乳结消颗粒对肝郁气滞型乳腺增生模型大鼠的影响

Effects of Rujiexiao Keli on Rat Model of Mammary Glands Hyperplasia Combined with Liver Qi Stagnation Syndrome

目的观察乳结消颗粒对肝郁气滞型乳腺增生模型大鼠的药理作用及机制。方法采用慢性不可预知刺激+孤养复合前腋下注射苯甲酸雌二醇和黄体酮的方法,复制肝郁气滞证乳腺增生病大鼠模型。模型复制成功后,将大鼠随机分为7组(每组10只):正常对照组,模型组,乳结消颗粒大、中、小剂量组(12、6、3 g生药·kg^-1),乳疾灵颗粒组(8 g·kg^-1),三苯氧胺组(3.6 mg·kg^-1)。并按所述剂量灌胃给药,每日1次,连续给药30 d,正常对照组和模型组大鼠每日灌胃等体积蒸馏水(12 mL·kg^-1)。于模型复制前、模型复制30 d、给药15 d及给药30 d(实验结束),检测相关指标。结果乳结消颗粒明显减小模型大鼠乳头直径及乳腺体积(P <0.05,P <0.01),减轻乳腺质量(P <0.05,P <0.01),减少乳腺小叶数和小叶内腺泡数(P <0.05,P <0.01),减小腺泡腔直径和导管腔直径(P <0.05,P <0.01);显著降低血清雌二醇(E2)和催乳素(PRL)水平(P <0.05,P <0.01),升高血清超氧化物歧化酶(SOD)活性(P <0.05,P <0.01),减少血清丙二醛(MDA)含量(P <0.01);抑制子宫肿大和胸腺萎缩(P <0.05,P <0.01);显著降低雌激素受体(ER)、孕激素受体(PR)、细胞增殖核抗原(ki67)的表达(P <0.05,P <0.01);此外,明显改善模型大鼠外观体征、行为活动及情绪变化,促进体质量增长(P <0.05),明显提高模型大鼠蔗糖水偏嗜度(P <0.05,P <0.01),增加开野实验的活动次数(P <0.05,P <0.01)。上述作用以乳结消颗粒大、中剂量为显著。结论乳结消颗粒具有改善模型大鼠肝郁气滞状态,调节性激素水平,减轻乳房肿大,减轻乳腺组织增生性病变等作用;其作用机制可能与调节内分泌,增强清除氧自由基的能力,抑制脂质过氧化,降低ER、PR、ki67高表达水平等有关,这为该药在临床上的应用提供了实验依据。

Objective To observe the pharmacological effects and mechanism of Rujiexiao Keli on rat model of mammary glands hyperplasia combined with liver qi stagnation syndrome. Methods Chronic unpredictable stress and isolation together with hypodermic injection of estradiol benzoate and progestin in axilla were used on female rats to establish the rat model of mammary glands hyperplasia combined with liver qi stagnation syndrome. After modeling,rats were randomly divided into 7 groups(10 per group):normal control group,model group,high-dose,mediumdose and low-dose of Rujiexiao Keli groups(12,6,and 3 g crude drug·kg^-1,respectively)Rujiling Keli group(8 g · kg^-1),and tamoxifen group(3.6 mg·kg^-1). According to the dosage above,intragastric administration was conducted once a day for 30 days,while rats in normal control group and model group were given distilled water(12 mL·kg^-1). Measurements were conducted before modeling, 30 days after modeling, 15 days and 30 days after treatment. Results The papilla diameter, mammary gland volume, and mammary gland weight were significantly reduced in the Rujiexiao Keli groups(P < 0.05, P < 0.01). The number of mammary gland lobules, number of acinar glands in lobules,diameter of acinar gland cavities,and diameter of acinar gland ducts were also reduced in the Rujiexiao Keli groups(P < 0.05,P < 0.01). The serum estradiol(E2),prolactin(PRL)levels(P < 0.05,P <0.01)and the MDA concentrations(P < 0.01)were reduced,while serum SOD activities were significantly increased in the Rujiexiao Keli groups(P < 0.05,P < 0.01). The effect against uterus swelling and thymus atrophy(P < 0.05,P < 0.01),and a reduce of the expressions of ER,PR and ki67 were observed in Rujiexiao Keli groups(P < 0.05,P < 0.01). Additionally, the appearance, behavior, emotion, as well as the body weights(P < 0.05), syrup consumption(P < 0.05,P < 0.01)and behavior scores in the open field test(P < 0.05,P < 0.01)were promoted in Rujiexiao Keli groups. High and medium doses of Rujiexiao Keli had more significant effects. Conclusion Rujiexiao Keli has effects of relieving symptoms of liver qi stagnation, regulating gonadal hormone level, reducing breast swelling and hyperplasia in mammary glands,etc. The mechanism is likely related to endocrine system regulation,oxygen free radicals elimination, lipid peroxidation suppression and ER, PR and ki67 expression reduction. The current study provides experimental evidence for its clinical application.