养阴舒肝法治疗女性“怒”伤内分泌失调的临床及实验研究
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摘要
目的：
怒作为一种负性情绪,对人的身心产生不良影响,并且严重阻碍人与人之间的情感交流,破坏友谊、爱情、家庭关系。诸多研究显示怒易引起女性生殖内分泌的改变,继而引发诸多妇科内分泌疾病,如闭经、月经紊乱、不孕症、经前期综合征、无排卵、卵巢早衰等。中药治疗不仅能改善怒的症状,而且对纠正这种怒情绪引起的内分泌失调有着良好的效果。本研究旨在探索养阴舒肝法对肝郁气滞月经失调患者的改善作用,及进一步探究养阴舒肝法治疗“怒”伤致内分泌紊乱的机制,为临床养阴舒肝法的应用及养阴舒肝胶囊的应用提供理论基础及依据。
方法：
临床研究：采用随机对照的临床试验设计,纳入2011年10月至2012年2月在广东省中医院妇科门诊就诊的月经不调患者56例,按就诊顺序随机分为2组：治疗组和对照组,其中治疗组收集病例26例,对照组26例。两组各服中药8周,治疗前、治疗4周后、8周后分别进行一次SCL90量表、月经情况评定,并在治疗前后检测血清FSH,E2的浓度和卵巢基础窦卵泡数,同时检测血、尿常规、肝肾功能、心电图等一般安全性项目,填写观察表,记录不良反应。实验研究：分6部分进行。第一部分“怒”对雌性大鼠行为学影响的评估及比较,分别观察了正常组、模型组、养阴舒肝胶囊低、中、高剂量组五组的水平运动、垂直运动及旷场实验总分情况。第二部分“怒”对雌性大鼠生殖内分泌的影响,观察比较五组大鼠AMH、INHB、E2的情况；第三部分“怒”对雌性大鼠脑神经递质的影响,观察比较五组大鼠海马区的5-HT、5-HIAA、NE、 DA的含量：第四部分“怒”对雌性大鼠下丘脑-卵巢雌激素受体的影响,观察比较五组大鼠下丘脑、卵巢ERβ积分光密度；第五部分养阴舒肝胶囊对大鼠心、肝、肾形态学的影响,观察服用养阴舒肝胶囊4周后大鼠心肝肾形态学改变；第六部分养阴舒肝胶囊对大鼠血清ALT、CR的影响,观察服用不同剂量养阴舒肝胶囊4周后大鼠血清ALT、CR改变。
成果：
1.临床疗效比较：根据对月经情况治疗前后的比较进行临床疗效评价,以痊愈、显著进步、进步均为有效计算,得出治疗组的总有效率为84.62%,对照组有效率为84.62%；组间比较,差异无统计学意义(P>0.05),说明治疗组和对照组的疗效相当(P>0.05)。据对敌对因子各症状条目治疗前后比较：两组在易烦恼和激动、不能控制地发脾气两方面评分均下降,差异有统计学意义(P<0.05),两组间差异无统计学意义,说明两组对怒敌对症状的改善作用相当。
2.SCL-90敌对因子总分比较：治疗4周与治疗前SCL-90量表敌对因子总分的比较：组内比较,两组治疗4周后SCL-90敌对因子总分均下降,但治疗组差异无统计学意义(P>0.05),对照组差异有统计学意义(P<0.05)；组间比较,差异无统计学意义(P>0.05),说明服药治疗4周后,两组敌对因子总分均下降,但下降幅度无明显差升。
治疗4周与治疗8周SCL-90量表敌对因子总分的比较：组内比较,两组治疗8周后较治疗4周时SCL-90敌对因子总分均下降,但治疗组差异有显著性(P<0.05),对照组差异无统计学意义(P>0.05)；组间比较,差异无统计学意义(P>0.05),说明服药治疗8周后较4周时,两组敌对因子总分均下降,但下降幅度无明显差异。
治疗8周与治疗前SCL-90量表敌对因子总分的比较：组内比较,两组差异均有显著性(P<0.05),说明两组治疗8周后较治疗前SCL-90敌对因子总分均显著下降；组间比较,差异无统计学意义(P>0.05),说明服药治疗8周后与治疗前比较,两组敌对因子总分均下降,但下降幅度无明显差异。
3.治疗前后FSH、E2、窦卵泡数比较：治疗前后血清FSH、E2含量、窦卵泡计数相比,治疗组和对照组组内比较,差异均无显著性(P>0.05)；组间比较,差异无显著性(P>0.05),提示两组治疗前后,血清性激素检测值、窦卵泡数均无明显变化。
4.两组治疗前后均未见明显(严重)不良反应,安全性检测均未见异常。
5.各组大鼠行为学测试结果：旷场实验：与正常对照组比较,“怒”模型组水平得分、垂直得分、总分均增高,垂直得分和总分差异具有显著性(P<0.01)；与模型组相比较,中药高剂量组与中药中剂量组水平得分下降,差异有统计学意义(P<0.05),总分降低,差异有显著性(P<0.01)；垂直得分降低,与高剂量组间差异有显著性(P<0.01),与中剂量组间差异有统计学意义(P<0.05),中药低剂量组垂直得分降低,差异具有显著性(P<0.01)；水平得分、总分差异无统计学意义(P>0.05)；各给药组相比较,中药低剂量组水平得分较中药中剂量组增高,差异有统计学意义(P<0.05)；中药低剂量组较中药高、中剂量组总分均增高,差异有统计学意义(P<0.05)。
与正常对照组相比较,模型组中央格时间、粪便粒数增多,修饰次数、修饰时间减少,差异具有显著性(P<0.01)；中药低剂量组中央格时间增高、修饰次数减低,差异有统计学意义(P<0.05),修饰时间、粪便粒数差异无统计学意义(P>0.05)；中药中剂量组中央格时间增多,差异有统计学意义(P<0.05)；与模型组相比较,中药高剂量组中央格时间减低,差异有显著性(P<0.01)、粪便粒数减低,修饰次数、修饰时间增多,差异有统计学意义(P<0.05)；中药中剂量组中央格时间减低、差异有显著性(P<0.01),粪便粒数减低,修饰次数增多,差异有统计学意义(P<0.05)；各给药组相比较,中药高、中剂量组较中药低剂量组中央格时间减少,差异有显著性(P<0.01),修饰次数、修饰时间、粪便粒数差异无统计学意义(P>0.05)。
6.各组大鼠血清AMH、 INHB、E2含量比较结果：
AMH含量五组间比较：模型组与正常组、高、中剂量组间存在差异,差异有显著性(P<0.01)；模型组与低剂量组间差异有统计学意义(P<0.05)；正常组与高剂量组间差异有统计学意义(P<0.05)；高剂量与中剂量组间差异有统计学意义(P<0.05)。
INHB含量五组间比较：模型组与正常组、高、中、低剂量组间差异具有显著性(P<0.01)；正常组与高剂量组间差异有统计学意义(P<0.05)；高、中剂量组间差异有统计学意义(P<0.05)。
E2含量五组间比较：模型组与正常组、高、低剂量组间差异具有显著性(P<0.01)；模型组与中剂量组间差异有统计学意义(P<0.05)。
7.各组大鼠海马区脑神经递质比较：
海马NE含量比较：与正常对照组相比较,模型组大鼠海马NE含量明显增高,差异具有显著性(P<0.01)；中药中、低剂量组含量升高,差异具有显著性(P<0.01)；中药高剂量组差异无统计学意义(P>0.05)。与模型组相比较,各给药组NE含量降低,中药高剂量组差异具有显著性(P<0.01)；中药中、低剂量组差异无统计学意义(P>0.05)。各给药组相比较,中药高剂量组NE含量较中、低剂量组低,差异有显著性(P<0.01)；中药中、低剂量组间差异无统计学意义(P>0.05)。
海马DA含量比较：与正常对照组相比较,模型组DA含量增高,差异具有显著性(P<0.01)；中药中、低剂量组含量升高,差异具有统计学意义(P<0.05)；中药高剂量组差异无统计学意义(P>0.05)。与模型组相比较,中药高剂量组含量降低,差异具有显著性(P<0.01)；中药中、低剂量组差异无统计学意义(P>0.05)。各给药组相比较差异无统计学意义(P>0.05)。
海马5-HT含量比较：与正常对照组相比较,模型组5-HT含量增高,差异有显著性(P<0.01)；中药低剂量组显著增高,差异有显著性(P<0.01)；中药高、中剂量组差异无统计学意义(P>0.05)。与模型组相比较,中药高、中剂量组含量降低,差异有统计学意义(P<0.05)；低剂量组差异无统计学意义(P>0.05)。各给药组相比较,中药高、中剂量组较低剂量组含量降低,差异有统计学意义(P<0.05)。
海马区5-HIAA含量五组间比较：模型组与正常组差异有统计学意义(P<0.05)；模型组与高剂量组间差异具有显著性(P<0.01)；高剂量与低剂量组间差异有统计学意义(P<0.05)。
8.各组大鼠下丘脑-卵巢ERβ积分光密度比较结果：
下丘脑ERβ IOD：与正常对照组相比较,模型组下丘脑ERβ积分光密度下降,差异无统计学意义(P>0.05)；与模型组相比较,各给药组下丘脑ER β积分光密度增加,中药低剂量组差异有统计学意义(P<0.05)；中药中、高剂量组差异无统计学意义(P>0.05)；各给药组相比较,差异无统计学意义(P>0.05)。
