Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis

Purpose

The current study investigated the potential therapeutic efficiency of atosiban, an oxytocin receptor antagonist, in an experimental endometriosis model.

Methods

Endometriosis was surgically induced in 35 female rats during estrus. Four weeks after this procedure, relaparotomy was performed. The viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups. In the first group (n?=?8), a daily dose of 0.2?ml 0.9?% NaCl was injected intraperitoneally (i.p.) (control cases). In the second and third groups (n?=?8 and n?=?8), 0.5?mg/kg/day i.p. atosiban and 1?mg/day i.p. diltiazem were given, respectively. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriosis foci were recorded. The endometrial implants were processed for histological and immunohistochemical studies. The volumes of endometriotic implants were measured, and immunohistochemical analyses were performed, and compared between the groups.

Results

After the treatment with atosiban, volumes of endometriotic implants decreased significantly. Proliferating cell nuclear antigen expression levels were significantly reduced in the atosiban and diltiazem groups compared with the control group.

Conclusions

In a rat endometriosis model, atosiban, an agent used for the first time for the medical treatment of endometriosis, has shown significant therapeutic efficiency.     

Theranekron for treatment of endometriosis in a rat model compared with medroxyprogesterone acetate and leuprolide acetate

Objectives

The aim of this study was to compare the effects of theranekron, medroxyprogesterone acetate (MPA), and leuprolide acetate (LA) on surgically induced endometriosis in a rat model.

Study design

Endometriosis was surgically induced in forty female rats during estrus. After 3 weeks, a second operation was performed and the rats were randomized using a randomization table into theranekron, MPA, LA, and control groups. These treatments were continued for 3 weeks. A third operation was performed to evaluate treatment results. Then, the experimental treatments were halted and estrogen was initiated again to maintain estrus. After three additional weeks; i.e. after 9 weeks, the recurrence rate of endometrial foci was evaluated in a fourth operation and the rats were sacrificed. The volume of endometriotic foci and histopathology scores before and after treatment were compared.

Results

The respective mean volumes of the endometriotic foci after 3, 6, and 9 weeks were 86.4 ± 21.2, 16.4 ± 8.2, and 20.1 ± 9.6 mm³ in the theranekron group, 78.3 ± 20.4, 42.6 ± 13.5, and 66.7 ± 16.2 mm³ in the MPA group, and 91.8 ± 30.2, 34.4 ± 11.4, and 72.4 ± 21.9 mm³ in the LA group. The respective mean histopathology scores were 2.4 ± 0.6, 1.8 ± 0.6, and 1.6 ± 0.6 in the theranekron group, 2.5 ± 0.8, 2.0 ± 1.1, and 2.7 ± 1.0 in the MPA group, and 2.3 ± 0.5, 2.1 ± 1.2, 2.4 ± 0.8 in the LA group. After 9 weeks, the mean volume of endometriotic foci and histopathology scores were significantly lower in the theranekron group.

Conclusions

Theranekron caused more evident regression of endometriotic foci than MPA or LA in a rat model. After stopping the theranekron treatment, the recurrence rate was also lower than that of the other groups.     

