out in all patients with different syndrome of TCM, the scores of Ganjing dimension and anxiety dimension in ERSG were higher in patients with hyperhepatic Yang
syndrome and hyperpyrexia of liver syndrome than that with deficiency of hepatic Qi syndrome and hepatic depression syndrome (P<0.01); The scores of depression dimension in ERSG were significantly higher in patients with hepatic depression syndrome than that with hyperhepatic Yang syndrome (P<0.01) ; the total scores of ERSG were significantly higher in patients with hyperpyrexia of liver syndrome than that with deficiency of hepatic Qi syndrome (P<0.01) ; the scores of BAI were higher in patients with hyperpyrexia of liver syndrome than that with deficiency of hepatic Qi syndrome and hepatic depression syndrome (P<0.01) ; The scores of BDI were significantly higher in patients with hepatic depression syndrome and deficiency of hepatic Qi syndrome than that with hyperhepatic Yang syndrome (P<0.01, P<0.05) .
3. When comparation were carried out in neurosis patients, the scores of Ganjing dimension in ERSG were higher in patients with hyperhepatic Yang syndrome and hyperpyrexia of liver syndrome than that with deficiency of hepatic qi syndrome. The scores of anxiety dimension in ERSG and BAI were similar in patients with four liver syndromes. The scores of depression dimension in ERSG and BDI were significantly higher in patients with hepatic depression syndrome than that with hyperhepatic Yang syndrome.
4. When comparisons were carried out in all patients with different syndrome of TCM, the frequencies of 5-HTTLPR short/short (SS) genotype were significantly higher in patients with hyperpyrexia of liver syndrome and hyperhepatic Yang syndrome than in control subjects (72%vs49%, P=0.026; 69vs49%, P=0.025), and the S allele frequencies were significantly higher in patients with hyperpyrexia of liver syndrome than in control subjects(85% vs 71%, P=0.009). Similar
results were observed when comparation were carried out in neurosis patients, the frequencies of 5-HTTLPR short/short (SS) genotype were significantly higher in patients with hyperpyrexia of liver syndrome and hyperhepatic Yang syndrome than in control subjects (80%vs49%, P=0.021; 72vs49%, P=0.009), and the S allele frequencies were significantly higher in patients with hyperpyrexia of liver syndrome than in control subjects(88% vs 71%, P=0.015). However, there were no differences for the distribution of 5-HTTLPR between patients with deficiency of hepatic Qi syndrome and hepatic depression syndrome and controls.
5. No significant differences for the genotype distribution or the allele frequency of 5-HTT intr
方法：1、病证结合选择研究对象，按异病同证和同病异证分组，采用中医肝脏象情绪量表及Beck焦虑量表、Beck抑郁量表对203例肝气郁结证、肝火上炎证、肝气虚证、肝阳上亢证患者及90例健康人对照进行情绪测量。2、运用多聚酶链式反应技术(PCR)检测5-HTT启动子区(5-HTTLPR)、5-HTT基因内含子2 VNTR、TPH基因内含子7 A218C及ACE基因插入/缺失(I/D)四种基因多态性在四种中医证型中的分布频率，并与健康人对照组比较。
结果：1、肝气郁结证、肝火上炎证、肝气虚证、肝阳上亢证患者中医肝脏象情绪量表、Beck焦虑量表、Beck抑郁量表测值各项积分均明显高于健康人对照组(P＜0.01)。2、异病同证比较，中医肝脏象情绪量表肝经维度和焦虑维度，肝阳上亢证和肝火上炎证明显高于肝气郁结证和肝气虚证，差异有显著性(P＜0.01)；抑郁维度方面，肝气郁结证明显高于肝阳上亢证组，差异有显著性(P＜0.05)；总分方面，肝火上炎证明显高于肝气虚证，差异有显著性(P＜0.01)。Beck焦虑量表积分，肝火上炎证明显高于肝气郁结证和肝气虚证，差异有显著性(P＜0.01)；Beck抑郁量表积分，肝气郁结证、肝气虚证高于肝阳上亢证(P＜0.01，P＜0.05)。3、神经症同病异证四种中医证型之间比较，中医肝脏象情绪量表肝经维度积分肝阳上亢证和肝火上炎证明显高于肝气虚证(P＜0.01)；焦虑维度及Beck焦虑量表积分，肝火上炎证最高，肝气虚证最低，但四种证型差异无显著性；抑郁维度及Beck抑郁量表积分，肝气郁结证高于肝阳上亢证(P＜0.01，P＜0.05)。4、5-HTTLPR基因多态性分布频率异病同证比较，肝火上炎证、肝阳上亢证患者组与健康人组基因型分布频率差
异有显著性（HO．026，HO．025人 两证的钻基因型频率明显高于
健康人组02伽S49儿 69VS49肋；肝火上炎证患者组与健康人组等
位基因频率差异有显著性（HO 009人 肝火上炎证患者的S等位基
因频率明显高于健康人组抢5伽S71趾；神经症同病异证比较结果类
似，肝火上炎证、肝阳上亢证患者组的SS基因型频率明显高于健康
人组（80％VS49％HO．021，72VS49％ HO．009）；肝火上炎证患者的 S
等位基因频率明显高于健康人组瞩8伽S71％HO．015人肝气郁结证、
肝气虚证患者组与健康人组比较各基因型和等位基因频率均差异无
显著性（ho．05）。5、5－HT基因内含子 2 VNTR、TPH基因内含子 7 A218C
及 ACE内含子 161川型多态性在四种中医证型中的分布频率无显著
性差异（NO．05人
结论：1、肝气郁结证、肝火上炎证及其对照证候肝气虚证、肝
阳上亢证患者均具有不同程度的焦虑、抑郁情绪状态。2、肝火上炎
证和肝阳上亢证患者的焦虑程度要高于肝气郁结证和肝气虚证患
者。3、肝气郁结证患者的抑郁程度要高于肝阳上亢证患者。4、
5干TTLPR多态性％型个体可能是肝火上炎证和肝阳上亢证的易感
人群。