卵巢ERβ IOD：与正常对照组相比较,模型组、低剂量组卵巢ERβ积分光密度下降,但差异无统计学意义(P>0.05)；与模型组相比较,各给药组卵巢ERβ积分光密度增加,中药高剂量组差异具有统计学意义(P<0.05)；中药中、低剂量组差异无统计学意义(P>0.05)。各给药组相比较,中药高剂量组ERβ积分光密度较中、低剂量组高,高、低剂量组间差异有统计学意义(P<0.05)；中药中、低剂量组间差异无统计学意义(P>0.05)。
9.各组大鼠心、肝、肾组织形态结果显示：养阴舒肝胶囊低、中、高浓度剂量均未见异常。
10.各组大鼠血清ALT、 CR比较结果：养阴舒肝胶囊中、高浓度组ALT比正常组稍高但差异无统计学意义(P>0.05)。养阴舒肝胶囊高浓度组CR较正常组稍高,差异无统计学意义(P>0.05)。
结论：
1.养阴舒肝汤与逍遥散对肝郁气滞型月经失调患者的月经情况及易烦恼激动、不能控制地发脾气的症状均有明显改善作用,两者疗效相当。
2.养阴舒肝汤与逍遥散均能降低SCL90敌对因子总分,在治疗8周后效果最显著,与治疗前存在明显差异。两组间疗效相当。两药对血清FSH、E2、窦卵泡数的改善均不明显。
3.在行为学试验中,大鼠经“怒”应激后水平得分和垂直得分均显著增高,大鼠兴奋性、敏感性增强,探究活动增多。而大鼠离开中央格的时间减慢,其活动迟钝,表明激怒应激后大鼠的空间认知能力降低。修饰时间及修饰次数降低,排便粒数增多,反映激怒后大鼠对新环境的适应能力减弱,紧张程度增加。养阴舒肝胶囊可以降低水平得分、垂直得分、旷场试验总分,减少中央格时间、粪便粒数,增多修饰次数,表明养阴舒肝胶囊对怒情绪导致的过度兴奋及紧张情绪有明显缓解作用。
4.经“怒”应激后的大鼠E2、INHB、 AMH含量均较正常组降低,提示大鼠经怒不良情绪应激后卵巢功能受损。养阴舒肝胶囊各剂量组AMH、 INHB、E2含量均较“怒”模型组增高,提示养阴舒肝胶囊对卵巢功能有一定的恢复作用。其中高剂量组AMH、INHB含量较正常对照组稍有增高,而E2含量则接近正常组水平,考虑可能与养阴舒肝胶囊短期内能明显促进卵巢窦前和小窦状卵泡发育有关,当然亦不排除实验及检测误差带来的可能,尚需进一步研究证实。
5.经“怒”应激后大鼠海马区NE、 DA、5-HT、5-HIAA均升高,可能与怒不良情绪的应激,导致神经内分泌失调有关；经养阴舒肝胶囊干预后发现,高浓度剂量组明显降低海马区4种递质的含量,而中剂量组能明显降低5-HT含量。考虑高剂量浓度的养阴舒肝胶囊对改善“怒”应激引起的神经内分泌的改变作用为更好。
6.经“怒”不良应激后大鼠下丘脑、卵巢ER β积分光密度均下降,但差异无统计学意义,表明经“怒”不良应激后大鼠下丘脑、卵巢生殖内分泌功能轻微受损,经养阴舒肝胶囊药物治疗后下丘脑、卵巢ERβ积分光密度不同程度的恢复至正常水平。且低剂量养阴舒肝胶囊使下丘脑ER β积分光密度显著升高,高剂量养阴舒肝胶囊使卵巢ERβ积分光密度显著升高。考虑下丘脑对养阴舒肝胶囊的药物起效作用可能先于卵巢。
7.经对服用养阴舒肝胶囊的大鼠进行心肝肾形态学及血清ALT、 CR的检测发现,大鼠服用3种浓度剂量的养阴舒肝胶囊4周后均未出现心肝肾组织器官的功能损伤；提示3种浓度剂量的养阴舒肝胶囊均在对大鼠未造成损害的安全范围内。
本文通过临床研究发现养阴舒肝汤对肝郁气滞型月经失调患者的月经改善及烦躁易怒症状的改善作用与逍遥散相当,丰富了临床治疗的内容,增加了患者用药的选择机会。通过动物实验建立情志因素(怒)影响下的育龄期雌性大鼠模型,观察到其行为学、内分泌、神经递质及雌激素受体方面的改变,初步提示在“怒”不良情绪影响下女性易出现行为情绪异样甚至会发生神经、生殖内分泌紊乱。中药养阴舒肝胶囊可缓解“怒”引起的兴奋紧张情绪,并对生殖内分泌、神经递质等方面的异常变化具有改善作用,从而使失调的机体内环境回归稳定；全文结合,为临床运用王教授经验方养阴舒肝胶囊(养阴舒肝汤)治疗女性“怒”情绪相关疾病提供了理论依据。研究提示养阴舒肝胶囊高剂量浓度的效果可能优于中低浓度剂量,并且治疗8周未见心肝肾重要器官的病理改变,所以目前养阴舒肝胶囊合理有效的临床用药剂量可能尚待进一步研究。
Objective
As a negative emotion, anger will affect the physiology and mental hea lty, interrupt emotion communication, friendship, romance and so on. a lot of researches have revealed that anger leads to reproductive endocrine ch anges, and causes to different diseases of reproductive endocrine, such as amenorrhoea, Menstrual disorder, infertility, premenstrual syndrome, prematu re ovarian failure. TCM treatment can not only improve the symptoms of an ger, but also have good effect in correcting endocrine disorders for anger. The aim of paper is to explore the effects of method of nourishing Yin an d discharge Gan in curing menstrual disorders because of liver depression and qi stagnation. And explore mechanism of nourishing Yin and discharge Gan in regulating endocrine disorders for anger, it can provide theoreti cal foundation and basis for Clinical guidance on the application of nour ishing Yin and discharge Gan method.
Methods
Clinical research:a randomized controlled clinical trial design, bri nging in52menstruation disorder patients in Guangdong Province Traditio nal Chinese Medical Hospital from October2011to February2012. Accordin g to the visiting sequence were randomly divided into2groups:The treat ment group, control group, In each group26cases are collected. Both grou ps take medicine for8weeks, patient have a SCL90scale, menstrual situa tion assessment before treatments4weeks after treatment and8weeks aft er treatment. Before and after treatment, Serum FSH, E2concentrations and ovarian antral follicle count are tested. At the same time, blood and uri ne routine, liver and kidney function, electrocardiogram and general secu rity project are also tested. Fill in the watch, recorded adverse reacti on. Experimental study:divided into six parts. The first section:to esti