缩宫素对大鼠子宫内膜异位症模型的治疗作用

目的:观察缩宫素对大鼠子宫内膜异位症(EMT)模型的治疗作用。方法:建模成功的SD大鼠随机分为缩宫素(OT)组和0.9%氯化钠液(NS)组各20只,OT组采用肌内注射OT 160μg/kg·d~(-1),NS组采用肌内注射0.9%氯化钠液0.1 ml/d。治疗4周后开腹观察异位病灶体积变化,应用RT-PCR、Western-blot检测治疗前后两组大鼠异位内膜组织中血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNF-α)、血小板反应素-1(TSP-1)mRNA及蛋白的表达水平。结果:(1)治疗前,OT组大鼠异位病灶体积(40.61±9.45 mm~3)与NS组(39.32±7.75 mm~3)比较,差异无统计学意义(P0.05)。治疗4周后,OT组大鼠异位病灶体积(15.21±3.11 mm~3)较NS组(39.59±7.65 mm~3)明显减小(P0.05)。NS组治疗前后异位病灶体积无明显变化(P0.05)。(2)OT组VEGF mRNA、TNF-αmRNA相对表达量(0.21±0.02,0.41±0.20)均较NS组(0.87±0.05,1.09±0.10)明显下降(P0.05);OT组TSP-1 mRNA的相对表达量(3.87±0.84)较NS组(0.96±0.25)明显升高(P0.05)。(3)OT组VEGF及TNF-α蛋白相对表达量(0.12±0.17,0.17±0.20)均较NS组(1.34±0.35,1.07±0.23)明显下降(P0.05);OT组TSP-1蛋白相对表达量(1.01±0.14)较NS组(0.33±0.07)明显升高(P0.05)。结论:缩宫素对大鼠EMT模型可能具有治疗作用,EMT病灶组织的高度血管化,可能与VEGF、TNF-α和TSP-1的表达失衡密切相关。     

棉酚引起雌鼠实验性子宫内膜异位症的快速消退

为研究棉酚对子宫内膜异位症的治疗作用及其机理，２４只经自体子宫内膜移植引起的实验性子宫内膜异位症雌鼠随机分成对照组和棉酚治疗组。对照组予以０．５％Ｔｗｅｅｎ８０皮下注射，棉酚组予以０．５％Ｔｗｅｅｎ８０溶释的棉酚混悬液以５ｍｇ／（ｋｇ·ｄ）皮下注射２～３周。结果表明，与对照组比较，经２～３周棉酚治疗的实验性子宫内膜异位症雌鼠卵巢重量和血浆雌二醇明显降低（Ｐ＜０．０１）；而子宫重量和子宫内膜移植病灶也明显减少（Ｐ＜０．０５），棉酚引起移植子宫内膜异位病灶消退率为６６．６％，研究证实：棉酚可有效地阻遏实验性子宫内膜异位病灶的生长发育并可使其快速消退，其作用部位在卵巢和子宫水平而非在下丘脑－垂体水平，实验进一步证实棉酚对子宫内膜异位症的治疗作用并可望开发成为新一代治疗药物。     

Studies on the surgical induction of endometriosis in the rat

As a model to examine the pathophysiologic attributes of endometriosis, attempts were made to surgically induce the disease in the rat by autotransplanting endometrial or uterine tissue to the peritoneum. Rats (n = 46) were randomly assigned to one of four surgical techniques: (1) four uterine squares sutured to the peritoneal cavity; (2) uterine luminal lavages instilled into the peritoneal cavity; (3) endometrial scrapings flushed into the peritoneal cavity; and (4) sham-operated controls. Rats were examined at various days after surgery for the presence of endometrial implants. The autotransplantation of uterine squares to the peritoneal cavity was the only treatment that yielded healthy endometriotic implants. These implants grew into ellipsoidal cystic structures that were composed of both endometrial glands and stroma and were found to contain prostaglandin F (202 ng/mg) at concentrations similar to those measured in uterine tissue (205 ng/mg). To examine the effect of surgically induced endometriosis upon fecundity, rats (n = 40) were autotransplanted with uterine squares or were sham operated and mated. The presence of ectopic endometrial tissue reduced the number of pups at term by 48% and the number of day 14 embryos by 28% (P less than 0.05). Peritoneal adhesions were greater in rats with induced endometriosis than in sham-operated controls (P less than 0.05); however, in rats with induced endometriosis, no differences were noted in the severity of adhesions between pregnant and nonpregnant rats. Endometriotic implants underwent complete regression in the day 14 pregnant rat but had doubled in size in the nonpregnant rat. At term, the endometriotic implants were larger than in the day 14 pregnant rat (P less than 0.05) and similar to their original size. The successful growth and development of surgically transplanted endometrial tissue in the rat offers a research model that can be used to study those aspects of endometriosis that cannot be adequately investigated in women.     

