Rat Uterine Horn Research Articles

Increased adhesion formation after gelatin-thrombin matrix application in a rat model.

To evaluate the effects of gelatin matrix and thrombin-based hemostatic sealant agents (gelatin-thrombin matrix) on postoperative adhesion formation in the rat uterine horn model. A total of fourteen female Wistar-Albino rats were used in our postoperative adhesion formation model. Both uterine horns were exposed by midline incision with sterile technique and each uterine horn was traumatized by bipolar electrocautery. Before closure of the abdomen, 0.9% NaCl solution was administered intraperitoneally in the control group and the gelatin-thrombin matrix was applied on the traumatized areas on the uterine horns of the rats in the study group. At day 21 after the first surgery, the intraperitoneal macroscopic adhesion scores and the extent of fibrosis, inflammation scores, inflammatory cell activities, inflammation types of adhesion tissues, and the level of free oxygen radicals [malondialdehyde (MDA)] and antioxidant enzyme activity [superoxide dismutase (SOD) and glutathione S-transferase (GST)] in the uterine horn tissue were measured. There was no statistically significant difference between the two groups in terms of macroscopic adhesion scores (p=0.064), MDA levels (p=0.121), and GST activity (p=0.360). However, there was statistically significant difference between the two groups in terms of the extent of fibrosis (p<0.001), inflammation score (p=0.001), inflammatory cell activity (p=0.002), and SOD activity (p<0.001). Gelatin-thrombin matrix was found to have increased the extent of fibrosis, inflammatory cell activity, and inflammation score, and reduced the activity of SOD, which acts to prevent cell damage.

A randomized controlled study of the efficacy of misoprostol and hyaluronic acid in preventing adhesion formation after gynecological surgery: a rat uterine horn model

ObjectiveTo investigate the effect of misoprostol in the reduction of adhesion formation after gynecological surgery. Study designA double blind, randomized controlled experimental study was designed. Twenty-one female Wistar Hannover rats were divided into three groups as control, misoprostol and Hyalobarrier® groups. A uterine horn adhesion model was created. After anesthesia induction, 1.5–2cm injuries were made to the each uterine horn by cautery. The control group received no special medications except for the standard surgical procedure. The misoprostol group received 10μcg/kg misoprostol in addition to the standard surgical procedure, and the Hyalobarrier® group received 1cm3 ready-for-use Hyalobarrier® gel intraperitoneally in addition to the standard surgical procedure. After 14 days from the first surgical procedure, adhesion scores were evaluated. ResultsThe extent (p<0.001), severity (p<0.001), degree (p<0.001) and total adhesion score (p<0.001) values of the control group were statistically higher than the values of misoprostol and Hyalobarrier® groups. The inflammation score value of misoprostol group was statistically lower than control and Hyalobarrier® groups (p<0.001). ConclusionIn this study, we have found a new therapeutic potential of misoprostol that may be useful in preventing pelvic adhesion and reducing inflammation scores.

Tranexamic acid and hyaluronate/carboxymethylcellulose create cell injury.

Background and Objectives:Postoperative pelvic adhesions are associated with chronic pelvic pain, dyspareunia, and infertility. The aim of this study was to evaluate the adhesion prevention effects of tranexamic acid (TA) and hyaluronate/carboxymethylcellulose (HA/CMC) barrier in the rat uterine horn models on the basis of macroscopic and microscopic adhesion scores and histopathological as well as biochemical parameters of inflammation.Methods:Twenty-one Wistar rats were randomly divided into 3 groups. Ten lesions were created on the antimesenteric surface of both uterine horns by bipolar cautery. Three milliliters of 0.9% sodium chloride solution were administered in the control group. A single layer of 2 × 2 cm HA/CMC was plated in group 2. Two milliliters of TA was applied in the last group. All rats were sacrificed at postoperative day 21.Results:No significant difference was found among the control group, the HA/CMC group, and the TA group in terms of macro-adhesion score (P = .206) and microadhesion score (P = .056). No significant difference was found among the 3 groups in terms of inflammation score (P = .815) and inflammatory cell activity (P = .835). Malondialdehyde levels were significantly lower in the control group than in the TA group and HA/CMC group (P = .028). Superoxide dismutase and glutathione S-transferase activities were found to be higher in the control group than in the TA group (P = .005) and HA/CMC group (P = .009).Conclusions:TA and HA/CMC had no efficacy in preventing macroscopic or microscopic adhesion formation and decreasing inflammatory cell activity or inflammation score in our rat models. TA and HA/CMC increased the levels of free radicals and reduced the activities of superoxide dismutase and glutathione S-transferase enzymes, which act to reduce tissue injury.

