橙皮苷对雌激素和孕激素诱导雌性大鼠乳腺增生的抑制作用  

Inhibitory effects of hesperidin on estrogen-and progestin-induced mammary hyperplasia in female rats

作　　者：杨阳 杨晓芬 黄培森 冷婕 杨凡 李永佳[3] YANG Yang;YANG Xiao-fen;HUANG Pei-Sen;LENG Jie;YANG Fan;LI Yong-Jia(School of Acupuncture and Rehabilitation,Dazhou Vocational College of Traditional Chinese Medicine,Dazhou 635000,Sichuan Province,China;Department of Intensive Care Medicine,Dazhou Central Hospital,Dazhou 635000,Sichuan Province,China;Department of Traditional Chinese Medicine,Dazhou Central Hospital,Dazhou 635000,Sichuan Province,China;Department of Development Planning,Sichuan University of Arts and Sciences,Dazhou 635000,Sichuan Province,China;Department of Breast Thyroid Vascular Surgery,Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Gynecology,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,Sichuan Province,China)

机构地区：[1]达州中医药职业学院针灸康复学院,四川达州635000 [2]达州市中心医院重症医学科,四川达州635000 [3]达州市中心医院中医科,四川达州635000 [4]四川文理学院发展规划处,四川达州635000 [5]西南医科大学附属中医医院乳腺甲状腺血管外科,四川泸州646000 [6]川北医学院附属医院妇科,四川南充637000

出　　处：《中国临床药理学杂志》2024年第1期77-81,共5页The Chinese Journal of Clinical Pharmacology

基　　金：四川省中医药管理局中医药科研专项基金资助项目(2021MS485)。

摘　　要：目的研究橙皮苷(Hsp)对乳腺增生(MGH)大鼠的治疗作用,及可能的作用机制。方法将60只雌性大鼠随机分为空白组、模型组、对照组和低、中、高剂量实验组,每组10只。除空白组外,其余各组均肌内注射雌激素和孕激素诱导大鼠MGH模型。低、中、高剂量实验组分别灌胃给予25、50、100 mg·kg^(-1)的Hsp;对照组灌胃给予5 mg·kg^(-1)的他莫昔芬;空白组和模型组均灌胃给予等体积0.9%NaCl。6组大鼠每天给药1次,持续给药30 d。给药结束后,测量大鼠乳头高度和直径及子宫系数,用酶联免疫吸附试验法检测血清性激素含量,用试剂盒检测氧化应激指标的水平,用蛋白质印迹法检测相关蛋白的表达水平。结果中、高剂量实验组和对照组、模型组、空白组大鼠的乳头直径分别为(1.41±0.20)、(1.18±0.21)、(1.23±0.20)、(1.75±0.13)和(1.02±0.06)mm,乳头高度分别为(1.62±0.24)、(1.41±0.19)、(1.47±0.16)、(1.87±0.32)和(1.23±0.14)mm,子宫系数分别为(0.55±0.08)、(0.37±0.05)、(0.41±0.04)、(0.72±0.11)和(0.34±0.03)mg·g^(-1),雌激素受体α(ERα)相对表达水平分别为0.54±0.05、0.13±0.02、0.13±0.03、0.89±0.08和0.10±0.02,孕酮受体(PR)相对表达水平分别为0.43±0.03、0.08±0.01、0.87±0.07、0.20±0.04和0.14±0.03,磷酸化细胞外调节激酶1/2(ERK1/2)/ERK1/2分别为0.50±0.03、0.06±0.02、0.83±0.05、0.09±0.04和0.04±0.01。中、高剂量实验组和对照组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论Hsp可减少大鼠乳头直径、高度及子宫系数,调节性激素水平,抗氧化应激,抑制ERα、PR和p-ERK1/2蛋白表达。Objective To investigate the therapeutic effect of hesperidin(Hsp)on mammary gland hyperplasia(MGH)rats and the possible mechanism.Methods Sixty female rats were randomly divided into blank,model,control and experimental-L,-M,-H groups.Except for blank group,all other groups were injected intramuscularly with estrogen and progestin to induce MGH model in rats.The experimental-L,-M and-H groups were given 25,50,100 mg·kg^(-1)Hsp by gavage.The control group was given 5 mg·kg^(-1)tamoxifen by gavage.The blank and control groups were given an equal volume of 0.9%NaCl by gavage.Six groups of rats were administered once a day for 30 days.After the administration,the height and diameter of nipples and the ute rin e coefficient were measured.The serum sex hormone content was detected using enzyme-linked immunosorbent assay,the levels of oxidative stress indicators were detected using corresponding kits,and the expressions of related proteins were detected using Western blot.Results The nipple diameters of rats in experimental-M and-H groups,control group,model group and blank group were(1.41±0.20),(1.18±0.21),(1.23±0.20),(1.75±0.13)and(1.02±0.06)mm;the nipple heights were(1.62±0.24),(1.41±0.19),(1.47±0.16),(1.87±0.32)and(1.23±0.14)mm;the uterine indexes were(0.55±0.08),(0.37±0.05),(0.41±0.04),(0.72±0.11)and(0.34±0.03)mg·g^(-1);the relative expression levels of estrogen receptor alpha(ERα)were 0.54±0.05,0.13±0.02,0.13±0.03,0.89±0.08 and 0.10±0.02;the relative expression levels of progesterone receptor(PR)were 0.43±0.03,0.08±0.01,0.87±0.07,0.20±0.04 and 0.14±0.03;the phosphorylated-extracellular-regulated kinase 1/2(ERK1/2)/ERK1/2 were 0.50±0.03,0.06±0.02,0.83±0.05,0.09±0.04 and 0.04±0.01,respectively.Compared with model group,the differences of above indexes in the experimental-M,-H groups and control group were statistically significant(all P<0.05).Conclusion Hsp could reduce nipple diameter,height,and uterine coefficient,regulate sex hormone levels,resist oxidative stress,and inhibit th

关 键 词：橙皮苷 雌激素 乳腺增生 超氧化物歧化酶 细胞外调节激酶1/2 

分 类 号：R28[医药卫生—中药学]