双金散结颗粒治疗乳腺增生的药效及物质基础  

Efficacy and Material Basis of Shuangjin Sanjie Granules in Treatment on Hyperplasia of Mammary Gland

作　　者：毕于聪 史渊源 张林[1,2] 范春兰 李佳林 任冬玲 徐砚通 王春国[1] 王停[1,2] BI Yu-cong;SHI Yuan-yuan;ZHANG Lin;FAN Chun-lan;LI Jia-lin;REN Dong-ling;XU Yan-tong;WANG Chun-guo;WANG Ting(Beijing University of Chinese Medicine,Beijing 100029,China;Key Laboratory of Famous Doctors and Famous Prescriptions Under State Administration of Traditional Chinese Medicine,Beijing 100029,China)

机构地区：[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

出　　处：《中国实验方剂学杂志》2020年第13期111-117,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家“重大新药创制”科技重大专项(2017ZX09301011)。

摘　　要：目的: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: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(E2),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(ERα),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: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E2显著升高(P<0.01);病理学检测表明乳腺组织异常增生;ERα,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E2显著下降(P<0.01);病理学检测表明乳腺组织异常增生减弱;ERα,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: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: The SD rat model of hyperplasia of mammary gland(HMG)and the ultrahighperformance 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: SD rat models of HMG were administered in groups,and the nipple height and the diameter were measured;the levels of estradiol(E2),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(ERα),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: 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 E2 significantly increased(P<0. 01). Pathological examination showed abnormal hyperplasia of breast tissue,expressions of ERα,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 E2 was decreased significantly(P<0. 01),pathological examination showed weakened abnormal hyperplasia of breast tissue,ERα,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: SJSJG can effectively improve the condition of breast hyperplasia,and its medicinal

关 键 词：双金散结颗粒 乳腺增生 药效 物质基础 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]