Remission of endometriosis by hyperbaric oxygen treatment in rats

We designed this prospective, randomized controlled animal study to determine the effects of hyperbaric oxygen (HBO) on experimentally induced endometriosis in a rat model. Surgical induction of endometriosis was performed in 40, nonpregnant, female, Wistar-Albino rats at the Experimental Medicine Research Center of Istanbul University (DETAE). Four weeks later, the first and second laparotomies for volume measurement and peritoneal fluid (PF) collection were performed, and the rats were divided randomly into the study and control groups. The study group was exposed to HBO treatment for 6 weeks. Then, a third laparotomy was performed on all of the rats. The volume, histopathologic scores, Ki-67 labeling of the endometriotic implants, and the levels of tumor necrosis factor-α (TNF-α) in the PF were measured. The mean volume of the endometriotic implants in the study group was significantly lower than that of the control group at the end of the study (57.4 ± 12.5 vs 94.6 ± 17.2 mm(3)). The mean histopathological scores (1.60 ± 0.50 vs 2.42 ± 0.51), Ki-67 immunohistochemical scores (1.50 ± 0.51 vs 2.37 ± 0.49) of the endometriotic implants, and the TNF-α levels (5.33 ± 1.02 vs 8.16 ± 1.76 pg/mL) were significantly lower in the study group than in the control group. Hyperbaric oxygen treatment for 2 hours a day for 6 weeks resulted in significant remission of endometriosis in rats.     

Endometriotic implants regress in rat models treated with puerarin by decreasing estradiol level

Phytoestrogens, which have a weak estrogenic effect, bind to estrogen receptors (ERs), thereby competing with estradiol, have an antiestrogenic effect on women of reproductive age with high estrogenic level. Herein, we examined the ability of the phytoestrogen Puerarin to treat endometriosis in rat models of endometriosis. In total, 75 adult, mature female Sprague-Dawley rats in which endometriotic implants were successfully induced by transplanting autologous endometrial tissue to ectopic sites were used in this study. Oral gavage of Puerarin (at doses of 600, 200, or 60 mg/kg per day) or Danazol (80 mg/kg per day) started 4 weeks after implantation. Control model rats received vehicle alone. After administration for 4 weeks, the weight of the ectopic implants, estradiol concentration, as well as ER-α and Aromatase P450 (P450arom) expression in different groups of rat tissues were evaluated after treatment. The endometriotic tissue weight and serum estrogen levels were significantly lower in high, medium, low dose of Puerarin and Danazol treatment groups than that in control group (P < .05 or P < .01). Low-dose Puerarin inhibited P450arom expression and significantly reduced estrogen levels in endometriotic tissue (P < .01). Three doses of Puerarin had no adverse effects on liver, kidney, and ovary, whereas high-dose Puerarin administration caused thinner bone trabecula with distortion and breakage and Danazol administration caused mild or moderate hepatic cell damage. These data demonstrate that Puerarin was able to effectively suppress the growth and development of ectopic endometrium in the rat endometriosis model, even at low doses, suggesting it may be an effective treatment for endometriosis.     

Comparison of the effect of isotretionin and alitretionin on endometriotic implants and serum vascular endothelial growth factor level: an experimental study

Objective: To compare the effects of alitretionin and isotretionin on endometrial peritoneal implants and serum vascular endothelial growth factor (VEGF) levels.

Study design: Forty-eight female Sprague Dawley rats were used. Initially surgical rat endometriosis model was done. The endometrial implant volume was measured and rats were randomly divided into four groups. Group 1: Control group (rats did not get any drug but having endometriotic implants), group 2: rats receiving po isotretionin 10?mg/kg per day for 10?d, group 3: rats receiving po isotretionin 20?mg/kg per day for 10?d and group 4: rats receiving po alitretionin 80?mg/kg per day for 10?d. After 1-week medication, rats were sacrificed and size, histopathology of endometriotic implant and levels of VEGF were evaluated.

Results: Volumes of peritoneal endometrial implants were significantly decreased in Group 2 and Group 3 compared with initial values. However, there were no significant changes in histopathological scores and serum VEGF levels in all groups.

Conclusions: This study finding may suggest the possible medical treatment modality of isotretionin on endometriosis. However, alitretionin (potent retinoid) does not have potent regressive effect on endometriotic implants as in isotretionin.     

