基于社会—心理因素对卵巢储备功能下降的因、机、证、治研究
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摘要
目的：本研究拟通过临床调查、动物实验及临床观察等手段,基于社会-心理因素,进行卵巢储备功能下降的因、机、证、治研究,探讨社会-心理因素与卵巢储备功能下降的关系。
方法：①通过流行病学调查,与健康人群对照,评估卵巢储备功能下降患者患者的社会心理现状；②采取不可预测的多因子刺激手段交替作用于雌性大鼠,使其对大鼠产生慢性精神应激作用。干预结束后,对各组大鼠连续一周每日定时作阴道检查,观察大鼠的动情周期。并量取大鼠卵巢体积；光镜下观测各级卵泡发育情况；化学发光法检测血清E2,放免法检测血清FSH;we s tern blot法检测卵巢颗粒细胞caspases-3、Apaf-1表达水平,以观察慢性精神应激对卵巢储备功能的影响,并探讨其可能机制；③通过对卵巢储备功能下降患者患者主诉、中医诊断及辨证情况进行分析统计,探讨卵巢储备功能下降患者的临床表现特征及辨证规律；④选择肾虚肝郁型卵巢储备功能下降患者,通过自身前后对照的方法,观察补肾舒肝中药治疗月经后期、月经过少的临床疗效。
结果：
①相较于正常女性,卵巢储备功能下降患者中吸烟者较多(P<0.05),脑力劳动者多(P<0.05),且“自觉工作压力大”(P<0.05)。卵巢储备功能下降患者SCL-90总分、总均分、阳性项目数、阳性症状均分、人际敏感、抑郁、焦虑、偏执及神经质方面,均高于正常女性(P<0.05)
Q CUMS法造模大鼠体质量增长较少,食欲减退,旷场实验提示大鼠水平及垂直活动均减少,大鼠糖水偏好度明显降低(P<0.05)。大鼠动情周期延长,21d平均动情次数减少,为3-4次(P<0.01)。E2表达水平下降,FSH表达水平升高(P<0.05)。卵巢Apaf-1.Caspase-3表达水平均升高(P<0.05)。HE染色：各级卵泡数量少,卵泡液含量减少,颗粒细胞层数减少,卵丘变形或消失,趋于闭锁；部分组织见血管扩张,有不同程度的炎细胞浸润。
@111例卵巢储备功能下降患者主诉症状出现率为：不孕(41.44%)>月经量少(36.04%)>月经周期提前(33.33%)>月经周期后错(29.73%)>月经量多(3.60%)>不规则出血(1.80%)。中医诊断顺序依次为：月经过少(46.85%)>月经后期(45.05%)>不孕(39.64%)>月经先期(16.22%)>闭经(7.21%)>月经过多(3.60%)>崩漏(1.80%)。证型分布频次为：肾虚肝郁(45.95%)>肾虚血瘀(28.83%)>肝肾阴虚(8.11%)>脾肾两虚(6.31%)>气滞血瘀(4.50%)>痰湿凝滞(2.70%)。
④经治疗,痊愈3人,显效21人,有效12人,无效10人,愈显率达52.17%,总有效率达78.26%。患者症状总改善比达60.91%(P<0.01)。单项症状包括：月经量少、月经后期、乳房胀痛、腰膝酸软、经色黯红、有血块、胸胁胀痛,时叹息、少腹胀痛、头晕耳呜症状,均较治疗前明显改善,(P≤0.1). FS H. FSH/LH水平明显下降,差异显著(P<0.05)。
结论：
①卵巢储备功能下降患者中,吸烟者、脑力劳动者,以及自觉工作压力大者较正常女性多,患者存在焦虑、担心,有强烈的情绪反应,难以适应外部环境等性格因素,以及人际敏感、焦虑、抑郁、神经质及偏执等不良社会心理因素。推测不良的社会-心理因素与卵巢储备功能下降的发病有关；
②慢性精神应激可导致雌性大鼠血FSH升高,E2降低,卵泡数量减少、质量降低,卵巢储备功能下降；
③慢性精神应激可导致雌性大鼠卵巢组织Caspase-3.Apaf-1的表达,推测促进卵巢组织凋亡可能是慢性精神应激导致卵巢储备功能下降的机制之一；
④“月经过少”、“月经后期”、“不孕”、“月经先期”是卵巢储备功能下降患者最常见的临床表现；肾虚肝郁型、肾虚血瘀型是卵巢储备功能下降的主要临床证型；
⑤香生调经饮治疗D0R肾虚肝郁型月经过少、月经后期愈显率达52.17%,总有效率78.26%,可明显降调基础FSH. FSH/LH水平。
Objective:To study the relationship between social-psychological factors and diminished ovarian reserve, Explore the syndrome distribution rules of diminished ovarian reserve, and evaluate the efficacy of DOR by Tranditional Chinese Medicine.
