乳宁颗粒对乳腺增生伴乳痛患者内分泌激素和血管生成因子的影响
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摘要
目的:观察乳宁颗粒治疗肝郁痰凝型乳腺增生伴乳痛患者的疗效,探讨其对患者孕酮(P),雌二醇(E2),催乳素(PRL),黄体生成素(LH),卵泡刺激素(FSH)水平及血管生成因子血管生成素-2(Ang-2),缺氧诱导因子-1α(HIF-1α),血管内皮细胞生长因子(VEGF)和碱性成纤维细胞生长因子(b FGF)水平的影响。方法:选则女性乳腺增生症患者122例,随机按数字表法分为治疗组和对照组各61例。两组患者均口服逍遥丸,3次/d,8丸/次。对照组口服枸橼酸他莫昔芬片,20 mg/次,2次/d。治疗组在对照组治疗的基础上服用乳宁颗粒,1袋/次,3次/d。两组患者均连续观察8周。比较两组患者乳腺增生症状评分,Mc Gill疼痛问卷表(SF-MPQ)疼痛评分、肝郁痰凝证症状评分及临床疗效比较。检测两组血清内分泌激素P,E2,PRL,LH,FSH水平及Ang-2,HIF-1α,VEGF和b FGF水平。结果:治疗后,治疗组患者乳房肿块硬度、乳腺肿块大小评分及视觉模拟量表评分(VAS),现有疼痛强度(PPI),疼痛分级指数(PRI)评分均明显低于对照组(P<0.01);治疗后,治疗组患者肝郁痰凝证症状(善郁易怒、胸闷胁胀、失眠多梦、心烦口苦)评分均明显低于对照组(P<0.01);治疗组患者的临床总有效率为98.31%,明显高于对照组86.89%(χ2=4.319,P<0.05);治疗组治疗后血清内分泌激素E2,PRL和LH水平均明显低于对照组,P和FSH水平均明显高于对照组(P<0.01);治疗后,治疗组患者的血清血管生成因子Ang-2,HIF-1α,VEGF和b FGF水平均明显低于对照组(P<0.01)。结论:治疗组在对照组治疗的基础上,加服乳宁颗粒,对治疗肝郁痰凝型乳腺增生伴乳痛均有明显疗效,调节患者体内的内分泌激素(P,E2,PRL,LH,FSH水平)和血管生成因子(Ang-2,HIF-1α,VEGF和b FGF)水平可能与其疗效有关。
Objective: To observe the efficacy of Runing granule in treating hyperplasia of mammary glands with syndrome of liver qi depression and phlegm stasis,and investigate its effects on progesterone(P),estradiol(E2),prolactin(PRL),luteinizing hormone(LH),follicle stimulating hormone(FSH) and angiogenic factors angiopoietin(Ang)-2,hypoxia inducible factor(HIF)-1α,vascular endothelial growth factor(VEGF),and basic fibroblast growth factor(b FGF). Method: One hundred and twenty-two female patients with hyperplasia of mammary glands were selected and randomly divided into treatment group and control group with 61 cases in each group according to random number table. Both groups were orally with Xiaoyao wan(8 pills/time and tid). The patients in control group were additionally treated with Tamoxifen citrate tablets(20 mg/time and bid). Based on the treatment in control group,the patients in treatment group were additionally treated with Runing granule(1 bag/time and tid). Both groups were treated for 8 weeks. Scores of mammary gland hyperplasia symptoms,simple Mc Gill pain questionnaire(SF-MPQ),and symptoms of syndrome of liver Qi depression and phlegm stasis and efficacy were compared between two groups. Serum levels of P,E2,PRL,LH,and FSH as well as Ang-2,HIF-1α,VEGF,and b FGF were detected in both groups. Result: After treatment,scores of hyperplasia of mammary glands for breast lump hardness and gland tumor size,as well as SF-MPQ scale visual analogue scale(VAS),present pain intensity(PPI),pain rating index(PRI) of treatment group were evidently lower than those in control group(P < 0. 01). After treatment,scores of symptoms of syndrome of liver qi depression and phlegm stasis(depression and irritability,chest distress,insomnia and dreamy sleep,upset and bitter mouth) of treatment group were evidently lower than those of control group(P < 0. 01). Total clinical effective rate of treatment group was 98. 31%,obviously higher than 86. 89% in control group(χ2= 4. 319,P < 0. 05). After treatment,serum levels of E2,PRL,and LH in treatment group were remarkably lower,while P and FSH level were obviously higher than those in control group(P < 0. 01). After treatment,serum levels of ngiogenic factors Ang-2,HIF-1α,VEGF,and b FGF in treatment group were obviously lower than those in control group(P < 0. 01). Conclusion: Based on routine therapy,the efficacy of additional Runing Granule in treating hyperplasia of mammary glands with syndrome of liver qi depression and phlegm stasis is significant,which may be correlated with regulation of endocrine hormones(P,E2,PRL,LH,and FSH) and angiogenic factors(Ang-2,HIF-1α,VEGF,and b FGF).