Effect of caffeic acid phenethyl ester on the regression of endometrial explants in an experimental rat model

The objective of this study is to determine the effects of antioxidant and anti-inflammatory caffeic acid phenethyl ester (CAPE) on experimental endometriosis, peritoneal superoxide dismutase (SOD) and catalase (CAT) activities, and malondialdehyde (MDA) levels in the rat endometriosis model. Thirty rats with experimentally induced endometriosis were randomly divided into 2 groups and treated for 4 weeks with intraperitoneal CAPE (CAPE-treated group; 10 micromol/kg/d, n = 13) or vehicle (control group; n = 13). The volume and weight changes of the implants were calculated. Immunohistochemical and histologic examinations of endometriotic explants by semiquantitative analysis and measurements of peritoneal SOD, CAT, and MDA levels were made. Following 4 weeks of treatment with CAPE, there were significant differences in posttreatment spherical volumes (37.4 +/- 14.7 mm(3) vs 147.5 +/- 41.2 mm(3)) and explant weights (49.1 +/- 28.5 mg vs 158.9 +/- 50.3 mg) between the CAPE-treated groups and controls. The mean evaluation nomogram levels in glandular epithelium for COX-2 positivity by scoring system were 2.1 +/- 0.3 in the CAPE-treated group and 3.9 +/- 0.3 in the control group. In the CAPE-treated group, peritoneal levels of MDA and activities of SOD and CAT significantly decreased when compared with the control group (P < .01). Histologic analysis of the explants demonstrated mostly atrophy and regression in the treatment group, and semiquantitative analysis showed significantly lower scores in rats treated with CAPE compared with the control group. CAPE appeared to cause regression of experimental endometriosis.     

Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis.

Various types of cell adhesion molecules and matrix metalloproteinases (MMPs) seem to play an important role in the invasion process of endometriosis; however, limited investigation has focused on their gene expression in human peritoneal endometriotic lesions. A total of 63 endometriotic tissues were surgically obtained from 35 women with endometriosis, which included 43 pigmented and 20 non-pigmented lesions. Gene expression levels of E-cadherin, alpha- and beta-catenin, MMP-2, MMP-9 and membrane-type 1 (MT1)-MMP in these endometriotic lesions were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. MMP-2, MMP-9 and MT1-MMP mRNA expression in pigmented lesions was significantly higher than that in normal endometrium (p < 0.05), whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriotic lesions. There was a close correlation between MMP-2 or MT1-MMP and E-cadherin, alpha- or beta-catenin gene expression in 63 endometriotic tissues examined (p < 0.01). Immunohistochemical expression of E-cadherin, alpha- and beta-catenin in glandular epithelial cells was positive not only for all of seven cases with normal eutopic endometrium but also for 9 of 11 with ovarian endometriosis. MMP expression in ectopic endometrium was much greater than that in eutopic endometrium. These results suggest that endometriotic tissues expressing MMPs might be invasive and simultaneously possess cell-to-cell adhesion property in pelvic peritoneal foci.     

Endometriosis prophylaxis and treatment with the newly developed xenogenic immunomodulator RESAN in an animal model

Objective

The objective was to assess the effectiveness of the newly developed immunomodulator RESAN in the prophylaxis and treatment of endometriosis induced in rats.

Study design

The study was performed on 58 Wistar rats. Twelve weeks before endometriosis induction, the RESAN vaccine was administered to 24 rats (100 mg i.m. and 100 mg s.c.). Endometriosis induction was performed in 48 rats, which were divided into two groups: group I, the prophylaxis group, consisting of 24 previously vaccinated rats; and group II, the treatment group, comprising the other 24 rats, which had not been vaccinated. The graft (4 mm × 4 mm) of endometrium was attached to the parietal peritoneum. A sham operation was performed in 10 rats (group III). After 3 months, a second laparotomy was performed in all animals, and endometriotic foci were excised when present. RESAN was administered to the group II animals. After an additional 3 months, a third laparotomy was performed in all animals of the three groups.

