【作者】 陈景伟；

【导师】 杜惠兰；

【作者基本信息】 河北医科大学 ， 中西医结合临床， 2007， 硕士

【摘要】 目的:子宫内膜异位症是指有活力的子宫内膜组织(腺体和间质)生长在子宫腔以外的部位,是妇科常见病和多发病,临床多以痛经、不孕、盆腔痛为主症。近年的研究发现此病的发生与血管形成密切相关,已成为国内外妇产科医生关注的热点。本研究通过分析VEGF、HIF-1α、MVD、ER、PR在内异症在位内膜、异位内膜的表达以及VEGF、E2、P、CA125在内异症血清和腹腔液中的含量,以期阐明内异症的部分发病机制;并对内异症患者运用补肾温阳化瘀法进行治疗,分析治疗前后各项指标变化,以探讨补肾温阳化瘀法治疗子宫内膜异位症的疗效及作用机理,为子宫内膜异位症的治疗提供新的思路。方法:选自2005年10月～2006年12月在石家庄市四院就诊,符合内异症诊断标准、纳入标准、排除标准及中医辨证标准的内异症患者60例,随机分为两组,中药组、西药组各30例,中药组连续服用补肾温阳化瘀中药3个月经周期,西药组连续服用孕三烯酮3个月经周期,观察期间不得服用与本病症有关的其他中西医药物,治疗前后于卵泡期相同时间分别抽取空腹肘静脉血;对照组来自无心、脑、肝、肾、血液病及内分泌疾病的自愿受试者30名,于卵泡期采血;收集因内异症或子宫肌瘤收入病房的患者60例,其中内异症患者30例,称为内异症组,子宫肌瘤患者30例,称为对照组,分别于手术过程中收集腹腔液、在位内膜、异位内膜、正常内膜组织,术后病理证实为内异症或正常子宫内膜。采用免疫组织化学SP法测定VEGF、HIF-1α、ER、PR、MVD在内异症在位、异位内膜中的表达,比较其表达强度。采用放射免疫法及酶联免疫法测定VEGF、CA125、E2、P在血清及腹腔液中的含量。全部患者均知情同意,并除外心脑肝肾疾病,治疗前3个月无激素类药物治疗史,各组年龄比较分布均衡,无统计学差异,具有可比性。结果:1内异症内膜组织中VEGF、HIF-1α、MVD、ER、PR的表达1.1内异症内膜组织中VEGF的表达VEGF在内异症在位、异位内膜的表达明显高于对照组内膜(均为P<0.01),在位内膜与异位内膜之间,无明显差异(P>0.05)。1.2内异症内膜组织中HIF-1α的表达HIF-1α在内异症在位、异位内膜的表达明显高于对照组内膜(均为P<0.01),在位内膜与异位内膜之间无明显差异(P>0.05)。1.3内异症内膜组织中MVD的表达MVD在内异症在位、异位内膜的表达明显高于对照组(均为P<0.01),在位内膜与异位内膜之间,无明显差异(P>0.05)。1.4内异症内膜组织中ER、PR的表达ER、PR在异位内膜的表达低于对照组内膜(均为P<0.01),在位内膜与对照组内膜之间无明显差异(均为P>0.05),ER、PR在异位内膜的表达低于在位内膜(均为P<0.01)。1.5内异症内膜组织中VEGF、HIF-1α、MVD表达的相关性内异症在位内膜、异位内膜中MVD与VEGF的表达呈正相关关系(r=0.510,r=0.673,P<0.05,P<0.01),MVD与HIF-1α的表达呈正相关关系(r=0.559,r=0.435,P<0.01,P<0.05),HIF-1α与VEGF的表达亦呈正相关关系(r=0.492,r=0.695,P<0.05,P<0.01)。2内异症腹腔液中E2、P、VEGF、CA125的含量内异症腹腔液中E2含量显著高于对照组,有统计学意义(P<0.05),P含量显著低于对照组,有统计学意义(P<0.01),VEGF含量显著高于对照组,有统计学意义(P<0.05)。CA125含量显著高于对照组,有统计学意义(P<0.05)。3补肾温阳化瘀法疗效观察及治疗前后血清中E2、P、VEGF、CA125含量的变化3.1补肾温阳化瘀法疗效观察子宫内膜异位症患者(30例),经补肾温阳化瘀法治疗后,临床治愈7例(23.33%),显效9例(30.00%),有效6例(20.00%),无效8例(26.67%),总有效22例,总有效率为73.33%。3.2治疗前后血清中E2、P、VEGF、CA125含量的变化经补肾温阳化瘀法治疗后,E2含量显著下降,与治疗前相比有明显差异(P<0.01),与对照组相比无明显差异(P>0.05)。P含量显著升高,与治疗前相比有明显差异(P<0.01),与对照组相比无明显差异(P>0.05)。VEGF含量显著下降,与治疗前相比有明显差异(P<0.01),与对照组相比无明显差异(P>0.05)。CA125含量显著下降,与治疗前相比有明显差异(P<0.01),与对照组相比仍有明显差异(P<0.01)。结论:本研究显示VEGF、HIF-1α、ER、PR均表达于在位及异位子宫内膜中,内异症患者在位及异位内膜中VEGF、HIF-1α的过度表达可能在内异症病灶形成中起重要作用。VEGF与HIF-1α在促进异位病灶血管形成过程中具有协同作用,从而表明VEGF与HIF-1α的促血管生成是内异症发生和发展过程中的一个重要环节。内异症血清及腹腔液中VEGF、E2、P、CA125含量均显著区别于对照组,提示内异症的发生与血管生成因子及性激素有密切的关系。补肾温阳化瘀中药可以降低内异症患者升高的VEGF、E2、CA125水平,升高P水平。提示补肾温阳化瘀法可通过调节患者的激素水平、降低血管生成因子水平起到治愈内异症的作用。更多还原

【Abstract】 Objective:Endometriosis(EM)is a common disease defined as the growth of endometrial tissue(glands and stroma) outside the uterine cavity that often results in a vast array of gynecological problems including dysmenorrhe,pelvic pain and infertility.EM is a commonly and frequently encountered gynecological disease. Recently,much attention has been focused on the role of angiogenic factors on the pathogenesis of endometriosis. The aim of this experiment is to investigate the expression of VEGF、HIF-1α、MVD、ER、PR in EM and the content of VEGF、E2、P、CA125 in serum and peritoneal fluid , in order to reveal the relationships between angiogenesis and EM, also