柴芍乳癖颗粒对乳腺增生模型大鼠血清激素水平和乳腺组织中VEGF和bFGF蛋白表达水平的影响及其意义
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摘要
目的:探讨柴芍乳癖颗粒对乳腺增生模型大鼠血清激素水平和乳腺组织中血管内皮生长因子(VEGF)和碱性成纤维细胞生成因子(bFGF)蛋白表达水平的影响,阐明其作用机制。方法:雌性SD大鼠60只随机分为对照组,模型组,他莫昔芬组(4 mg·kg~(-1)),低(0.45g·kg~(-1))、中(0.90g·kg~(-1))和高(1.80g·kg~(-1))剂量柴芍乳癖颗粒组;每组10只。对照组大鼠腹腔注射生理盐水0.05mL,常规喂养,其余各组大鼠均腹腔注射苯甲酸雌二醇0.5mg·kg~(-1),连续25d;然后除对照组外其他各组大鼠腹腔注射黄体酮注射液5mg·kg~(-1),连续5d,建立大鼠乳腺增生模型,连续给药8周。测量大鼠第2对乳头直径和高度。腹主动脉取血,酶联免疫吸附实验测定各组大鼠血清中雌二醇(E2)、孕酮(P)、黄体生成素(LH)、卵泡刺激素(FSH)、催乳素(PRL)、促性腺激素释放激素(GnRH)水平及VEGF和bFGF水平。免疫组织化学法检测各组大鼠乳腺组织中VEGF和bFGF蛋白表达水平。结果:与模型组比较,低、中和高剂量柴芍乳癖颗粒组大鼠乳腺腺泡形状规则,分泌物减少,细胞增生程度减轻。与模型组比较,低、中和高剂量柴芍乳癖颗粒组大鼠乳头高度和直径均明显降低(P<0.05),血清中E2、LH、PRL、GnRH、VEGF和bFGF水平均明显降低(P<0.05),同时血清P和FSH水平明显升高(P<0.05)。与模型组比较,低、中和高剂量柴芍乳癖颗粒组乳腺组织中VEGF和bFGF蛋白表达水平明显降低(P<0.05)。结论:柴芍乳癖颗粒对乳腺增生模型大鼠有明显的治疗作用,其机制可能是通过调节大鼠血清多种激素水平和乳腺组织中VEGF和bFGF蛋白表达水平达到治疗乳腺增生的目的。
Objective:To investigate the effects of Chaishao Rupi Granules on the levels of serum hormones and the expression levels of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)proteins in breast tissue of the model with mammary gland hyperplasia rats,and to clarify its therapeutic mechanism.Methods:Sixty female SD rats were selected and randomly divided into control group,model group,tamoxifen group(4 mg·kg~(-1)),and low(0.45 g·kg~(-1)),medium(0.90 g·kg~(-1))and high(1.80 g·kg~(-1))doses of Chaishao Rupi Granules groups.The rats in control group were intraperitoneally injected with normal saline(0.05 mL),and fed with normal diet;the rats in other groups were intraperitoneally injected with 0.5 mg·kg~(-1) estradiol benzoate for 25 d,then they were intraperitoneally injectcel with progesterone injection 5 mg·kg~(-1) for 5 d to establish the rat models of mammary gland hyperplasia,continuous administration for 8 weeks.The diameters and heights of the second nipples of the rats were measured,the blood of abdominal aorta was taken and the levels of estradiol(E2),progesterone(P),luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),gonadotropin-releasing hormone(GnRH)and the densities of VEGF and bFGF were detected with ELISA.Immunohistochemistry was used to detect the expressions of VEGF and bFGF in breast tissue of the rats in various groups.Results:Compared with model group,the acinar shapes in low,medium,and high doses of Chaishao Rupi Granules groups were regular,the secretion was reduced,and the degrees of cell proliferation were reduced.Compared with model group,the heights and diameters of nipples of the rats in low,medium,and high doses of Chaishao Rupi Granules groups were significantly decreased(P<0.05),the levels of E2,LH,PRL,GnRH,VEGF and bFGF in serum were significantly decreased(P<0.05),and the levels of serum P and FSH were significantly increased(P<0.05).Compared with model group,the expression levels of VRGF and bFGF in breast tissue of the rats in low,medium,and high doses of Chashao Rupi Granules groups were significantly decreased(P<0.05).Conclusion:Chaishao Rupi Granules have obvious therapeutic effect in the mammary hyperplasia model rats,and its mechanism is to regulate the serum levels of multiple hormones and the expression levels of VEGF and bFGF proteins in brease tissue of the rats to treat the mammary gland hyperplasia.
