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1. 北京中医药大学, 北京 100029
2. 国家中医药管理局 名医名方重点研究室, 北京 100029
毕于聪,在读硕士,从事中药新药研发研究,E-mail:byc1206@163.com
王停,博士,研究员,博士生导师,从事中药新药研发研究,E-mail:wangting1973@sina.com
网络出版日期:2020-04-20,
纸质出版日期:2020-07-05
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毕于聪,史渊源,张林等.双金散结颗粒治疗乳腺增生的药效及物质基础[J].中国实验方剂学杂志,2020,26(13):111-117.
BI Yu-cong,SHI Yuan-yuan,ZHANG Lin,et al.Efficacy and Material Basis of Shuangjin Sanjie Granules in Treatment on Hyperplasia of Mammary Gland[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):111-117.
毕于聪,史渊源,张林等.双金散结颗粒治疗乳腺增生的药效及物质基础[J].中国实验方剂学杂志,2020,26(13):111-117. DOI: 10.13422/j.cnki.syfjx.20201328.
BI Yu-cong,SHI Yuan-yuan,ZHANG Lin,et al.Efficacy and Material Basis of Shuangjin Sanjie Granules in Treatment on Hyperplasia of Mammary Gland[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):111-117. DOI: 10.13422/j.cnki.syfjx.20201328.
目的
2
利用乳腺增生SD大鼠模型及超高效液相色谱-高分辨质谱联用(UHPLC-LTQ-Orbitrap MS)技术探讨双金散结颗粒治疗乳腺增生的药效及物质基础。
方法
2
将乳腺增生SD大鼠模型动物分组给药,测量乳头高度及直径,检测血清中雌二醇(E
2
),孕酮(P)及催乳素(PRL)含量,病理学检测乳腺组织增生情况,免疫组化检测雌激素受体
α
(ER
α
),雄激素受体(AR),孕酮受体(PR),肿瘤坏死因子-
α
(TNF-
α
)等蛋白表达,最后用UHPLC-LTQ-Orbitrap MS技术检测双金散结颗粒主要化学成分,与药效结合分析药效物质基础。
结果
2
动物实验结果显示,与正常组比较,模型组乳头高度增加,直径增宽(
P
<
0.01);血清E
2
显著升高(
P
<
0.01);病理学检测表明乳腺组织异常增生;ER
α
,AR,PR,TNF-
α
蛋白表达增加(
P
<
0.01);与模型组比较,双金散结颗粒组乳头高度降低,直径减小(
P
<
0.01);血清E
2
显著下降(
P
<
0.01);病理学检测表明乳腺组织异常增生减弱;ER
α
,AR,PR,TNF-
α
蛋白表达显著降低(
P
<
0.01)。物质基础研究结果显示,从双金散结颗粒中共鉴定出85个化学成分,其中16种化学成分为生物碱类化合物,7种成分为黄酮类化合物,15种为萜类化合物,9种为酚酸类化合物,3种香豆素类化合物,10种酯类及内酯类化合物,7种脂肪酸类化合物,4种氨基酸类化合物和14种其他类成分,其中生物碱类及萜类成分可能与药效作用密切相关。
结论
2
双金散结颗粒可有效改善乳腺增生病变情况,其药效物质基础可能是柴胡皂苷a,d;贝母素甲、乙等成分。
Objective
2
The SD rat model of hyperplasia of mammary gland(HMG) and the ultrahigh-performance liquid chromatography and mass spectrometry (UHPLC-LTQ-Orbitrap MS) technology were used to explore the pharmacological material basis of Shuangjin Sanjie granules (SJSJG) for the treatment on HMG.
Method
2
SD rat models of HMG were administered in groups
and the nipple height and the diameter were measured; the levels of estradiol (E
2
)
progesterone (P) and prolactin (PRL) in serum were detected
pathological examination was conducted for the hyperplasia of breast tissue. Histochemical methods were used to detect the expressions of estrogen receptor
α
(ER
α
)
androgen receptor (AR)
progesterone receptor (PR)
tumor necrosis factor-
α
(TNF-
α
) proteins. Finally
UHPLC-LTQ-Orbitrap MS technology was used to detect the main chemical constituents of SJSJG
and the pharmacodynamic substance basis was analyzed based on the pharmacological effect.
Result
2
The results of animal experiments showed that compared with the normal group
nipple height and diameter of the model group increased remarkably (
P
<
0.01)
serum E
2
significantly increased (
P
<
0.01). Pathological examination showed abnormal hyperplasia of breast tissue, expressions of ER
α
AR
PR and TNF-
α
increased, compared with the model group
the nipple height and diameter of the SJSJG group decreased remarkably (
P
<
0.01)
serum E
2
was decreased significantly (
P
<
0.01), pathological examination showed weakened abnormal hyperplasia of breast tissue
ER
α
AR
PR and TNF-
α
protein expressions were significant decreased (
P
<
0.01). The results of basic material study showed that 85 chemical components were identified from SJSJG
including 16 alkaloids
7 flavonoids
15 terpenes
9 phenolic acid compounds
3 coumarin compounds
10 esters and lactone compounds
7 fatty acids compounds
4 amino acids compounds
and 14 other types of ingredients, among them
alkaloids and terpenoids chemical drug substances were closely related.
Conclusion
2
SJSJG can effectively improve the condition of breast hyperplasia
and its medicinal substance basis may include saikosaponin A
Saikosaponin D
verticinone
peimine.
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