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.
Abstract
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 uterine 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 the expression of ERα,PR and p-ERK1/2 proteins in rats.
基金项目
四川省中医药局中医药科研专项(2021MS485)