西黄丸干预大鼠乳腺癌癌前病变的效果及机制研究  

Effect and mechanism of Xihuang Pills on rats with precancerous lesions of breast

作　　者：张咏佳 黄潘雯 张永太[1] 王志[1] 冯年平[1] ZHANG Yong-jia;HUANG Pan-wen;ZHANG Yong-tai;WANG Zhi;FENG Nian-ping(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学,上海201203

出　　处：《中国中药杂志》2023年第13期3546-3555,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81603308);上海高水平地方高校创新团队支持项目(SZY20220315);上海中医药大学预算内科研项目(2021LK106)。

摘　　要：研究西黄丸对乳腺癌癌前病变大鼠干预作用及机制。48只健康雌性大鼠随机选8只设为空白组,其余40只采用7,12-二甲基苯并蒽(DMBA)联合雌、孕激素建立乳腺癌癌前病变模型。将模型复制成功的大鼠随机分为模型组、他莫昔芬组(1.8 mg·kg^(-1)·d^(-1))以及西黄丸低(0.3 g·kg^(-1)·d^(-1))、中(0.6 g·kg^(-1)·d^(-1))、高(1.2 g·kg^(-1)·d^(-1))剂量组。给药30 d后,HE染色观察内脏、乳腺组织病理变化,计算脏器指数,ELISA法检测血清雌二醇(estradiol,E_(2))、孕酮(progesterone,P)含量,免疫组化法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)、碱性成纤维细胞生长因子2(fibroblast growth factor 2,FGF2)蛋白表达,Western blot法检测VEGF、血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)、磷酸化VEGFR2(p-VEGFR2)、B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、Bcl-2关联X蛋白(Bcl-2 associated X protein,Bax)蛋白表达,RT-PCR法检测VEGF、FGF2、CXC趋化因子受体4(CXC-chemokine receptor 4,CXCR4)、半胱氨酸天冬氨酸特异性蛋白酶3(cysteine aspastic acid-specific protease 3,caspase-3)、基质细胞衍生因子1(stromal cell-derived factor 1,SDF-1)mRNA表达。HE染色显示该模型对大鼠肝、肾有一定损伤,模型组乳腺组织重度增生,西黄丸高剂量组乳腺组织表现为轻度增生。与模型组相比,西黄丸组卵巢系数显著降低(P<0.05或P<0.01),高剂量组子宫系数显著降低(P<0.01)。ELISA结果表明,与模型组相比,西黄丸高剂量组E_(2)和P水平显著降低(P<0.05或P<0.01)。与模型组相比,西黄丸组大鼠VEGF、FGF2蛋白及mRNA表达水平明显降低(P<0.05或P<0.01),Bcl-2蛋白表达显著降低(P<0.01);西黄丸中、高剂量组VEGFR2、p-VEGFR2蛋白表达显著降低(P<0.01),CXCR4、SDF-1 mRNA表达显著降低(P<0.01),caspase-3 mRNA表达显著升高(P<0.01);西黄丸高剂量组Bax蛋白表达显著升高(P<0.01)。以上结果表明,西黄�The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast.Of 48 healthy female rats,8 were randomly selected as blank group,and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast.The successfully modeled rats were randomly divided into a model group,a tamoxifen group(1.8 mg·kg^(-1)·d^(-1)),a Xihuang Pills low-dose group(0.3 g·kg^(-1)·d^(-1)),a medium-dose group(0.6 g·kg^(-1)·d^(-1)) and a high-dose group(1.2 g·kg^(-1)·d^(-1)).After 30 days of admi-nistration,the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining,and the visceral index was calculated.Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum.The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry.The protein expressions of VEGF,vascular endothelial growth factor receptor 2(VEGFR2),phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2),B-cell lymphoma-2(Bcl-2),and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF,FGF2,CXC-chemokine receptor 4(CXCR4),cysteine aspartic acid-specific protease(caspase-3),and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR).HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue,while the Xihuang Pills high-dose group had mild hyperplasia.Compared with the model group,the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01).ELISA results showed that compared with the model group,expressions of E_(2) and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01).I

关 键 词：西黄丸 乳腺癌癌前病变 新生血管生成 

分 类 号：R285.5[医药卫生—中药学]