mate and compare behavior of Female rats undergoing anger stress, investi gate horizontal movement, vertical motion, open field test scores of Norm al group, model group, Yangyinshugan capsule groups concluding low, mediu m, or high dose. The second section:the influences of reproductive endoc rine caused by anger stress, observe values of AMH、 INHEB、 E2of five groups of rats. The third section:the influences of Brain neurotransmitter of fe male rats undergoing anger stress, compare with5-HT、5-HIAA、 NE、 DA values in five groups in the hippocampal region;The fourth section:the influen ces of hypothalamus and ovarian estrogen receptor of female rats, observe Integral optical density in the region of hypothalamus and ovary; The fi fth section:to investigate the influences of morphology of heart, liver an d kidney after taking Yangyinshugan capsule4weeks later;The sixth secti on-:to investigate the influences of ALT、 CR in serum caused by Yangyinshu gan capsule in4weeks.
Results
1.Comparison of clinical efficacy:we evaluate clinical effect based o n comparison of menstruation before and after treatment. To heal, remarka ble progress, progress is to efficiently compute, the treatment group in the total efficiency was84.62%, the effective rate of control group was84.62%. Comparison between two groups, the difference was not statistical ly significant (P>0.05), It shows that the treatment group and the contro1group has the similar efficacy, has no significant difference. According to comparison of each symptom items of hostility factor before and after treatment. Two groups has lower score in the symptom of easy worried and excited, unable to control temper after treatment (P<0.05).Two groups h as the similar efficacy in improving the symptom of anger hostility (P<0.05).
2. SCL-90hostility factor total score comparison:SCL-90hostility fac tor total score comparison of treatment for4weeks and before treatment: Within group comparisons, two groups have lower hostility factor total sco re after treatment for4weeks, but the treatment group has no statistical ly significant difference after4weeks treatment (P>0.05).However, the control group has statistically significant difference (P<0.05). Both tw 0groups have lower hostility factor total score after treatment for4we eks, but the decline rate has no significant difference (P>0.05).
SCL-90hostility factor total score comparison of treatment for4wee ks and8weeks:Within group comparisons, two groups have lower hostility factor total score after treatment for8weeks than4weeks, but the contr01group has no statistically significant difference (P>0.05).However, t he treatment group has statistical1-y significant difference (P<0.05). Al so both two groups have lower hostility factor total score after treatmen t for8weeks, but the decline rate has no significant difference(P>0.05).
SCL-90hostility factor total score comparison of treatment for8wee ks and before treatment:Within group comparisons, two groups have signifi cantly lower hostility factor total score after treatment for8weeks tha n before treatment (P<0.05), two groups has no significant difference (P>0.05).
3. Comparison of FSH、E2、 Antral follicle count before and after treatm ent:Within group comparisons, both treatment and control group have no st atistically significant difference before and after treatment (P>0.05); C omparison of each two groups, both have no statistically significant diffe rence before and after treatment (P>0.05).
4.Both treatment and control groups had no obvious (serious) adverse reactions, and safety testing showed no abnormality.
