改良大鼠子宫内膜异位症模型的建立及微血管密度观察

目的对皮下筋膜层与腹壁肌层之间移植自体子宫内膜制作的子宫内膜异位症（endometriosis,EMs）模型进行评估。方法取10只雌性未交配性成熟大鼠,术前雌激素诱导,手术开腹取右侧子宫,将自体子宫内膜种植于双侧皮下筋膜层与腹壁肌层之间,术后第29天取出异位组织,进行组织形态学观察,免疫组织化学染色观察微血管密度（Microvessel density,MVD）。结果异位内膜在腹壁内生长,呈隆起囊状小包块,内有黏液,具有正常子宫内膜基本组织结构。异位内膜中微血管密度较在位内膜和正常子宫内膜高。结论此手术方法建立的大鼠子宫内膜异位症模型异位内膜病理改变与EMs患者类似,可以作为子宫内膜异位研究的动物模型。     

非动情期SD大鼠子宫内膜异位症模型的建立

目的　研究SD大鼠非动情期子宫内膜异位症建立方法和异位病灶的组织学形态及体液免疫反应。方法　采用外科诱导法对 40只非动情期和 40只动情期SD雌性大鼠行子宫组织自体移植手术。采集造模前后的血液进行体液免疫IgG、IgA、IgM、C3 、C4 的观察 ;手术后 7周取健侧子宫中段的在位内膜和移植的异位内膜行组织学研究。结果　SD大鼠非动情期进行子宫组织自体异位种植术成模率 95% ,与大鼠动情期进行子宫组织自体异位种植术成模率 94 8%比较 ,二者差异无显著性 ;异位内膜上皮细胞功能活跃 ,有类似正位子宫内膜的周期变化 ,其生理特征与正位子宫内膜基本相同。且造模后大鼠体液免疫反应敏感IgG、C3 增高 (P <0 0 1、3 P <0 0 5) ;IgM降低 (P <0 0 1)、IgA、C4 差异无显著性。结论　SD大鼠非动情期和动情期进行子宫组织自体异位种植术均可建立良好的子宫内膜异位症模型     

改良皮下种植法建立大鼠子宫内膜异位症模型

目的:采用改进的皮下种植法建立大鼠子宫内膜异位症的疾病模型,在保证成模的前提下,使皮下种植法建立大鼠子宫内膜异位症模型更加简单易操作,且成模效果更明显,术后易寻找病灶。方法:取性成熟期雌性SD大鼠10只,体重约250±5 g,术前五日连续给予苯甲酸雌二醇注射0.04 mg/每天,然后采用改良的皮下种植法建立大鼠子宫内膜异位症模型,既将大鼠自体双侧子宫切下,取其中一侧子宫种植至皮下血供较丰富处,术后第十日起连续五日给予苯甲酸雌二醇注射,于术后四周可观察腹部皮下病灶。结果:造模四周后见皮下种植的皮肤处有明显的圆形突起,切开皮肤可见种植的一侧子宫完整成活,与周围界限清晰,病灶明显易见,血运丰富。结论:实验结果证明此种方法较文献提供的皮下种植法更为简单易操作,省去了分离子宫内膜与肌层的步骤,且有病灶明显术后易寻找病灶的优点。     

子宫内膜异位症大鼠模型的建立及其病理学改变

目的构建子宫内膜异位症（内异症）大鼠动物模型,为阐明内异位症发病机理以及寻找有效的治疗方法提供理想的动物模型。方法取性成熟雌性Sprague-Dawley（SD）大鼠30只,通过手术将大鼠自体子宫组织移植到子宫旁韧带上,建立诱发型内异症大鼠动物模型。术后8周,再次剖腹观察异位组织的存活情况、病灶大小、与周围组织的粘连程度以及病理学变化。结果25只大鼠有明显的异位病灶。所有病灶都与周围组织有不同程度的粘连,病灶外观呈囊泡状。光镜观察见大部分异位子宫内膜形态和结构与在位子宫内膜基本相同,但内膜细胞、间质细胞、腺体,与在位内膜相比较少。少数病灶只有上皮组织或只有问质组织。结论自体子宫移植法可成功建立内异症大鼠模型。     

大鼠子宫内膜异位模型的建立与组织学观察

目的为开发诊治子宫内膜异位症(endometriosis,EMT)的新药研究提供理想的动物模型。方法取雌性未交配性成熟大鼠,术前雌激素诱导,麻醉开腹取部份右侧子宫,将内膜种植于左腹壁内,术后16周取出包块,进行组织形态学、组织化学观察。结果异位内膜在腹壁内生长,呈隆起囊状小包块,内有黏液,具有正常子宫内膜基本组织结构,囊腔较大。异位内膜中有糖原、RNA的存在。结论该手术方法建立的子宫异位内膜生长良好,术后一周就可摸及包块大小,为开发研究子宫内膜异位症的新药提供了方便。     