Results

Positive, histologically confirmed endometriosis was found in 4.3% of the animals in group I and in 69.6% of group II rats (p < 0.0001). Macroscopic assessment revealed endometriosis in 21.7% and 91.3% of animals in groups I and II, respectively (p < 0.0001). At final laparotomy, 3 months after excision of the previously suspected foci, no signs of endometriosis were found according to both macroscopic assessment and histological examination. During the second laparotomy intraperitoneal adhesions were present in 13.0% of the animals in group I and in 61.0% of those in group II. No adhesions were present in group III. At the final laparotomy, the adhesions were present in only three of the animals in group II (p < 0.0009).

Conclusions

RESAN seems to be effective in both the prophylaxis and treatment of endometriosis, as well as in the prophylaxis of adhesions. Histological confirmation of endometriosis should be mandatory.     

Gene Expression Signature of Endometrial Samples from Women with and without Endometriosis

Study ObjectiveTo develop a prototype of a complex gene expression biomarker for the diagnosis of endometriosis on the basis of differences between the molecular signatures of the endometrium from women with and without endometriosis.DesignProspective observational cohort study. Evidence obtained from a well-designed, controlled trial without randomization.SettingDepartment of reproductive medicine and surgery, A.I. Evdokimov Moscow State University of Medicine and Dentistry.PatientsA total of 33 women (aged 32–38 years) were included in this study. Patients with and without endometriosis were divided into 2 separate groups. The group composed of patients with endometriosis included 19 living patients with endometriosis who underwent laparoscopic excision of endometriosis. The control group included 6 living patients who underwent laparoscopic excision of incompetent uterine scar after cesarean section, with both surgically and histologically confirmed absence of endometriosis and adenomyosis. An additional control/verification group included various previously RNA-sequencing–profiled tissue samples (endocervix, ovarian surface epithelium) of 8 randomly selected healthy female cadaveric donors aged 32 to 38 years. The exclusion criteria for all patients were hormone therapy and any intrauterine device use for more than 1 year preceding surgery, as well as absence of other diseases of the uterus, fallopian tubes, and ovaries.InterventionsLaparoscopic excision of endometriotic foci and hysteroscopy with endometrial sampling were performed. The cadaveric tissue samples included endocervix and ovarian surface epithelium. Endometrial sampling was obtained from the women in the control group. RNA sequencing was performed using Illumina HiSeq 3000 equipment (Illumina, Inc., San Diego, CA) for single-end sequencing. Unique bioinformatics algorithms were developed and validated using experimental and public gene expression datasets.Measurements and Main ResultsWe generated a characteristic signature of 5 genes downregulated in the endometrium and endometriotic tissue of the patients with endometriosis, selected after comparison with the endometrium of the women without endometriosis. This gene signature showed a capacity for nearly perfect separation of all 52 analyzed tissue samples of the patients with endometriosis (endometrial as well as endometriotic samples) from the 14 tissue samples of both living and cadaveric donors without endometriosis (area under the curve = 0.982, Matthews correlation coefficient = 0.832).ConclusionThe gene signature of the endometrium identified in this study may potentially serve as a nonsurgical diagnostic method for endometriosis detection. Our data also suggest that the statistical method of 5-fold cross-validation of differential gene expression analysis can be used to generate robust gene signatures using real-world clinical data.     

Surgical Neuropelviology: Combined Sacral Plexus Neurolysis and Laparoscopic Laterally Extended Endopelvic Resection in Deep Lateral Pelvic Endometriosis