5. Behavior test results:open field experiment:model group has signif icant higher score in horizontal movement, vertical motion compared with normal group (P<0.01); however, compared with model group, high dose grou p and medium group has lower score in horizontal movement (P<0.05), sign ificant lower total sore (P<0.01); Model group has higher score in vertic al motion compared with medium group (P<0.05), significant higher score c ompared with high dose group (P<0.01); low dose group has statistical low er score in vertical motion (P<0.01), no statistical difference in horiz ontal movement score and total score (P>0.05); Low dose group has higher total score than high and medium dose group (P<0.05), and has higher scor e in horizontal movement than medium dose group (P<0.05);
Comparing with normal group,model group has longer central square, mor e fecal pellets, less decorating times (P<0.01); low dose group has longer central square time, less decorating times (P<0.05); medium dose group ha s longer central square time (P<0.05); Comparing with model group, high do se group has fewer central square time (P<0.01), less fecal pellets;more decorating times (P<0.05),medium dose group has fewer central square tim e (P<0.01), decorating times and less fecal pellets (P<0.05);the high and medium doses groups have fewer central square time (P<0.01), no stati stical difference in decorating time, fecal pellets (P>0.05).
6.The results of AMH、INHB、E2content:model group has lower contents in AMH、INHB、E2, compared with normal group (P<0.05), has statistical di fference in AMH、INHB、E2(P<0.01); Compared with model group, high dose group has higher contents in AMH、INHB、E2(P<0.01);Medium group contain s higher contents of AMH、INHB (P<0.01) and higher E2(P<0.05).Low do se has more INHB、 E2(P<0.01) and AMH (P<0.05). High dose group contain s higher contents of AMH、 INHB than medium dose group in all groups (P<0.05)
7.The results of Brain neurotransmitter content of hippocampal regio n:
NE in hippocampal region:compared with normal group,the content of h ippocampal NE in model group, medium, low dose group were higher (P<0.01); Compared with model group, high dose group has lower contents of NE(P<0.01);there were no significant statistical difference in medium, low dose g roups (P>0.05).High dose group has lower contents of NE than medium, low dose groups (P<0.01).
DA in hippocampal:compared with normal group, model group has highes t contents of DA (P<0.01), medium, low dose groups were higher (P<0.05); however,high dose group contains as similar as normal group. Compared wit h model group, high dose group contains less DA than model group(P<0.01); there were no statistical differences between medium, low dose groups and model group.
5-HT in hippocampal:compared with normal group, model and low dose g roups contains more5-HT (P<0.01), whereas high, medium dose groups contai n as similar as normal group. The contents of5-HT in high and medium gro ups were less than model group (P<0.05).No statistical differences displ ay between low dose and model groups (P>0.05). In addition, high and med ium dose groups has less5-HT than low dose group (P<0.05).
5-HIAA in hippocampal:the content of5-HIAA in model group was higher than normal group (P<0.05);the statistical differences existed between high (P<0.01) dose groups and model group.
8. ER β Integral optical density in the region of hypothalamus and ova ry:
Integral optical density in the region of hypothalamus:compared with normal group, the Integral optical density in the model group has no obv iously deduced (P>0.05); Integral optical density in all groups increase d comparing with model group, displaying statistical differences between low dose group (P<0.05), medium, high dose (P>0.05); there were no sta tistical differences among all groups (P>0.05).
Integral optical density in the region of ovary:Integral optical den sity in model group, low dose group declined, compared with normal group, h owever, no statistical differences displayed; compared with model group, Integral optical density in all groups increased,there was statistical di fferences between high dose group and model group (P<0.05). in addition, the high dose group contained more ER βIOD than medium, low dose groups (P <0.05);no statistical differences existed between medium and low dose gr oup (P>0.05).
9. Morphology of heart, liver and kidney in all groups:normal.
10.ALT> CR in serum in all groups:medium, high dose groups contained a bit higher than normal group, but no statistical differences existed (P>0.05). Meanwhile, the content of Cr was a little more than the conte nt in normal group, no statistical differences displayed (P>0.05)
Cone Iusion
1. Yangyinshugan soup and Xiaoyao powder both have good effects in imp roving menstrual disorder and symptom of easy worried and excited, unabl e to control temper, and two groups have the similar effects.
2. Yangyinshugan soup and Xiaoyao powder both can reduce SCL-90hostil ity factor total score. It shows the most significant effect after treatm ent for8weeks, and has significant difference compared to score before treatment. Two groups have the similar effect, have no statistically sign ificant difference. Two groups have no effect in improving FSH、E2、 AFC.
3. In the experiments of behavior, horizontal movement, vertical motio n scores, excitability, sensibility of female rats rised obviously caused by anger stress. However, longer central square time investigated the ra ts have reduced cognitive ability of space. Fewer decorating time, more f ecal pellets reflected weak adaptability to new surrounding, stronger ner vous. Since Yangyinshugan capsule can reduce horizontal, vertical, total score, central square time, fecal pellets, increase decorating frequency, displaying the capsule could relief excitability and tension obviously.
4. AMH、 INHB、 E2contents of rats influenced by anger was lower than no rmal group, which estimated ovarian function impaired after continued imp ulse. AMH、INHB、E2contents of all dose groups were more than model group, displaying the capsule could recover ovarian function to extent, high do se group has higher contents in AMH、 INHB, but E2close to normal level. It may related to the development of ovarian preantral and small antral foil iclesm Also it cannot be ruled out likely the experiment and detection er ror, further research is needed done.
5. NE、DA、5-HT、5-HIAA contents in the area of hippocampal region aris ed clearly because of anger stress, since Yangyinshugan capsule intervene d, high dose group reduced obviously the contents of4kinds of neurotran smitter, while medium group can diminish the content of5-HT\5-HIAA, low dose group can diminish5-HIAA. It shows that all of three groups could r educe content of5-HIAA. We can conclude that high dose group would play an important part on recoving neuroendocrine disorders caused by anger.
6. Integral optical density in the region of hypothalamus and ovary de clined for a long time, caused by anger; which suggested the function of reproductive endocrine impaired, however, Yangyinshugan capsule would be helpful to recover the function to some extent. Low and high dose group c ould rise Integral optical density of hypothalamus and ovary respectively. Different feedback mechanisms would be considered.
7. The changes of morphology of heart, liver and kidney and ALT\CR in serum of rats didn't happen after4weeks, which estimated all kinds of groups would be safe for rats.
According to female rats model influenced by anger, we observed behav ior, endocrine, neurotransmitter and estrogen receptor, which suggested pa thogenesis mechanisms of nerve, reproductive endocrine caused by anger. Ya ngyinshugan capsule would relieve excitability and tension, also can regu late endocrine disorders, so can recover the body environment. It conclud ed from the clinical research that Yangyinshugan soup has the same effect as same as Xiaoyao podwer, which enriched clinical treatment and Increas ed choice. From this paper, It provided a theoretical basis for Yangyinsh ugan capsule in treating "anger" mood related diseases. The experiment s uggested that the effects of high dose group was better than medium, low o nes, and morphology of heart, liver and kidney is normal after treatment f or8weeks. So the the reasonable and effective dosage of Yangyinshugan c apsule maybe need further research.
