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1.中国中医科学院 中医基础理论研究所,北京 100700
2.北京航天总医院,北京 100076
3.首都医科大学 中医药学院,北京 100069
4.广州中医药大学,广州 510006
李玉波,博士,副研究员,从事情志病、生殖类疾病的中医基础与临床研究,Tel:010-64089032,E-mail:liyubo123456@126.com
* 苗青,博士后,助理研究员,从事中医方证基础研究,Tel:010-64089019,E-mail:mmdj2013@126.com;
王伟,博士,教授,博士生导师,从事中西医结合治疗心血管病、糖尿病并发症的机制与新药研究;心血管病的证治规律研究,Tel:020-39358233,E-mail:wangwei@gzucm.edu.cn
收稿日期:2021-07-28,
网络出版日期:2021-10-18,
纸质出版日期:2021-12-05
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李玉波,于眉,李君玲等.方剂反证在构建病证结合动物模型中的作用[J].中国实验方剂学杂志,2021,27(23):44-50.
LI Yu-bo,YU Mei,LI Jun-ling,et al.Role of Counterevidence from Chinese Medicinal Prescription in Construction of Integrated Disease-syndrome Animal Model: Xiaoyaosan as Counterevidence for Depression of Liver Depression and Spleen Deficiency Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(23):44-50.
李玉波,于眉,李君玲等.方剂反证在构建病证结合动物模型中的作用[J].中国实验方剂学杂志,2021,27(23):44-50. DOI: 10.13422/j.cnki.syfjx.20212391.
LI Yu-bo,YU Mei,LI Jun-ling,et al.Role of Counterevidence from Chinese Medicinal Prescription in Construction of Integrated Disease-syndrome Animal Model: Xiaoyaosan as Counterevidence for Depression of Liver Depression and Spleen Deficiency Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(23):44-50. DOI: 10.13422/j.cnki.syfjx.20212391.
目的
2
通过方剂反证寻找病证结合动物模型的证候稳定时间窗,并验证证候的稳定可靠性。
方法
2
采用慢性不可预知温和应激(CUMS)法并通过体质量测量、糖水消耗实验、行为学实验、脑组织5-羟色胺(5-HT)检测建立大鼠抑郁症模型,通过人类临床症状等效转化为大鼠宏观表征等方法来进行大鼠的肝郁脾虚证的证候判别,基于宏观表征动态采集量表用逍遥散反证抑郁症肝郁脾虚证病证结合动物模型的稳定可靠性。
结果
2
大鼠16周龄时,CUMS组(应激8周)大鼠糖水消耗量、旷场实验穿格次数和活动总距离均明显低于正常组(
P
<
0.05);免疫组化结果显示,CUMS组大鼠脑组织海马CA2区5-HT含量也明显低于正常组(
P
<
0.05),说明抑郁症疾病的模型制作成功。CUMS组大鼠肝郁脾虚证出现于14周龄(应激后6周),16周龄(应激后8周)时数量达到最大值占比约70%,往后数量逐渐下降。方剂反证CUMS组14,16,18,20,22周龄大鼠证候积分分别减少66.6%,70.7%,54.8%,50.4%,44.8%,证候疗效分别为有效、显效、有效、有效、有效。
结论
2
CUMS组大鼠14~16周龄即CUMS 6~8周是抑郁症肝郁脾虚证稳定可靠的时间窗。
Objective
2
To seed for stable time window of the integrated disease-syndrome animal model based on the counterevidence from Chinese medicinal prescriptions, and to verify syndrome stability and reliability.
Method
2
A model of depression was established by exposing rats to chronic unpredictable mild stress (CUMS), followed by body weight measurement, sugar water test, behavioral test, and brain 5-hydroxytryptamine(5-HT) detection. The identification of liver depression and spleen deficiency syndrome was conducted after the equivalent transformation of human clinical symptoms into macroscopic representations of rats. Based on the dynamically collected macroscopic representation scale, Xiaoyaosan was used to reversely verify the stability and reliability of the integrated disease-syndrome animal model of depression due to liver depression and spleen deficiency.
Result
2
The sugar water consumption and the number of crossings and the total movement distance in the open field test of 16-week-old rats in the CUMS (eight weeks of CUMS) group were significantly lower than those in the normal group (
P
<
0.05). According to the immunohistochemical results, the 5-HT content in hippocampal area CA2 of rats in the CUMS group was also significantly lowered as compared with that in the normal group(
P
<
0.05),which indicated that depression was successfully modeled. The liver depression and spleen deficiency syndrome was present in 14-week-old rats (six weeks after CUMS)of the CUMS group, and the number of rats experiencing the liver depression and spleen deficiency syndrome reached the peak in the 16th week (eight weeks after CUMS),accounting for 70% of the total number. Thereafter, the number decreased gradually. The syndrome scores of the 14-, 16-, 18-, 20-, and 22-week-old rats in the Xiaoyaosan group were reduced by 66.6%, 70.7%, 54.8%, 50.4%, and 44.8%, which were graded as effective, marked effective, effective, effective, and effective, respectively.
Conclusion
2
The age of 14-16 weeks(six to eight weeks after CUMS) is considered the stable and reliable time window for depression due to liver depression and spleen deficiency.
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