ObjectiveSurgical demonstration of combined sacral plexus neurolysis and laparoscopic laterally extended endopelvic resection for deep lateral infiltrating endometriosis.DesignVideo showing principles of neurolysis and laparoscopic laterally extended endopelvic resection applied to endometriotic surgery.SettingUniversity tertiary referral center. Deep infiltrating endometriosis is an underestimated disease with real medical and clinical issues, recently classified as central pelvic endometriosis and lateral pelvic endometriosis further divided into superficial and deep according to the structures’ involvement [1]. The surgical removal of endometriotic foci remains the standard treatment. A wide knowledge of neuroanatomy and high skills in minimally invasive surgery are required to manage this challenging surgical scenario [2].InterventionsNew surgical approach for deep lateral infiltrating endometriosis based on the principles of lateral extended endopelvic resection and neuropelviologic surgery [3,4]. The patient was a 35-year-old woman, para 1, with neuropathic pain radiating to the left leg and a cyclic menstrual disorder. A laparoscopically assisted neuronavigation and subsequent neurolysis allowed the identification of the lateral nodule without damage to the autonomic pelvic innervation [1]. Then, a complete resection of the internal vascular compartment was required to obtain a radical endometriotic eradication. Shaving and bladder resection were also performed to complete removal of the endometriotic foci.ConclusionThe association of neuroanatomic knowledge and surgical oncologic principles applied to minimally invasive surgery should be considered to ensure an adequate surgical radicality and clinical benefit in patients with deep infiltrating endometriosis.     

Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis

Various types of cell adhesion molecules and matrix metalloproteinases (MMPs) seem to play an important role in the invasion process of endometriosis; however, limited investigation has focused on their gene expression in human peritoneal endometriotic lesions. A total of 63 endometriotic tissues were surgically obtained from 35 women with endometriosis, which included 43 pigmented and 20 non-pigmented lesions. Gene expression levels of E-cadherin, α- and β-catenin, MMP-2, MMP-9 and membrane-type 1 (MT1)-MMP in these endometriotic lesions were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. MMP-2, MMP-9 and MT1-MMP mRNA expression in pigmented lesions was significantly higher than that in normal endometrium (p < 0.05), whereas E-cadherin, α- and β-catenin mRNA expression was not suppressed in endometriotic lesions. There was a close correlation between MMP-2 or MT1-MMP and E-cadherin, α- or β-catenin gene expression in 63 endometriotic tissues examined (p < 0.01). Immunohistochemical expression of E-cadherin, α- and β-catenin in glandular epithelial cells was positive not only for all of seven cases with normal eutopic endometrium but also for 9 of 11 with ovarian endometriosis. MMP expression in ectopic endometrium was much greater than that in eutopic endometrium. These results suggest that endometriotic tissues expressing MMPs might be invasive and simultaneously possess cell-to-cell adhesion property in pelvic peritoneal foci.     

Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole.

OBJECTIVE: To investigate the effects of the immune modulators levamisole and loxoribine in a rat model of endometriosis. DESIGN: Prospective, placebo-controlled study. SETTING: Hospital-based research facility. ANIMAL(S): Nineteen rats with experimentally induced endometriosis. INTERVENTION(S): Rats were treated with three weekly intraperitoneal injections of levamisole (2 mg per rat; n = 6), loxoribine (1 mg per rat; n = 6), or saline (control; n = 7) and killed 8 weeks after treatment. MAIN OUTCOME MEASURE(S): Histologic and immunohistochemical analysis of endometriotic explants. RESULT(S): The loxoribine-treated group showed marked regression of both epithelial and stromal components. Epithelial regression was noted in the control group, but the epithelium was strikingly preserved in the levamisole group. There were significantly greater numbers of dendritic cells in the explants of animals treated with loxoribine and levamisole. The number of natural killer cells was significantly reduced in loxoribine-treated explants. CONCLUSION(S): Loxoribine, a potent immunomodulatory drug, appeared to cause regression in both stromal and epithelium components in a rat model of endometriosis. Further, specific cell-mediated immune responses in this model of endometriosis were elucidated.     

The effect of estradiol on the production and secretion of complement component 3 by the rat uterus and surgically induced endometriotic tissue

We have recently demonstrated that glandular epithelial cells isolated from human endometriotic tissue synthesize and secrete complement component 3 (C3). Furthermore, because C3 is capable of producing many of the immunological activities known to be associated with human endometriosis, we studied the production, secretion, and regulation of C3 using the rat model for endometriosis. Endometriosis was surgically induced in 20 adult female rats. The animals were then ovariectomized and one half were treated with estradiol (E2) for 3 days. Uterine luminal epithelial cells synthesized and secreted C3 only after E2 administration, whereas the uteri from control animals did not produce C3. In contrast, the ectopic endometrium from control animals produced and secreted C3, and this expression was strongly upregulated by in vivo E2 administration. We conclude that surgically induced endometriosis in the rat has properties biochemically independent from the intact uterus and may serve as a useful model to further investigate the regulation of C3 synthesis from human endometriosis.     