Methods:①Assess the psychosocial situat ion of diminished ovarian reserve patients by clinical research;②Sexually mature female Wistar rats were randomly divided into experimental and control groups. The simulation of chronic mental stress with chronic mild unpredictable stress (CUMS) depress the rats, Detect estradiol (E2) and follicle stimulating hormone (FSH) level in serum, as well as ovarian Biopsy; and caspases-3, Apaf-1expression levels of ovarian were detected by western blot, to explore the pathogenesis of DOR with psychosocial factors;③Analysis the frequency of Chief complaints and symptoms of diminished ovarian reserve patients, to explore the syndrome distribution rules;④Compared the symptoms score before and after treatment,to observe the efficacy DOR by TCM.
Results:
①There are more smokers, and mental workers,with more consciously work pressure in diminished ovarian reserve patients,compared with other females (P<0.05). The total and mean score, number of positive items of SCL-90were higher than healthy women (P<0.05). DOR patients acts more interpersonal sensitivity, depression, anxiety, paranoia and nervousness (P<0.05).
②Serum E2levels decreased, and FSH levels increased in experimental group, compared with the control group, with significant differences (P<0.05). While in the experimental group, all levels of the number of follicles in the ovary, the number of luteal, follicular fluid, granulosa cell layers was significantly reduced than in the control group, and with varying degrees of blood vessels to dilate. Apaf-1and Caspase-3of ovarian expressed increased (P<0.05).
③111cases DOR patients were observed, the frequency of chief complaints:infertility (41.44%)> Hypomenorrhea (36.04%)> early menstruation (33.33%)> Delayed menstruation (29.73%). the frequency of symptoms:hypomenorrhea (46.85%)> Delayed menstruation (45.05%)> infertility (39.64%)> early menstruation (16.22%)> amenorrhea (7.21%)> menorrhagia (3.60%). the frequency of symptoms:Kidney Deficiency and Liver Stagnation (45.95%)> kidney deficiency and blood stasis (28.83%)> Liver-kidney yin Deficiency (8.11%)> deficiency of spleen and kidney (6.31%)> Qi stagnation and blood stasis (4.50%).
④46cases were observed, after treatment,3people were cured,21were markedly effective,12were Effective,and10were invalid. Markedly effective rate was52.17%, the total effective rate was78.26%. The score of patient's symptoms was improved60.91%after TCM than before (P<0.01). Symptoms include:menstruation, delayed menstruation, breast pain, weak waist,and so on. FSH, FSH/LH levels were significantly decreased(P <0.05).
Conclus ion:
①There are more smokers, and mental workers,with more consciously work pressure in diminished ovarian reserve patients.There is a strong emotional reaction, anxiety, worry, difficult to adapt to the external environment, personality factors, and also interpersonal sensitivity in DOR patients,and negative social and psychological factors such as anxiety, depression, nervousness and paranoia. Maybe that poor social-psychological factors are associated with the incidence of diminished ovarian reserve;
〤hronic mental stress can lead to elevated serum FSH, reduced E2, and decrease in the number and quality of follicles in female rats, decline in ovarian reserve;
〤hronic mental stress can lead to reduced the expression of Caspase-3and Apaf-lovar ian in female rats, Maybe that promote apoptosis of ovarian tissue with chronic mental stress is one of the mechanisms of leads to diminished ovarian reserve;
﹉ypomenorrhea, delayed menstruation, infertility, early menstruation are the the most common clinical manifestations of DOR patients; Kidney Deficiency and Liver Stagnation, Kidney deficiency and blood stasis is a major clinical syndrome type of diminished ovarian reserve;
⑤The markedly effective rate of diminished ovarian reserve patients by TCM treatment is50.17%,and the total efficiency is78.26%. TCM treatment can also Reduce the expression of FSH and FSH/LH.