we analyzed the changes of pretreatment and post-treatment by tonifying kidney warming yang removing blood stasis method in order to disproof the relationship between angiogenesis and EM. Also we hope to provide new method for the treatment of EM.Methods:Sixty patients who fitted the diagnostic standard, included standard, excluded standard and traditional Chinese medicine standard in differentiation of symptoms and signs of EM coming from the fourth hospital of city Shijiazhuang during October 2005 to Decemberr 2006 were collected.Thirty cases were treated by the tonifying kidney warming yang removing blood stasis method for three menstrual cycles.The other thirty cases were treated by Gestrinone.During the observed course,the patients did not take any other herb or western drug.we collected blood from ulnar vein in pretherapy and posttherapy during the same time of the menstrual cycle(the day 5～10). 30 voluntary subjects were selected as serum control group eliminating disease in heart, kidney or endocrine system etc.We collect 30 cases with endometriosis called EM group ,and 30 cases with myoma of uterus called control group, peritoneal fluid、eutopic endometrium、ectopic endometrium and normal endometrium were collected while operating, diagnosis was confirmed by pathological examination. Immuno-histochemical staining was used to detect VEGF、HIF-1α、MVD、ER、PR expression in different parts of the uterus,detected the contents of VEGF、E2、P、CA125 in serum and peritoneal fluid by means of radio immunoassay or enzyme linked immunosorbent assay. Since the control group cases had no significant difference with the patients in age, they were comparable.Result:1 The expression of VEGF、HIF-1α、MVD、ER、PR in endometriosis1.1 Expression of VEGF in endometriosis Compared with control group, the expression of VEGF in eutopic and ectopic endometrium significantly increased (all P<0.01), there was no statistical differences between eutopic endometrium and ectopic endometrium(P>0.05).1.2 Expression of HIF-1αin endometriosisCompared with control group, the expression of HIF-1αin eutopic and ectopic endometrium significantly increased(all P< 0.01),there was no statistical differences between eutopic endometrium and ectopic endometrium(P>0.05).1.3 Expression of MVD in endometriosisCompared with control group, the expression of MVD in eutopic and ectopic endometrium significantly increased(all P<0.01),there was no statistical differences between eutopic endometrium and ectopic endometrium(P>0.05).1.4 Expression of ER、PR in endometriosisThe expression of ER and PR in ectopic endometrium was significantly lower than that of control endometrium(all P<0.01),there was no significant differences between eutopic endometrium and control endometrium(all P>0.05).The expre- ssion of ER and PR in ectopic endometrium was lower than that in eutopic endometrium(all P<0.01),compared to the control endometrium,there was no significant differences. 