Objective: To observe the efficacy of Runing granule in treating hyperplasia of mammary glands with syndrome of liver qi depression and phlegm stasis,and investigate its effects on progesterone(P),estradiol(E2),prolactin(PRL),luteinizing hormone(LH),follicle stimulating hormone(FSH) and angiogenic factors angiopoietin(Ang)-2,hypoxia inducible factor(HIF)-1α,vascular endothelial growth factor(VEGF),and basic fibroblast growth factor(b FGF). Method: One hundred and twenty-two female patients with hyperplasia of mammary glands were selected and randomly divided into treatment group and control group with 61 cases in each group according to random number table. Both groups were orally with Xiaoyao wan(8 pills/time and tid). The patients in control group were additionally treated with Tamoxifen citrate tablets(20 mg/time and bid). Based on the treatment in control group,the patients in treatment group were additionally treated with Runing granule(1 bag/time and tid). Both groups were treated for 8 weeks. Scores of mammary gland hyperplasia symptoms,simple Mc Gill pain questionnaire(SF-MPQ),and symptoms of syndrome of liver Qi depression and phlegm stasis and efficacy were compared between two groups. Serum levels of P,E2,PRL,LH,and FSH as well as Ang-2,HIF-1α,VEGF,and b FGF were detected in both groups. Result: After treatment,scores of hyperplasia of mammary glands for breast lump hardness and gland tumor size,as well as SF-MPQ scale visual analogue scale(VAS),present pain intensity(PPI),pain rating index(PRI) of treatment group were evidently lower than those in control group(P < 0. 01). After treatment,scores of symptoms of syndrome of liver qi depression and phlegm stasis(depression and irritability,chest distress,insomnia and dreamy sleep,upset and bitter mouth) of treatment group were evidently lower than those of control group(P < 0. 01). Total clinical effective rate of treatment group was 98. 31%,obviously higher than 86. 89% in control group(χ2= 4. 319,P < 0. 05). After treatment,serum levels of E2,PRL,and LH in treatment group were remarkably lower,while P and FSH level were obviously higher than those in control group(P < 0. 01). After treatment,serum levels of ngiogenic factors Ang-2,HIF-1α,VEGF,and b FGF in treatment group were obviously lower than those in control group(P < 0. 01). Conclusion: Based on routine therapy,the efficacy of additional Runing Granule in treating hyperplasia of mammary glands with syndrome of liver qi depression and phlegm stasis is significant,which may be correlated with regulation of endocrine hormones(P,E2,PRL,LH,and FSH) and angiogenic factors(Ang-2,HIF-1α,VEGF,and b FGF).
引文
[1]吴阶平,裘法祖.黄家驷外科学[M].5版.北京:人民卫生出版社,1996:82-83.
[2]王中元,康斐,王红玲.疏肝消癥方治疗乳腺增生症65例[J].河南中医,2017,37(8):1412-1414.
[3]胡彦武,任立群,RITA,等.复方鹿角乳痛宁胶囊抗乳腺增生和镇痛的作用[J].中国实验方剂学杂志,2016,22(20):122-126.