怒作为一种负性情绪,对人的身心产生不良影响,并且严重阻碍人与人之间的情感交流,破坏友谊、爱情、家庭关系。诸多研究显示怒易引起女性生殖内分泌的改变,继而引发诸多妇科内分泌疾病,如闭经、月经紊乱、不孕症、经前期综合征、无排卵、卵巢早衰等。中药治疗不仅能改善怒的症状,而且对纠正这种怒情绪引起的内分泌失调有着良好的效果。本研究旨在探索养阴舒肝法对肝郁气滞月经失调患者的改善作用,及进一步探究养阴舒肝法治疗“怒”伤致内分泌紊乱的机制,为临床养阴舒肝法的应用及养阴舒肝胶囊的应用提供理论基础及依据。
方法：
临床研究：采用随机对照的临床试验设计,纳入2011年10月至2012年2月在广东省中医院妇科门诊就诊的月经不调患者56例,按就诊顺序随机分为2组：治疗组和对照组,其中治疗组收集病例26例,对照组26例。两组各服中药8周,治疗前、治疗4周后、8周后分别进行一次SCL90量表、月经情况评定,并在治疗前后检测血清FSH,E2的浓度和卵巢基础窦卵泡数,同时检测血、尿常规、肝肾功能、心电图等一般安全性项目,填写观察表,记录不良反应。实验研究：分6部分进行。第一部分“怒”对雌性大鼠行为学影响的评估及比较,分别观察了正常组、模型组、养阴舒肝胶囊低、中、高剂量组五组的水平运动、垂直运动及旷场实验总分情况。第二部分“怒”对雌性大鼠生殖内分泌的影响,观察比较五组大鼠AMH、INHB、E2的情况；第三部分“怒”对雌性大鼠脑神经递质的影响,观察比较五组大鼠海马区的5-HT、5-HIAA、NE、 DA的含量：第四部分“怒”对雌性大鼠下丘脑-卵巢雌激素受体的影响,观察比较五组大鼠下丘脑、卵巢ERβ积分光密度；第五部分养阴舒肝胶囊对大鼠心、肝、肾形态学的影响,观察服用养阴舒肝胶囊4周后大鼠心肝肾形态学改变；第六部分养阴舒肝胶囊对大鼠血清ALT、CR的影响,观察服用不同剂量养阴舒肝胶囊4周后大鼠血清ALT、CR改变。
成果：
1.临床疗效比较：根据对月经情况治疗前后的比较进行临床疗效评价,以痊愈、显著进步、进步均为有效计算,得出治疗组的总有效率为84.62%,对照组有效率为84.62%；组间比较,差异无统计学意义(P>0.05),说明治疗组和对照组的疗效相当(P>0.05)。据对敌对因子各症状条目治疗前后比较：两组在易烦恼和激动、不能控制地发脾气两方面评分均下降,差异有统计学意义(P<0.05),两组间差异无统计学意义,说明两组对怒敌对症状的改善作用相当。
2.SCL-90敌对因子总分比较：治疗4周与治疗前SCL-90量表敌对因子总分的比较：组内比较,两组治疗4周后SCL-90敌对因子总分均下降,但治疗组差异无统计学意义(P>0.05),对照组差异有统计学意义(P<0.05)；组间比较,差异无统计学意义(P>0.05),说明服药治疗4周后,两组敌对因子总分均下降,但下降幅度无明显差升。
治疗4周与治疗8周SCL-90量表敌对因子总分的比较：组内比较,两组治疗8周后较治疗4周时SCL-90敌对因子总分均下降,但治疗组差异有显著性(P<0.05),对照组差异无统计学意义(P>0.05)；组间比较,差异无统计学意义(P>0.05),说明服药治疗8周后较4周时,两组敌对因子总分均下降,但下降幅度无明显差异。
治疗8周与治疗前SCL-90量表敌对因子总分的比较：组内比较,两组差异均有显著性(P<0.05),说明两组治疗8周后较治疗前SCL-90敌对因子总分均显著下降；组间比较,差异无统计学意义(P>0.05),说明服药治疗8周后与治疗前比较,两组敌对因子总分均下降,但下降幅度无明显差异。
3.治疗前后FSH、E2、窦卵泡数比较：治疗前后血清FSH、E2含量、窦卵泡计数相比,治疗组和对照组组内比较,差异均无显著性(P>0.05)；组间比较,差异无显著性(P>0.05),提示两组治疗前后,血清性激素检测值、窦卵泡数均无明显变化。
4.两组治疗前后均未见明显(严重)不良反应,安全性检测均未见异常。
5.各组大鼠行为学测试结果：旷场实验：与正常对照组比较,“怒”模型组水平得分、垂直得分、总分均增高,垂直得分和总分差异具有显著性(P<0.01)；与模型组相比较,中药高剂量组与中药中剂量组水平得分下降,差异有统计学意义(P<0.05),总分降低,差异有显著性(P<0.01)；垂直得分降低,与高剂量组间差异有显著性(P<0.01),与中剂量组间差异有统计学意义(P<0.05),中药低剂量组垂直得分降低,差异具有显著性(P<0.01)；水平得分、总分差异无统计学意义(P>0.05)；各给药组相比较,中药低剂量组水平得分较中药中剂量组增高,差异有统计学意义(P<0.05)；中药低剂量组较中药高、中剂量组总分均增高,差异有统计学意义(P<0.05)。
与正常对照组相比较,模型组中央格时间、粪便粒数增多,修饰次数、修饰时间减少,差异具有显著性(P<0.01)；中药低剂量组中央格时间增高、修饰次数减低,差异有统计学意义(P<0.05),修饰时间、粪便粒数差异无统计学意义(P>0.05)；中药中剂量组中央格时间增多,差异有统计学意义(P<0.05)；与模型组相比较,中药高剂量组中央格时间减低,差异有显著性(P<0.01)、粪便粒数减低,修饰次数、修饰时间增多,差异有统计学意义(P<0.05)；中药中剂量组中央格时间减低、差异有显著性(P<0.01),粪便粒数减低,修饰次数增多,差异有统计学意义(P<0.05)；各给药组相比较,中药高、中剂量组较中药低剂量组中央格时间减少,差异有显著性(P<0.01),修饰次数、修饰时间、粪便粒数差异无统计学意义(P>0.05)。
6.各组大鼠血清AMH、 INHB、E2含量比较结果：
AMH含量五组间比较：模型组与正常组、高、中剂量组间存在差异,差异有显著性(P<0.01)；模型组与低剂量组间差异有统计学意义(P<0.05)；正常组与高剂量组间差异有统计学意义(P<0.05)；高剂量与中剂量组间差异有统计学意义(P<0.05)。
INHB含量五组间比较：模型组与正常组、高、中、低剂量组间差异具有显著性(P<0.01)；正常组与高剂量组间差异有统计学意义(P<0.05)；高、中剂量组间差异有统计学意义(P<0.05)。
E2含量五组间比较：模型组与正常组、高、低剂量组间差异具有显著性(P<0.01)；模型组与中剂量组间差异有统计学意义(P<0.05)。
7.各组大鼠海马区脑神经递质比较：
海马NE含量比较：与正常对照组相比较,模型组大鼠海马NE含量明显增高,差异具有显著性(P<0.01)；中药中、低剂量组含量升高,差异具有显著性(P<0.01)；中药高剂量组差异无统计学意义(P>0.05)。与模型组相比较,各给药组NE含量降低,中药高剂量组差异具有显著性(P<0.01)；中药中、低剂量组差异无统计学意义(P>0.05)。各给药组相比较,中药高剂量组NE含量较中、低剂量组低,差异有显著性(P<0.01)；中药中、低剂量组间差异无统计学意义(P>0.05)。
海马DA含量比较：与正常对照组相比较,模型组DA含量增高,差异具有显著性(P<0.01)；中药中、低剂量组含量升高,差异具有统计学意义(P<0.05)；中药高剂量组差异无统计学意义(P>0.05)。与模型组相比较,中药高剂量组含量降低,差异具有显著性(P<0.01)；中药中、低剂量组差异无统计学意义(P>0.05)。各给药组相比较差异无统计学意义(P>0.05)。
海马5-HT含量比较：与正常对照组相比较,模型组5-HT含量增高,差异有显著性(P<0.01)；中药低剂量组显著增高,差异有显著性(P<0.01)；中药高、中剂量组差异无统计学意义(P>0.05)。与模型组相比较,中药高、中剂量组含量降低,差异有统计学意义(P<0.05)；低剂量组差异无统计学意义(P>0.05)。各给药组相比较,中药高、中剂量组较低剂量组含量降低,差异有统计学意义(P<0.05)。
海马区5-HIAA含量五组间比较：模型组与正常组差异有统计学意义(P<0.05)；模型组与高剂量组间差异具有显著性(P<0.01)；高剂量与低剂量组间差异有统计学意义(P<0.05)。
8.各组大鼠下丘脑-卵巢ERβ积分光密度比较结果：
下丘脑ERβ IOD：与正常对照组相比较,模型组下丘脑ERβ积分光密度下降,差异无统计学意义(P>0.05)；与模型组相比较,各给药组下丘脑ER β积分光密度增加,中药低剂量组差异有统计学意义(P<0.05)；中药中、高剂量组差异无统计学意义(P>0.05)；各给药组相比较,差异无统计学意义(P>0.05)。
卵巢ERβ IOD：与正常对照组相比较,模型组、低剂量组卵巢ERβ积分光密度下降,但差异无统计学意义(P>0.05)；与模型组相比较,各给药组卵巢ERβ积分光密度增加,中药高剂量组差异具有统计学意义(P<0.05)；中药中、低剂量组差异无统计学意义(P>0.05)。各给药组相比较,中药高剂量组ERβ积分光密度较中、低剂量组高,高、低剂量组间差异有统计学意义(P<0.05)；中药中、低剂量组间差异无统计学意义(P>0.05)。
9.各组大鼠心、肝、肾组织形态结果显示：养阴舒肝胶囊低、中、高浓度剂量均未见异常。
10.各组大鼠血清ALT、 CR比较结果：养阴舒肝胶囊中、高浓度组ALT比正常组稍高但差异无统计学意义(P>0.05)。养阴舒肝胶囊高浓度组CR较正常组稍高,差异无统计学意义(P>0.05)。
结论：
1.养阴舒肝汤与逍遥散对肝郁气滞型月经失调患者的月经情况及易烦恼激动、不能控制地发脾气的症状均有明显改善作用,两者疗效相当。
2.养阴舒肝汤与逍遥散均能降低SCL90敌对因子总分,在治疗8周后效果最显著,与治疗前存在明显差异。两组间疗效相当。两药对血清FSH、E2、窦卵泡数的改善均不明显。