Objective To explore the emotional characteristics of patients with hepatic depression syndrome and hyperpyrexia of liver syndrome and the relationship between the syndroms and polymorphisms in the serotonin transporter(5-HTT), tryptophan hydroxylase(TPH), and angiotensin converting enzyme(ACE) genes
Methods 1. The patients were selected by considering not only their western medicine diagnosis but also their Traditional Chinese Medicine (TCM) diagnosis. Their emotion state were measured with Emotions Rating Scale for Ganzangxiang of traditional Chinese medicine(ERSG), Beck anxiety inventory(BAI) and Beck depression inventory (BDI) in 90 healthy subjects and 203 patients with hepatic depression syndrome, hyperpyrexia of liver syndrome, deficiency of hepatic Qi syndrome, or hyperhepatic Yang syndrome.
2. Using a polymerase chain reaction-based technique, the frequencies of 5-HTTLPR, 5-HTT intron2 VNTR, TPH intron7 A218C, and ACE intron 16 insertion/deletion (I/D) polymorphisms were determined in all patient groups and control subjects. Genotype and allele frequency comparisons between patient groups and control subjects were carried out with chi-square tests or Fisher's exact tests.
Results 1. The accumulating scores of three dimensions in ERSG, BAI and BDI of all patients were significantly higher than that of controls (PO.01) .
2. When comparisons were carried out in all patients with different syndrome of TCM, the scores of Ganjing dimension and anxiety dimension in ERSG were higher in patients with hyperhepatic Yang
syndrome and hyperpyrexia of liver syndrome than that with deficiency of hepatic Qi syndrome and hepatic depression syndrome (P<0.01); The scores of depression dimension in ERSG were significantly higher in patients with hepatic depression syndrome than that with hyperhepatic Yang syndrome (P<0.01) ; the total scores of ERSG were significantly higher in patients with hyperpyrexia of liver syndrome than that with deficiency of hepatic Qi syndrome (P<0.01) ; the scores of BAI were higher in patients with hyperpyrexia of liver syndrome than that with deficiency of hepatic Qi syndrome and hepatic depression syndrome (P<0.01) ; The scores of BDI were significantly higher in patients with hepatic depression syndrome and deficiency of hepatic Qi syndrome than that with hyperhepatic Yang syndrome (P<0.01, P<0.05) .
3. When comparation were carried out in neurosis patients, the scores of Ganjing dimension in ERSG were higher in patients with hyperhepatic Yang syndrome and hyperpyrexia of liver syndrome than that with deficiency of hepatic qi syndrome. The scores of anxiety dimension in ERSG and BAI were similar in patients with four liver syndromes. The scores of depression dimension in ERSG and BDI were significantly higher in patients with hepatic depression syndrome than that with hyperhepatic Yang syndrome.
4. When comparisons were carried out in all patients with different syndrome of TCM, the frequencies of 5-HTTLPR short/short (SS) genotype were significantly higher in patients with hyperpyrexia of liver syndrome and hyperhepatic Yang syndrome than in control subjects (72%vs49%, P=0.026; 69vs49%, P=0.025), and the S allele frequencies were significantly higher in patients with hyperpyrexia of liver syndrome than in control subjects(85% vs 71%, P=0.009). Similar
results were observed when comparation were carried out in neurosis patients, the frequencies of 5-HTTLPR short/short (SS) genotype were significantly higher in patients with hyperpyrexia of liver syndrome and hyperhepatic Yang syndrome than in control subjects (80%vs49%, P=0.021; 72vs49%, P=0.009), and the S allele frequencies were significantly higher in patients with hyperpyrexia of liver syndrome than in control subjects(88% vs 71%, P=0.015). However, there were no differences for the distribution of 5-HTTLPR between patients with deficiency of hepatic Qi syndrome and hepatic depression syndrome and controls.
5. No significant differences for the genotype distribution or the allele frequency of 5-HTT intr
引文
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