[4]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.
[5]陈焕龄.乳宁颗粒治疗乳腺增生症400例临床观察[J].临床医药文献杂志,2017,4(73):14429-14430.
[6]姚乐申.乳宁颗粒治疗220例乳腺增生临床病例疗效观察[J].实用妇科内分泌杂志,2017,4(15):13-15.
[7]GAO Z,ZHANG G,YU J,et al.Superovulation does not affect the endocrine activity nor increase susceptibility to carcinogenesis of uterine and mammary glands of female off spring in mice[J].J Assist Reprod Genet,2014,31(9):1243-1249.
[8]李睿,孔艳,刘增辉,等.乳复宁颗粒调节乳腺增生症家兔激素水平以及VEGF蛋白表达变化的研究[J].中国临床药理学与治疗学,2018,23(2):138-142.
[9]中华预防医学会妇女保健分会乳腺保健与乳腺疾病防治学组.乳腺增生症诊治专家共识[J].中国实用外科杂志,2016,36(7):759-762.
[10]李曰庆.中医外科学[M].2版.北京:中国中医药出版社,2008:83.
[11]国家中医药管理局.24个专业104个病种中医诊疗方案·乳癖中医诊疗方案[M].北京:国家中医药管理局医政司,2011:260-261.
[12]李君,冯艺,韩济生,等.中文版简版Mc Gill疼痛问卷-2的制定与多中心验证[J].中国疼痛医学杂志,2013,19(1):42-46.
[13]国家中医药管理局.中医病证诊断疗效标准[M].南京:南京大学出版社,1994:131-132.
[14]吴雪卿,唐汉钧.唐汉钧从肝、脾、肾-冲任治疗乳腺增生症[J].山东中医杂志,2017,36(3):221-223.
[15]LIN N,QIU Y W,HE G Y,et al.Effects of litchi chinensis seed saponins on inhibiting hyperplasia of mammary glands and influence on signaling pathway of estrogen in rats[J].J Chin Med Mater,2015,38(4):798-802.
[16]才旦多杰,赵海宁,施志军.桂枝茯苓丸辅助治疗乳腺增生的疗效及安全性观察[J].山东医药,2016,56(34):68-70.
[17]方芳,郭汝松,刘云涛,等.期门穴刺络拔罐治疗乳腺增生的效果[J].广东医学,2016,37(12):1881-1883.
[18]沈爱玲,丁优,罗小光.通络刮痧法对肝郁血瘀型乳腺增生大鼠乳房微循环及血管生成的影响[J].中华中医药杂志,2015,30(7):2521-2524.
[19]Rahbari-Oskoui F F,Chapman A B.Hypoxia-Inducible factor-1α(HIF-1α),angiopoietin-2(ANG-2)and endocan:novel biomarkers of disease progression involving polycystic kidney disease[J].Am J Nephrol,2018,47(4):228-230.
[20]Biel N M,Siemann D W.Targeting the angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference[J].Cancer Lett,2016,380(2):525-533.
[21]Baker L C J,Boult J K R,Thomas M,et al.Acute tumour response to a bispecific Ang-2-VEGF-A antibody:insights from multiparametric MRI and gene expression profiling[J].Br J Cancer,2016,115(6):691-702.
[22]杨琳红,张爱华,范宗宪,等.HIF-1α基因干扰对低氧环境下人鼻黏膜上皮细胞TGF-β1,VEGF,b FGF表达的影响及其机制[J].山东医药,2017,57(44):42-45.
[23]CHEN J,FU Y,DAY D S,et al.VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis[J].Nat Commun,2017,8(1):383.
[24]谷丽艳,解静茹,刘齐,等.解毒胶囊对乳腺增生大鼠VEGF和b FGF表达的影响[J].中华中医药学刊,2016,34(7):1559-1562.
[2]王中元,康斐,王红玲.疏肝消癥方治疗乳腺增生症65例[J].河南中医,2017,37(8):1412-1414.