3.在行为学试验中,大鼠经“怒”应激后水平得分和垂直得分均显著增高,大鼠兴奋性、敏感性增强,探究活动增多。而大鼠离开中央格的时间减慢,其活动迟钝,表明激怒应激后大鼠的空间认知能力降低。修饰时间及修饰次数降低,排便粒数增多,反映激怒后大鼠对新环境的适应能力减弱,紧张程度增加。养阴舒肝胶囊可以降低水平得分、垂直得分、旷场试验总分,减少中央格时间、粪便粒数,增多修饰次数,表明养阴舒肝胶囊对怒情绪导致的过度兴奋及紧张情绪有明显缓解作用。
4.经“怒”应激后的大鼠E2、INHB、 AMH含量均较正常组降低,提示大鼠经怒不良情绪应激后卵巢功能受损。养阴舒肝胶囊各剂量组AMH、 INHB、E2含量均较“怒”模型组增高,提示养阴舒肝胶囊对卵巢功能有一定的恢复作用。其中高剂量组AMH、INHB含量较正常对照组稍有增高,而E2含量则接近正常组水平,考虑可能与养阴舒肝胶囊短期内能明显促进卵巢窦前和小窦状卵泡发育有关,当然亦不排除实验及检测误差带来的可能,尚需进一步研究证实。
5.经“怒”应激后大鼠海马区NE、 DA、5-HT、5-HIAA均升高,可能与怒不良情绪的应激,导致神经内分泌失调有关；经养阴舒肝胶囊干预后发现,高浓度剂量组明显降低海马区4种递质的含量,而中剂量组能明显降低5-HT含量。考虑高剂量浓度的养阴舒肝胶囊对改善“怒”应激引起的神经内分泌的改变作用为更好。
6.经“怒”不良应激后大鼠下丘脑、卵巢ER β积分光密度均下降,但差异无统计学意义,表明经“怒”不良应激后大鼠下丘脑、卵巢生殖内分泌功能轻微受损,经养阴舒肝胶囊药物治疗后下丘脑、卵巢ERβ积分光密度不同程度的恢复至正常水平。且低剂量养阴舒肝胶囊使下丘脑ER β积分光密度显著升高,高剂量养阴舒肝胶囊使卵巢ERβ积分光密度显著升高。考虑下丘脑对养阴舒肝胶囊的药物起效作用可能先于卵巢。
7.经对服用养阴舒肝胶囊的大鼠进行心肝肾形态学及血清ALT、 CR的检测发现,大鼠服用3种浓度剂量的养阴舒肝胶囊4周后均未出现心肝肾组织器官的功能损伤；提示3种浓度剂量的养阴舒肝胶囊均在对大鼠未造成损害的安全范围内。
本文通过临床研究发现养阴舒肝汤对肝郁气滞型月经失调患者的月经改善及烦躁易怒症状的改善作用与逍遥散相当,丰富了临床治疗的内容,增加了患者用药的选择机会。通过动物实验建立情志因素(怒)影响下的育龄期雌性大鼠模型,观察到其行为学、内分泌、神经递质及雌激素受体方面的改变,初步提示在“怒”不良情绪影响下女性易出现行为情绪异样甚至会发生神经、生殖内分泌紊乱。中药养阴舒肝胶囊可缓解“怒”引起的兴奋紧张情绪,并对生殖内分泌、神经递质等方面的异常变化具有改善作用,从而使失调的机体内环境回归稳定；全文结合,为临床运用王教授经验方养阴舒肝胶囊(养阴舒肝汤)治疗女性“怒”情绪相关疾病提供了理论依据。研究提示养阴舒肝胶囊高剂量浓度的效果可能优于中低浓度剂量,并且治疗8周未见心肝肾重要器官的病理改变,所以目前养阴舒肝胶囊合理有效的临床用药剂量可能尚待进一步研究。
Objective
As a negative emotion, anger will affect the physiology and mental hea lty, interrupt emotion communication, friendship, romance and so on. a lot of researches have revealed that anger leads to reproductive endocrine ch anges, and causes to different diseases of reproductive endocrine, such as amenorrhoea, Menstrual disorder, infertility, premenstrual syndrome, prematu re ovarian failure. TCM treatment can not only improve the symptoms of an ger, but also have good effect in correcting endocrine disorders for anger. The aim of paper is to explore the effects of method of nourishing Yin an d discharge Gan in curing menstrual disorders because of liver depression and qi stagnation. And explore mechanism of nourishing Yin and discharge Gan in regulating endocrine disorders for anger, it can provide theoreti cal foundation and basis for Clinical guidance on the application of nour ishing Yin and discharge Gan method.
Methods
Clinical research:a randomized controlled clinical trial design, bri nging in52menstruation disorder patients in Guangdong Province Traditio nal Chinese Medical Hospital from October2011to February2012. Accordin g to the visiting sequence were randomly divided into2groups:The treat ment group, control group, In each group26cases are collected. Both grou ps take medicine for8weeks, patient have a SCL90scale, menstrual situa tion assessment before treatments4weeks after treatment and8weeks aft er treatment. Before and after treatment, Serum FSH, E2concentrations and ovarian antral follicle count are tested. At the same time, blood and uri ne routine, liver and kidney function, electrocardiogram and general secu rity project are also tested. Fill in the watch, recorded adverse reacti on. Experimental study:divided into six parts. The first section:to esti mate and compare behavior of Female rats undergoing anger stress, investi gate horizontal movement, vertical motion, open field test scores of Norm al group, model group, Yangyinshugan capsule groups concluding low, mediu m, or high dose. The second section:the influences of reproductive endoc rine caused by anger stress, observe values of AMH、 INHEB、 E2of five groups of rats. The third section:the influences of Brain neurotransmitter of fe male rats undergoing anger stress, compare with5-HT、5-HIAA、 NE、 DA values in five groups in the hippocampal region;The fourth section:the influen ces of hypothalamus and ovarian estrogen receptor of female rats, observe Integral optical density in the region of hypothalamus and ovary; The fi fth section:to investigate the influences of morphology of heart, liver an d kidney after taking Yangyinshugan capsule4weeks later;The sixth secti on-:to investigate the influences of ALT、 CR in serum caused by Yangyinshu gan capsule in4weeks.
Results