1.5 The correlation among VEGF、HIF-1αand MVD in endometriosisThe study result indicated that there was positive correlation between MVD and VEGF in eutopic endometrium、ectopic endometrium (r=0.510,r=0.673,P<0.05,P<0.01),there was positive correlation between MVD and HIF-1αin eutopic endometrium、ectopic endometrium (r=0.559,r= 0.435, P<0.01,P<0.05),there was positive correlation between HIF-1αand VEGF in eutopic endometrium、ectopic endometrium (r=0.492,r=0.695,P<0.05,P<0.01).2 The content of E2、P、VEGF、CA125 in peritoneal fluid The level of E2 in peritoneal fluid was higer in EM group than in control group(P<0.05); The level of P in peritoneal fluid was lower in EM group than in control group(P<0.01); The level of VEGF in peritoneal fluid was higer in EM group than in control group (P<0.05); The level of CA125 in peritoneal fluid was higer in EM group than in control group(P<0.05).3 The observation of the curative effect and the changes of serum E2、P、VEGF、CA125 before and after treated by tonifying kidney warming yang removing blood stasis method3.1 The observation of the curative effect by tonifying kidney warming yang removing blood stasis method 30 patients with Endometriosis were treated by tonifying kidney warming yang removing blood stasis method. After treating,7 cases(22.86%)were healed,9 cases(28.57%) were excellent, 6 cases(25.71%)were effective and 8 cases(22.92%) were invalid. The total effective rate was 73.33%.3.2 The changes of serum E2、P、VEGF、CA125 before and after treated by tonifying kidney warming yang removing blood stasis methodAfter treated by tonifying kidney warming yang removing blood stasis method,compared with pre-T group, the level of serum E2 in post-T group was significantly decreased (P<0.01),with no statistical difference compared to control group(P>0.05), the level of serum P in post-T group was significantly increased (P<0.01),with no statistical difference compared to control group(P>0.05),the level of serum VEGF in post-T group was significantly decreased (P<0.01),with no statistical difference compared to control group (P>0.05),the level of serum CA125 in post-T group was significantly decreased (P<0.01),but still there were statistical differences compared to control group(P<0.01).Conclusion: Our studies demonstrates that the pathogene- sis and activity of endometriosis possibly depend of internal angiogenesis,the overexpression of VEGF and HIF-1αin endometriosis have a significant relation with angiogenesis,may play an important role in pathogenesis of endometriosis.The contents of VEGF、CA125、E2、P in EM are significant differently compared to control group,indicate that there are intimate relation among angiogenesis、sexual hormone and EM.Our study show that the tonifying kidney warming yang removing blood stasis method can cure endometriosis by decreasing the level of VEGF、regulating sexual hormone.更多还原