[3]胡彦武,任立群,RITA,等.复方鹿角乳痛宁胶囊抗乳腺增生和镇痛的作用[J].中国实验方剂学杂志,2016,22(20):122-126.
[4]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.
[5]陈焕龄.乳宁颗粒治疗乳腺增生症400例临床观察[J].临床医药文献杂志,2017,4(73):14429-14430.
[6]姚乐申.乳宁颗粒治疗220例乳腺增生临床病例疗效观察[J].实用妇科内分泌杂志,2017,4(15):13-15.
[7]GAO Z,ZHANG G,YU J,et al.Superovulation does not affect the endocrine activity nor increase susceptibility to carcinogenesis of uterine and mammary glands of female off spring in mice[J].J Assist Reprod Genet,2014,31(9):1243-1249.
[8]李睿,孔艳,刘增辉,等.乳复宁颗粒调节乳腺增生症家兔激素水平以及VEGF蛋白表达变化的研究[J].中国临床药理学与治疗学,2018,23(2):138-142.
[9]中华预防医学会妇女保健分会乳腺保健与乳腺疾病防治学组.乳腺增生症诊治专家共识[J].中国实用外科杂志,2016,36(7):759-762.
[10]李曰庆.中医外科学[M].2版.北京:中国中医药出版社,2008:83.
[11]国家中医药管理局.24个专业104个病种中医诊疗方案·乳癖中医诊疗方案[M].北京:国家中医药管理局医政司,2011:260-261.
[12]李君,冯艺,韩济生,等.中文版简版Mc Gill疼痛问卷-2的制定与多中心验证[J].中国疼痛医学杂志,2013,19(1):42-46.
[13]国家中医药管理局.中医病证诊断疗效标准[M].南京:南京大学出版社,1994:131-132.
[14]吴雪卿,唐汉钧.唐汉钧从肝、脾、肾-冲任治疗乳腺增生症[J].山东中医杂志,2017,36(3):221-223.
[15]LIN N,QIU Y W,HE G Y,et al.Effects of litchi chinensis seed saponins on inhibiting hyperplasia of mammary glands and influence on signaling pathway of estrogen in rats[J].J Chin Med Mater,2015,38(4):798-802.
[16]才旦多杰,赵海宁,施志军.桂枝茯苓丸辅助治疗乳腺增生的疗效及安全性观察[J].山东医药,2016,56(34):68-70.
[17]方芳,郭汝松,刘云涛,等.期门穴刺络拔罐治疗乳腺增生的效果[J].广东医学,2016,37(12):1881-1883.
[18]沈爱玲,丁优,罗小光.通络刮痧法对肝郁血瘀型乳腺增生大鼠乳房微循环及血管生成的影响[J].中华中医药杂志,2015,30(7):2521-2524.
[19]Rahbari-Oskoui F F,Chapman A B.Hypoxia-Inducible factor-1α(HIF-1α),angiopoietin-2(ANG-2)and endocan:novel biomarkers of disease progression involving polycystic kidney disease[J].Am J Nephrol,2018,47(4):228-230.
[20]Biel N M,Siemann D W.Targeting the angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference[J].Cancer Lett,2016,380(2):525-533.
[21]Baker L C J,Boult J K R,Thomas M,et al.Acute tumour response to a bispecific Ang-2-VEGF-A antibody:insights from multiparametric MRI and gene expression profiling[J].Br J Cancer,2016,115(6):691-702.
[22]杨琳红,张爱华,范宗宪,等.HIF-1α基因干扰对低氧环境下人鼻黏膜上皮细胞TGF-β1,VEGF,b FGF表达的影响及其机制[J].山东医药,2017,57(44):42-45.
[23]CHEN J,FU Y,DAY D S,et al.VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis[J].Nat Commun,2017,8(1):383.
[24]谷丽艳,解静茹,刘齐,等.解毒胶囊对乳腺增生大鼠VEGF和b FGF表达的影响[J].中华中医药学刊,2016,34(7):1559-1562.