1.Comparison of clinical efficacy:we evaluate clinical effect based o n comparison of menstruation before and after treatment. To heal, remarka ble progress, progress is to efficiently compute, the treatment group in the total efficiency was84.62%, the effective rate of control group was84.62%. Comparison between two groups, the difference was not statistical ly significant (P>0.05), It shows that the treatment group and the contro1group has the similar efficacy, has no significant difference. According to comparison of each symptom items of hostility factor before and after treatment. Two groups has lower score in the symptom of easy worried and excited, unable to control temper after treatment (P<0.05).Two groups h as the similar efficacy in improving the symptom of anger hostility (P<0.05).
2. SCL-90hostility factor total score comparison:SCL-90hostility fac tor total score comparison of treatment for4weeks and before treatment: Within group comparisons, two groups have lower hostility factor total sco re after treatment for4weeks, but the treatment group has no statistical ly significant difference after4weeks treatment (P>0.05).However, the control group has statistically significant difference (P<0.05). Both tw 0groups have lower hostility factor total score after treatment for4we eks, but the decline rate has no significant difference (P>0.05).
SCL-90hostility factor total score comparison of treatment for4wee ks and8weeks:Within group comparisons, two groups have lower hostility factor total score after treatment for8weeks than4weeks, but the contr01group has no statistically significant difference (P>0.05).However, t he treatment group has statistical1-y significant difference (P<0.05). Al so both two groups have lower hostility factor total score after treatmen t for8weeks, but the decline rate has no significant difference(P>0.05).
SCL-90hostility factor total score comparison of treatment for8wee ks and before treatment:Within group comparisons, two groups have signifi cantly lower hostility factor total score after treatment for8weeks tha n before treatment (P<0.05), two groups has no significant difference (P>0.05).
3. Comparison of FSH、E2、 Antral follicle count before and after treatm ent:Within group comparisons, both treatment and control group have no st atistically significant difference before and after treatment (P>0.05); C omparison of each two groups, both have no statistically significant diffe rence before and after treatment (P>0.05).
4.Both treatment and control groups had no obvious (serious) adverse reactions, and safety testing showed no abnormality.
5. Behavior test results:open field experiment:model group has signif icant higher score in horizontal movement, vertical motion compared with normal group (P<0.01); however, compared with model group, high dose grou p and medium group has lower score in horizontal movement (P<0.05), sign ificant lower total sore (P<0.01); Model group has higher score in vertic al motion compared with medium group (P<0.05), significant higher score c ompared with high dose group (P<0.01); low dose group has statistical low er score in vertical motion (P<0.01), no statistical difference in horiz ontal movement score and total score (P>0.05); Low dose group has higher total score than high and medium dose group (P<0.05), and has higher scor e in horizontal movement than medium dose group (P<0.05);
Comparing with normal group,model group has longer central square, mor e fecal pellets, less decorating times (P<0.01); low dose group has longer central square time, less decorating times (P<0.05); medium dose group ha s longer central square time (P<0.05); Comparing with model group, high do se group has fewer central square time (P<0.01), less fecal pellets;more decorating times (P<0.05),medium dose group has fewer central square tim e (P<0.01), decorating times and less fecal pellets (P<0.05);the high and medium doses groups have fewer central square time (P<0.01), no stati stical difference in decorating time, fecal pellets (P>0.05).