Objective:To investigate the effects of Chaishao Rupi Granules on the levels of serum hormones and the expression levels of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)proteins in breast tissue of the model with mammary gland hyperplasia rats,and to clarify its therapeutic mechanism.Methods:Sixty female SD rats were selected and randomly divided into control group,model group,tamoxifen group(4 mg·kg~(-1)),and low(0.45 g·kg~(-1)),medium(0.90 g·kg~(-1))and high(1.80 g·kg~(-1))doses of Chaishao Rupi Granules groups.The rats in control group were intraperitoneally injected with normal saline(0.05 mL),and fed with normal diet;the rats in other groups were intraperitoneally injected with 0.5 mg·kg~(-1) estradiol benzoate for 25 d,then they were intraperitoneally injectcel with progesterone injection 5 mg·kg~(-1) for 5 d to establish the rat models of mammary gland hyperplasia,continuous administration for 8 weeks.The diameters and heights of the second nipples of the rats were measured,the blood of abdominal aorta was taken and the levels of estradiol(E2),progesterone(P),luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),gonadotropin-releasing hormone(GnRH)and the densities of VEGF and bFGF were detected with ELISA.Immunohistochemistry was used to detect the expressions of VEGF and bFGF in breast tissue of the rats in various groups.Results:Compared with model group,the acinar shapes in low,medium,and high doses of Chaishao Rupi Granules groups were regular,the secretion was reduced,and the degrees of cell proliferation were reduced.Compared with model group,the heights and diameters of nipples of the rats in low,medium,and high doses of Chaishao Rupi Granules groups were significantly decreased(P<0.05),the levels of E2,LH,PRL,GnRH,VEGF and bFGF in serum were significantly decreased(P<0.05),and the levels of serum P and FSH were significantly increased(P<0.05).Compared with model group,the expression levels of VRGF and bFGF in breast tissue of the rats in low,medium,and high doses of Chashao Rupi Granules groups were significantly decreased(P<0.05).Conclusion:Chaishao Rupi Granules have obvious therapeutic effect in the mammary hyperplasia model rats,and its mechanism is to regulate the serum levels of multiple hormones and the expression levels of VEGF and bFGF proteins in brease tissue of the rats to treat the mammary gland hyperplasia.
引文
[1]马淑娟.浅谈乳腺增生的预防与治疗[J].世界最新医学,2016,16(50):176,179.
[2]赵文静,旺建伟,常惟智,等.仙鹿消癖胶囊对乳腺增生模型小鼠血管生成因子VEGF、bFGF、MVD表达的影响[J].上海中医药杂志,2014,48(3):74.
[3]胡彦武,任立群,Rita,等.复方鹿角乳痛宁胶囊对乳腺增生大鼠的改善作用及其机制研究[J].中国药房,2016,27(1):29-32.
[4]王月,刘丽芳.柴芍乳癖汤治疗乳腺增生病疗效观察[J].广西中医药,2012,1(2):14-15.
[5]杨春萍,刘丽芳,杨涛,等.柴芍乳癖颗粒对乳腺增生病兔模型乳腺组织B超声像及组织形态学的影响[J].湖南中医药大学学报,2016,36(9):29-32.
[6]史振滏,刘国莉,路艺.柴芍乳癖合剂治疗肝郁痰凝型乳腺增生症40例[J].中国民族民间医药,2017,26(5):105-106.
[7]李斌,廖秋月,王兆芬,等.中国女性乳腺增生危险因素Meta分析[J].中国健康教育,2016,32(5):443-446.
[8]刘齐,张立德,谷丽艳.针刺辨证治疗乳腺增生与雌激素水平关系理论探讨[J].辽宁中医药大学学报,2016,3(2):54-58.
[9]林妮,邱玉文,官娜.荔枝核皂苷对乳腺增生大鼠雌激素受体ERα、ERβ及ERK、VEGF表达的影响[J].中药材,2016,39(3):659-662.
[10]王苹,张婷婷,杨娜.当归芍药散加味对乳腺增生大鼠血液流变学及乳腺组织形态学的影响[J].福建中医药,2014,45(2):52-54.
[11]林娇燕.四肢阴经刮疗配合针刺对乳腺增生病患者微循环血流灌注量的影响[D].福州:福建中医药大学,2016.
[12]王琦,韩云志,尚立芝,等.柴胡疏肝散联合他莫昔芬对大鼠乳腺增生的干预作用[J].中医学报,2016,10(11):1734-1737.
[13]尚立芝,季书,王琦,等.柴胡疏肝散对肝郁性乳腺增生模型大鼠的保护作用[J].中国药房,2015,26(7):908-911.