方法：①通过流行病学调查,与健康人群对照,评估卵巢储备功能下降患者患者的社会心理现状；②采取不可预测的多因子刺激手段交替作用于雌性大鼠,使其对大鼠产生慢性精神应激作用。干预结束后,对各组大鼠连续一周每日定时作阴道检查,观察大鼠的动情周期。并量取大鼠卵巢体积；光镜下观测各级卵泡发育情况；化学发光法检测血清E2,放免法检测血清FSH;we s tern blot法检测卵巢颗粒细胞caspases-3、Apaf-1表达水平,以观察慢性精神应激对卵巢储备功能的影响,并探讨其可能机制；③通过对卵巢储备功能下降患者患者主诉、中医诊断及辨证情况进行分析统计,探讨卵巢储备功能下降患者的临床表现特征及辨证规律；④选择肾虚肝郁型卵巢储备功能下降患者,通过自身前后对照的方法,观察补肾舒肝中药治疗月经后期、月经过少的临床疗效。
结果：
①相较于正常女性,卵巢储备功能下降患者中吸烟者较多(P<0.05),脑力劳动者多(P<0.05),且“自觉工作压力大”(P<0.05)。卵巢储备功能下降患者SCL-90总分、总均分、阳性项目数、阳性症状均分、人际敏感、抑郁、焦虑、偏执及神经质方面,均高于正常女性(P<0.05)
Q CUMS法造模大鼠体质量增长较少,食欲减退,旷场实验提示大鼠水平及垂直活动均减少,大鼠糖水偏好度明显降低(P<0.05)。大鼠动情周期延长,21d平均动情次数减少,为3-4次(P<0.01)。E2表达水平下降,FSH表达水平升高(P<0.05)。卵巢Apaf-1.Caspase-3表达水平均升高(P<0.05)。HE染色：各级卵泡数量少,卵泡液含量减少,颗粒细胞层数减少,卵丘变形或消失,趋于闭锁；部分组织见血管扩张,有不同程度的炎细胞浸润。
@111例卵巢储备功能下降患者主诉症状出现率为：不孕(41.44%)>月经量少(36.04%)>月经周期提前(33.33%)>月经周期后错(29.73%)>月经量多(3.60%)>不规则出血(1.80%)。中医诊断顺序依次为：月经过少(46.85%)>月经后期(45.05%)>不孕(39.64%)>月经先期(16.22%)>闭经(7.21%)>月经过多(3.60%)>崩漏(1.80%)。证型分布频次为：肾虚肝郁(45.95%)>肾虚血瘀(28.83%)>肝肾阴虚(8.11%)>脾肾两虚(6.31%)>气滞血瘀(4.50%)>痰湿凝滞(2.70%)。
④经治疗,痊愈3人,显效21人,有效12人,无效10人,愈显率达52.17%,总有效率达78.26%。患者症状总改善比达60.91%(P<0.01)。单项症状包括：月经量少、月经后期、乳房胀痛、腰膝酸软、经色黯红、有血块、胸胁胀痛,时叹息、少腹胀痛、头晕耳呜症状,均较治疗前明显改善,(P≤0.1). FS H. FSH/LH水平明显下降,差异显著(P<0.05)。
结论：
①卵巢储备功能下降患者中,吸烟者、脑力劳动者,以及自觉工作压力大者较正常女性多,患者存在焦虑、担心,有强烈的情绪反应,难以适应外部环境等性格因素,以及人际敏感、焦虑、抑郁、神经质及偏执等不良社会心理因素。推测不良的社会-心理因素与卵巢储备功能下降的发病有关；
②慢性精神应激可导致雌性大鼠血FSH升高,E2降低,卵泡数量减少、质量降低,卵巢储备功能下降；
③慢性精神应激可导致雌性大鼠卵巢组织Caspase-3.Apaf-1的表达,推测促进卵巢组织凋亡可能是慢性精神应激导致卵巢储备功能下降的机制之一；
④“月经过少”、“月经后期”、“不孕”、“月经先期”是卵巢储备功能下降患者最常见的临床表现；肾虚肝郁型、肾虚血瘀型是卵巢储备功能下降的主要临床证型；
⑤香生调经饮治疗D0R肾虚肝郁型月经过少、月经后期愈显率达52.17%,总有效率78.26%,可明显降调基础FSH. FSH/LH水平。
Objective:To study the relationship between social-psychological factors and diminished ovarian reserve, Explore the syndrome distribution rules of diminished ovarian reserve, and evaluate the efficacy of DOR by Tranditional Chinese Medicine.