Histologic study of ovarian endometriosis after hormonal therapy

To evaluate the persistence of endometriosis and the morphologic changes occurring in endometriotic foci after hormonal therapy, microsurgical resection of ovarian endometriosis was performed in 148 women. After hormonal therapy (n = 116), a high prevalence of active endometriosis without signs of degeneration was found. Mitotic index was similar in the group of untreated women (n = 32) and in the three groups of women treated either with lynestrenol (Organon, Oss, The Netherlands), gestrinone (Roussel UCLAF, Paris, France), or buserelin (Hoechst, Frankfurt, West Germany). In conclusion, hormonal treatment leads to an incomplete suppression of endometriotic foci.     

沙立度胺对大鼠子宫内膜异位组织中VEGF及TNF-α表达的影响

目的:探讨沙立度胺(thalidomide,THD)对大鼠子宫内膜异位组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)和肿瘤坏死因子-α(tumornecrosis factor-alpha,TNF-α)表达的影响。方法:自体移植子宫内膜组织至腹膜,用SD大鼠建立子宫内膜异位症动物模型,3周后随机将建模成功的24只大鼠分为4组,每组6只,其中3组分别腹腔注射沙立度胺5mg/kg、20mg/kg和40mg/kg,模型对照组腹腔注射生理盐水,每天1次,连用4周。治疗结束后处死大鼠,获取异位子宫内膜组织。用免疫组化(SP)法测定VEGF和TNF-α在异位内膜的表达。结果:不同剂量THD给药组VEGF和TNF-α的表达均低于对照组(P0.05),其中以沙立度胺40mg/kg组最为明显。结论:THD可以抑制VEGF和TNF-α表达,从而发挥抗EMs血管生成作用,且其对VEGF和TNF-α表达的影响具有量效关系。     

Efficacy comparison of oral rosuvastatin versus oral progesterone and bevacizumab on regression of surgically endometriotic implants in rats

This study hypothesizes that oral rosuvastatin, oral dienogest and intraperitoneal bevacizumab might improve endometriosis in randomly selected female Wistar albino rats with surgically endometriotic implants. Thirty female Wistar albino rats with surgically endometriotic implants were randomized into three treatment groups: oral rosuvastatin (20?mg kg/day; oral rosuvastatin group 1; n?=?10), oral progesterone (dienogest group 2; n?=?10) and intraperitoneal bevacizumab (2.5?mg/kg of single intraperitoneal injection of bevacizumab; bevacizumab group 3; n?=?10), for 10 days. Post-treatment variables were compared. The oral rosuvastatin group showed higher reduction for the glandular epithelium and uterine vessels of histopathological scores values than the oral progesterone group (both, p?p?>?0.017). Endometrial thickness values and uterine volume values were more significantly reduced in the oral rosuvastatin group than the oral progesterone group (both, p?p?>?0.017). In conclusion, oral rosuvastatin and intraperitoneal injection of bevacizumab may cause more significant regression of surgically endometriotic implants in rats than oral progesterone medications.     

促黄体激素释放激素类似物与低剂量炔诺酮联合治疗子宫内 …

目的 了解国产促黄体激素释放激素类似物（ＬＨＲＨ－ａ）与低剂量炔诺酮联合治疗子宫内膜异位症（内异症）的疗效及安全性。方法 将７例内异症患者随机分为两组，Ａ组３６例，采用ＬＨＲＨ－ａ１５０μｇ每日肌内注射（肌注）＋炔诺酮２．５ｍｇ每日口服治疗；Ｂ组４１例，单独应用ＬＨＲＨ－ａ肌注、疗程３－６个月。观察治疗前后症状、体征、肝、肾功能、血脂代谢、骨代谢生化指标及右侧胫骨超声速度（ＳＯＳ）变化。结果 Ａ组