人子宫内膜异位症裸鼠模型的建立

目的建立人子宫内膜异位症裸鼠模型。方法通过开腹手术方法将人子宫内膜组织块种植于裸鼠盆腹腔,观察其生长情况,并进行病理检查。结果成功建立人子宫内膜异位症裸鼠模型,种植病灶能保持原有内膜组织的形态结构,并可见血管生成明显。结论子宫内膜异位症裸鼠模型的建立是子宫内膜异位症早期临床研究的理想模型。     

ERβ对子宫内膜异位症小鼠模型的影响

目的通过建立子宫内膜异位症小鼠模型探讨雌激素β受体对子宫内膜异位症的影响。方法利用雌激素β基因敲除小鼠建立自体子宫内膜异位模型;应用人不同的组织在SCID小鼠建立子宫内膜异位症模型后,注射雌激素β受体激动剂WAY-200070,观察其对异位病灶生长的影响。结果比较30只雌激素β受体基因敲除小鼠及22只同源未敲除小鼠异位病灶生长及组织细胞形态无明显差异（P〉0.05）;雌激素β受体激动剂WAY-200070对不同类型的SCID小鼠内异症病灶生长影响无明显差异（P〉0.1）。结论雌激素β受体对子宫内膜异位病灶的形成影响作用微弱。     

注射法小鼠皮下子宫内膜异位症模型及组织学观察

目的 建立ICR小鼠皮下子宫内膜异位症新的模型及组织学观察.方法 以同系小鼠作为供体,取子宫内膜分别采用皮下注射法和皮下植入法对2组共24只小鼠行皮下造模手术.3周后测量皮下种植结节大小,并处死半数造模成功小鼠,取子宫和异位结节行HE染色组织学研究.6周后,处死剩余小鼠,并再次测量皮下结节,取子宫和异位结节行HE染色组织学研究.结果 皮下植入法和皮下注射法成功率分别为33.33%和83.33%(P<0.01);生长良好的囊肿囊内壁有内膜上皮细胞生长,有与正位子宫内膜接近同步的发情周期改变;病灶随移植时间的推延先逐渐增大之后又有缩小趋势(P>0.05).结论 将ICR小鼠子宫内膜注射到同系小鼠腹部皮下形成子宫内膜异位病理模型,成功率高,且简单可行,异位内膜随动情周期有周期性改变,生理特性与正位子宫内膜基本相同,应用于子宫内膜异位症疾病和药物研究既经济又稳定可靠.     

雌激素受体β基因敲除小鼠子宫内膜异位症模型的建立

目的建立雌激素受体β基因敲除小鼠子宫内膜异位症模型,为进一步研究雌激素受体β基因在子宫内膜异位症发生发展过程中的作用提供平台。方法用外科手术方法对16只β基因敲除小鼠进行自体子宫移植,术后14d、21d取病灶组织进行光镜观察分析。结果建模成功率达95．8％,可形成明显囊肿,内含囊液,囊肿内壁有子宫内膜上皮细胞生长。结论应用本方法可建立稳定的子宫内膜异位症转基因小鼠模型,便于研究雌激素受体β亚型及其相关基因、蛋白在子宫内膜异位症发生发展过程中的作用机制。     

中药异位康冲剂治疗子宫内膜异位症小鼠的研究

目的：探讨中药异位康冲剂对小鼠子宫内膜异位症的作用及可能机理。方法：通过对小鼠一般情况、血常规、肝肾功及各主要脏器的组织学观察,观察中药异位康冲剂急性和长期毒副作用。通过一般情况、阴道脱落细胞观察、激素检测、病理组织学检查及血液流变学的改变,了解中药异位康冲剂对小鼠子宫内膜异位症模型的药理作用。结果：急性和长期毒性实验表明,中药异位康冲剂无明显毒性反应。异位康冲剂能抑制大鼠子宫内膜异位模型,降低血清雌二醇水平（P〈0.01）。病理学观察显示异位子宫的内膜腺体及腺上皮明显萎缩,其作用与丹那唑相似。结论：中药异位康冲剂无明显毒副作用,可促进子宫内膜异位组织细胞凋亡、抑制子宫内膜异位组织增殖,为临床用药提供了实验依据。     

Sprouted innervation into uterine transplants contributes to the development of hyperalgesia in a rat model of endometriosis

Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires.     

Subcutaneous endometriosis diagnosed by fine needle aspiration cytology

The fine needle aspiration cytology (FNAC) of two patients manifesting cutaneous/subcutaneous endometriosis is presented. Endometrial tissue sampled by the aspiration technique manifested different cytologic characteristics as compared to those of endometrial tissue obtained by standard exfoliative methods. A primary difference was the appearance of the endometrial cells in syncytial clusters in the aspirate, in contrast to the three-dimensional clusters seen in exfoliated material. These cases emphasize the need to include endometriosis in the differential diagnosis of palpable lesions of the abdominal wall, especially in women with healed surgical scars, and the role of FNAC in diagnosing such lesions.     