Methods:①Assess the psychosocial situat ion of diminished ovarian reserve patients by clinical research;②Sexually mature female Wistar rats were randomly divided into experimental and control groups. The simulation of chronic mental stress with chronic mild unpredictable stress (CUMS) depress the rats, Detect estradiol (E2) and follicle stimulating hormone (FSH) level in serum, as well as ovarian Biopsy; and caspases-3, Apaf-1expression levels of ovarian were detected by western blot, to explore the pathogenesis of DOR with psychosocial factors;③Analysis the frequency of Chief complaints and symptoms of diminished ovarian reserve patients, to explore the syndrome distribution rules;④Compared the symptoms score before and after treatment,to observe the efficacy DOR by TCM.
Results:
①There are more smokers, and mental workers,with more consciously work pressure in diminished ovarian reserve patients,compared with other females (P<0.05). The total and mean score, number of positive items of SCL-90were higher than healthy women (P<0.05). DOR patients acts more interpersonal sensitivity, depression, anxiety, paranoia and nervousness (P<0.05).
②Serum E2levels decreased, and FSH levels increased in experimental group, compared with the control group, with significant differences (P<0.05). While in the experimental group, all levels of the number of follicles in the ovary, the number of luteal, follicular fluid, granulosa cell layers was significantly reduced than in the control group, and with varying degrees of blood vessels to dilate. Apaf-1and Caspase-3of ovarian expressed increased (P<0.05).
③111cases DOR patients were observed, the frequency of chief complaints:infertility (41.44%)> Hypomenorrhea (36.04%)> early menstruation (33.33%)> Delayed menstruation (29.73%). the frequency of symptoms:hypomenorrhea (46.85%)> Delayed menstruation (45.05%)> infertility (39.64%)> early menstruation (16.22%)> amenorrhea (7.21%)> menorrhagia (3.60%). the frequency of symptoms:Kidney Deficiency and Liver Stagnation (45.95%)> kidney deficiency and blood stasis (28.83%)> Liver-kidney yin Deficiency (8.11%)> deficiency of spleen and kidney (6.31%)> Qi stagnation and blood stasis (4.50%).
④46cases were observed, after treatment,3people were cured,21were markedly effective,12were Effective,and10were invalid. Markedly effective rate was52.17%, the total effective rate was78.26%. The score of patient's symptoms was improved60.91%after TCM than before (P<0.01). Symptoms include:menstruation, delayed menstruation, breast pain, weak waist,and so on. FSH, FSH/LH levels were significantly decreased(P <0.05).
Conclus ion:
①There are more smokers, and mental workers,with more consciously work pressure in diminished ovarian reserve patients.There is a strong emotional reaction, anxiety, worry, difficult to adapt to the external environment, personality factors, and also interpersonal sensitivity in DOR patients,and negative social and psychological factors such as anxiety, depression, nervousness and paranoia. Maybe that poor social-psychological factors are associated with the incidence of diminished ovarian reserve;
〤hronic mental stress can lead to elevated serum FSH, reduced E2, and decrease in the number and quality of follicles in female rats, decline in ovarian reserve;
〤hronic mental stress can lead to reduced the expression of Caspase-3and Apaf-lovar ian in female rats, Maybe that promote apoptosis of ovarian tissue with chronic mental stress is one of the mechanisms of leads to diminished ovarian reserve;
﹉ypomenorrhea, delayed menstruation, infertility, early menstruation are the the most common clinical manifestations of DOR patients; Kidney Deficiency and Liver Stagnation, Kidney deficiency and blood stasis is a major clinical syndrome type of diminished ovarian reserve;
⑤The markedly effective rate of diminished ovarian reserve patients by TCM treatment is50.17%,and the total efficiency is78.26%. TCM treatment can also Reduce the expression of FSH and FSH/LH.
引文
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