6.The results of AMH、INHB、E2content:model group has lower contents in AMH、INHB、E2, compared with normal group (P<0.05), has statistical di fference in AMH、INHB、E2(P<0.01); Compared with model group, high dose group has higher contents in AMH、INHB、E2(P<0.01);Medium group contain s higher contents of AMH、INHB (P<0.01) and higher E2(P<0.05).Low do se has more INHB、 E2(P<0.01) and AMH (P<0.05). High dose group contain s higher contents of AMH、 INHB than medium dose group in all groups (P<0.05)
7.The results of Brain neurotransmitter content of hippocampal regio n:
NE in hippocampal region:compared with normal group,the content of h ippocampal NE in model group, medium, low dose group were higher (P<0.01); Compared with model group, high dose group has lower contents of NE(P<0.01);there were no significant statistical difference in medium, low dose g roups (P>0.05).High dose group has lower contents of NE than medium, low dose groups (P<0.01).
DA in hippocampal:compared with normal group, model group has highes t contents of DA (P<0.01), medium, low dose groups were higher (P<0.05); however,high dose group contains as similar as normal group. Compared wit h model group, high dose group contains less DA than model group(P<0.01); there were no statistical differences between medium, low dose groups and model group.
5-HT in hippocampal:compared with normal group, model and low dose g roups contains more5-HT (P<0.01), whereas high, medium dose groups contai n as similar as normal group. The contents of5-HT in high and medium gro ups were less than model group (P<0.05).No statistical differences displ ay between low dose and model groups (P>0.05). In addition, high and med ium dose groups has less5-HT than low dose group (P<0.05).
5-HIAA in hippocampal:the content of5-HIAA in model group was higher than normal group (P<0.05);the statistical differences existed between high (P<0.01) dose groups and model group.
8. ER β Integral optical density in the region of hypothalamus and ova ry:
Integral optical density in the region of hypothalamus:compared with normal group, the Integral optical density in the model group has no obv iously deduced (P>0.05); Integral optical density in all groups increase d comparing with model group, displaying statistical differences between low dose group (P<0.05), medium, high dose (P>0.05); there were no sta tistical differences among all groups (P>0.05).
Integral optical density in the region of ovary:Integral optical den sity in model group, low dose group declined, compared with normal group, h owever, no statistical differences displayed; compared with model group, Integral optical density in all groups increased,there was statistical di fferences between high dose group and model group (P<0.05). in addition, the high dose group contained more ER βIOD than medium, low dose groups (P <0.05);no statistical differences existed between medium and low dose gr oup (P>0.05).
9. Morphology of heart, liver and kidney in all groups:normal.
10.ALT> CR in serum in all groups:medium, high dose groups contained a bit higher than normal group, but no statistical differences existed (P>0.05). Meanwhile, the content of Cr was a little more than the conte nt in normal group, no statistical differences displayed (P>0.05)
Cone Iusion
1. Yangyinshugan soup and Xiaoyao powder both have good effects in imp roving menstrual disorder and symptom of easy worried and excited, unabl e to control temper, and two groups have the similar effects.
2. Yangyinshugan soup and Xiaoyao powder both can reduce SCL-90hostil ity factor total score. It shows the most significant effect after treatm ent for8weeks, and has significant difference compared to score before treatment. Two groups have the similar effect, have no statistically sign ificant difference. Two groups have no effect in improving FSH、E2、 AFC.
3. In the experiments of behavior, horizontal movement, vertical motio n scores, excitability, sensibility of female rats rised obviously caused by anger stress. However, longer central square time investigated the ra ts have reduced cognitive ability of space. Fewer decorating time, more f ecal pellets reflected weak adaptability to new surrounding, stronger ner vous. Since Yangyinshugan capsule can reduce horizontal, vertical, total score, central square time, fecal pellets, increase decorating frequency, displaying the capsule could relief excitability and tension obviously.
4. AMH、 INHB、 E2contents of rats influenced by anger was lower than no rmal group, which estimated ovarian function impaired after continued imp ulse. AMH、INHB、E2contents of all dose groups were more than model group, displaying the capsule could recover ovarian function to extent, high do se group has higher contents in AMH、 INHB, but E2close to normal level. It may related to the development of ovarian preantral and small antral foil iclesm Also it cannot be ruled out likely the experiment and detection er ror, further research is needed done.
5. NE、DA、5-HT、5-HIAA contents in the area of hippocampal region aris ed clearly because of anger stress, since Yangyinshugan capsule intervene d, high dose group reduced obviously the contents of4kinds of neurotran smitter, while medium group can diminish the content of5-HT\5-HIAA, low dose group can diminish5-HIAA. It shows that all of three groups could r educe content of5-HIAA. We can conclude that high dose group would play an important part on recoving neuroendocrine disorders caused by anger.
6. Integral optical density in the region of hypothalamus and ovary de clined for a long time, caused by anger; which suggested the function of reproductive endocrine impaired, however, Yangyinshugan capsule would be helpful to recover the function to some extent. Low and high dose group c ould rise Integral optical density of hypothalamus and ovary respectively. Different feedback mechanisms would be considered.
7. The changes of morphology of heart, liver and kidney and ALT\CR in serum of rats didn't happen after4weeks, which estimated all kinds of groups would be safe for rats.
According to female rats model influenced by anger, we observed behav ior, endocrine, neurotransmitter and estrogen receptor, which suggested pa thogenesis mechanisms of nerve, reproductive endocrine caused by anger. Ya ngyinshugan capsule would relieve excitability and tension, also can regu late endocrine disorders, so can recover the body environment. It conclud ed from the clinical research that Yangyinshugan soup has the same effect as same as Xiaoyao podwer, which enriched clinical treatment and Increas ed choice. From this paper, It provided a theoretical basis for Yangyinsh ugan capsule in treating "anger" mood related diseases. The experiment s uggested that the effects of high dose group was better than medium, low o nes, and morphology of heart, liver and kidney is normal after treatment f or8weeks. So the the reasonable and effective dosage of Yangyinshugan c apsule maybe need further research.
引文
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