大鼠子宫内膜炎模型复制及其中西药复方乳剂治疗

目的人工复制大鼠子宫内膜炎模型;应用自制中西药复方乳剂对子宫内膜炎模型大鼠进行治疗。方法对实验大鼠子宫眼观病变、子宫内容物及单侧子宫指数进行检查,对实验大鼠子宫进行病理组织学检查。结果应用3％冰乙酸对大鼠子宫进行刺激,第4天对大鼠子宫接种混合病原菌,能够稳定复制大鼠子宫内膜炎模型;中西药复方乳剂能明显降低大鼠子宫内细菌浓度、种类及单侧子宫系数,能明显减轻子宫的病理变化。结论中西药复方乳剂对子宫内膜炎模型大鼠有良好的治疗作用。     

Estrous changes in vaginal nociception in a rat model of endometriosis

A rat model of endometriosis, in which pieces of uterine horn (versus fat in controls) are autotransplanted into the abdomen where they form cysts, reduces fecundity and produces vaginal hyperalgesia. The cysts gradually enlarge over a 2-month period postsurgically and then plateau. Cysts regress with low estrogen levels and reappear when they rise. Based on the hypothesis that the vaginal hyperalgesia depends upon the cysts, this study tested two predictions: that (1) the hyperalgesia would develop postsurgically in parallel with the cysts, and (2) the hyperalgesia would vary with estrous, being greatest when estrogen levels are high (proestrus) and least when low (estrus). In rats trained to escape vaginal distention, percentage escape responses to different distention volumes were measured across the rat's 4-day estrous cycle for 2.5 months before and up to 4 months after autotransplantation of uterus (n=9) or fat (n=6) in abdominal sites. Vaginal pressures were also measured. In rats with uterine but not fat autotransplants, escape percentages increased postsurgically over a 2-month period and then plateaued. The increase was greatest in proestrus and failed to occur in estrus. Vaginal pressures were unchanged in all groups. These results strongly support the hypothesis that the vaginal hyperalgesia depends upon the cysts. Because the cysts were located in sites remote from the vagina, the hyperalgesia involves viscero-visceral interactions and is likely centrally mediated, whereas the estrous modulation could involve hormonal actions either on the cysts or, more likely, on vaginal afferent fibers, and/or on central neurons.     

Fine needle aspiration cytology in cutaneous and subcutaneous endometriosis

OBJECTIVE: To study the role of fine needle aspiration cytology (FNAC) in the diagnosis of cutaneous and subcutaneous endometriosis. STUDY DESIGN: We present 7 cases of endometriosis in abdominal wall, inguinal region and perineum diagnosed by FNAC. All cases were confirmed with histologic follow-up. Cytologic and histologic material was prepared using standard methods. RESULTS: The smears were highly cellular, showing a hemorrhagic background with hemosiderin-laden macrophages and sheets of epithelial and stromal cells. Occasionally, these cellular components were closely associated. CONCLUSION: FNAC is useful in the diagnosis of cutaneous and subcutaneous endometriosis, providing a rapid and accurate preoperative diagnosis.     

Mouse model of surgically-induced endometriosis by auto-transplantation of uterine tissue

Endometriosis is a chronic, painful disease whose etiology remains unknown. Furthermore, treatment of endometriosis can require laparoscopic removal of lesions, and/or chronic pharmaceutical management of pain and infertility symptoms. The cost associated with endometriosis has been estimated at 22 billion dollars per year in the United States. To further our understanding of mechanisms underlying this enigmatic disease, animal models have been employed. Primates spontaneously develop endometriosis and therefore primate models most closely resemble the disease in women. Rodent models, however, are more cost effective and readily available. The model that we describe here involves an autologous transfer of uterine tissue to the intestinal mesentery (Figure 1) and was first developed in the rat and later transferred to the mouse. The goal of the autologous rodent model of surgically-induced endometriosis is to mimic the disease in women. We and others have previously shown that the altered gene expression pattern observed in endometriotic lesions from mice or rats mirrors that observed in women with the disease. One advantage of performing the surgery in the mouse is that the abundance of transgenic mouse strains available can aid researchers in determining the role of specific components important in the establishment and growth of endometriosis. An alternative model in which excised human endometrial fragments are introduced to the peritoneum of immunocompromised mice is also widely used but is limited by the lack of a normal immune system which is thought to be important in endometriosis. Importantly, the mouse model of surgically induced endometriosis is a versatile model that has been used to study how the immune system, hormones and environmental factors affect endometriosis as well as the effects of endometriosis on fertility and pain.