[14]连小龙,韩涛.中药抗乳腺增生作用机制研究进展[J].中兽医医药杂志,2017,36(3):80-82.
[15]刘秀娟,王斌.雌激素与力竭运动对大鼠脑部VEGF、TGF-β1、eNOS表达的影响[J].南京体育学院学报:自然科学版,2015,8(4):1-6.
[16]谷丽艳,解静茹,刘齐,等.解毒胶囊对乳腺增生大鼠VEGF和bFGF表达的影响[J].中华中医药学刊,2016,5(7):1559-1562.
[17]刘齐.针刺对乳腺增生模型大鼠血管生成因子(VEGF、BFGF)影响的实验研究[D].沈阳:辽宁中医药大学,2016.
[18]赵文静,旺建伟,常惟智,等.仙鹿消癖胶囊对乳腺增生模型小鼠血管生成因子VEGF、bFGF、MVD表达的影响[J].上海中医药杂志,2014,3(2):74-78.
[19]靳亚慈.针药结合对实验性乳腺增生大鼠血管(VEGF、bFGF)生成的影响[D].石家庄:河北医科大学,2007.
[2]赵文静,旺建伟,常惟智,等.仙鹿消癖胶囊对乳腺增生模型小鼠血管生成因子VEGF、bFGF、MVD表达的影响[J].上海中医药杂志,2014,48(3):74.
[3]胡彦武,任立群,Rita,等.复方鹿角乳痛宁胶囊对乳腺增生大鼠的改善作用及其机制研究[J].中国药房,2016,27(1):29-32.
[4]王月,刘丽芳.柴芍乳癖汤治疗乳腺增生病疗效观察[J].广西中医药,2012,1(2):14-15.
[5]杨春萍,刘丽芳,杨涛,等.柴芍乳癖颗粒对乳腺增生病兔模型乳腺组织B超声像及组织形态学的影响[J].湖南中医药大学学报,2016,36(9):29-32.
[6]史振滏,刘国莉,路艺.柴芍乳癖合剂治疗肝郁痰凝型乳腺增生症40例[J].中国民族民间医药,2017,26(5):105-106.
[7]李斌,廖秋月,王兆芬,等.中国女性乳腺增生危险因素Meta分析[J].中国健康教育,2016,32(5):443-446.
[8]刘齐,张立德,谷丽艳.针刺辨证治疗乳腺增生与雌激素水平关系理论探讨[J].辽宁中医药大学学报,2016,3(2):54-58.
[9]林妮,邱玉文,官娜.荔枝核皂苷对乳腺增生大鼠雌激素受体ERα、ERβ及ERK、VEGF表达的影响[J].中药材,2016,39(3):659-662.
[10]王苹,张婷婷,杨娜.当归芍药散加味对乳腺增生大鼠血液流变学及乳腺组织形态学的影响[J].福建中医药,2014,45(2):52-54.
[11]林娇燕.四肢阴经刮疗配合针刺对乳腺增生病患者微循环血流灌注量的影响[D].福州:福建中医药大学,2016.
[12]王琦,韩云志,尚立芝,等.柴胡疏肝散联合他莫昔芬对大鼠乳腺增生的干预作用[J].中医学报,2016,10(11):1734-1737.
[13]尚立芝,季书,王琦,等.柴胡疏肝散对肝郁性乳腺增生模型大鼠的保护作用[J].中国药房,2015,26(7):908-911.
[14]连小龙,韩涛.中药抗乳腺增生作用机制研究进展[J].中兽医医药杂志,2017,36(3):80-82.
[15]刘秀娟,王斌.雌激素与力竭运动对大鼠脑部VEGF、TGF-β1、eNOS表达的影响[J].南京体育学院学报:自然科学版,2015,8(4):1-6.
[16]谷丽艳,解静茹,刘齐,等.解毒胶囊对乳腺增生大鼠VEGF和bFGF表达的影响[J].中华中医药学刊,2016,5(7):1559-1562.
[17]刘齐.针刺对乳腺增生模型大鼠血管生成因子(VEGF、BFGF)影响的实验研究[D].沈阳:辽宁中医药大学,2016.
[18]赵文静,旺建伟,常惟智,等.仙鹿消癖胶囊对乳腺增生模型小鼠血管生成因子VEGF、bFGF、MVD表达的影响[J].上海中医药杂志,2014,3(2):74-78.
[19]靳亚慈.针药结合对实验性乳腺增生大鼠血管(VEGF、bFGF)生成的影响[D].石家庄:河北医科大学,2007.