Sıçan uterin horn modelinde enoksaparin ve rapamisinin adezyon oluşumuna etkilerinin karşılaştırılması

Aim. Several studies have demonstrated that low molecular weight heparins (LMWHs) decreased postoperative adhesion formation. Also, a few studies have noted that immunosuppressive agent rapamycin decreased postoperative adhesion formation. In this experimental study, we aimed to investigate the effect of enoxaparin and rapamycin alone and in combination on the adhesion formation in a rat uterine horn model. Methods. Our study included 40 Wistar-Albino rats weighing between 200-250 g. Control and three study groups were formed including 10 rats. In sterile condition, we performed 3-cm midline incision of abdominal wall under general anesthesia. On the antimesenteric surface of both uterine horns, 8-10 unipolar electrocauterization were applied. Later these antimesenteric surfaces were sutured to abdominal sidewalls with 4.0 polydioxanone. In the control group, no therapy was applied after surgery and incision was closed according to general surgical rules. In the enoxaparin group, enoxaparin 50 U/kg was applied intraperitoneally for 14 days. In the rapamycin group, rapamycin 0.8 mg/kg was applied orally with feeding tube for 14 days. In the enoxaparin plus rapamycin group, enoxaparin 50 U/kg was applied intraperitoneally and rapamycin 0.8 mg/kg orally with the feeding tube for 14 days. The animals were sacrificed by lethal dose pentobarbital 14 days after surgery and a midline laparatomy was carried out and abdominal cavity was inspected for the presence of adhesion and adhesion samples were obtained for histopathological examination. Results. According to the findings of macroscopic and microscopic evaluation, the scores of adhesion severity were found comparable among the enoxaparin, rapamycin and enoxaparin plus rapamycin groups (p>0.05); however, the scores of adhesion extent and total adhesion scores were significantly lower in the drug groups compared to the control group (p 0.05). Conclusion. Enoxaparine and rapamycin prevent total adhesion similarly, however, this effect is considerable on the extent of adhesion rather than the severity of adhesion. Combination of enoxaparin and rapamycin did not show synergistic effect on adhesion formation.

Comparison of effects of enoxaparin and rapamycin on adhesion formation in a rat uterine horn model

Comparison of effects of enoxaparin and rapamycin on adhesion formation in a rat uterine horn model

Lipoic acid decreases peritoneal adhesion formation in a rat uterine scar model

To investigate the effects of lipoic acid in the prevention of postoperative pelvic adhesions by a visual scoring system and immunohistochemistry in a rat uterine horn model with full thickness injury. Twenty-eight female Wistar albino rats were randomised into four groups: uterine trauma control, 15 days and 30 days, and uterine trauma + lipoic acid, 15 days and 30 days. A full thickness defect was established by incising a segment of approximately 1.0 cm in length from each uterine horn, leaving the mesometrium intact. Extension and severity of the adhesions in each group were scored by a visual scoring system and evaluated immunohistochemically. Adhesion scores were 2.00±0.81, 2.14±0.69 0.71±0.75, and 0.85±0.69 for extent and 2.28±0.48, 2.14±0.69, 0.85±0.69, and 1.14±0.69 for severity in Groups 1, 2, 3 and 4, respectively. Adhesion extent and severity were significantly less for groups treated by lipoic acid but no difference was observed between long and short administration. Both Vitronectin and u-PAR staining were significantly increased in treatment groups when compared to the control group. Lipoic acid was found to be effective in reducing postoperative adhesion formation in a rat model.

The aromatase inhibitor letrozole reduces adhesion formation after intraperitoneal surgery in a rat uterine horn model

To investigate, in an experimental animal study, the effects of letrozole and tamoxifen in the reduction of adhesion formation following abdominopelvic surgery. Thirty female Wistar albino rats were included and divided into three groups. One group received 500 μg/d tamoxifen and a second group received 1 mg/kg/d letrozole through an enteric tube. A third group did not receive any drugs and served as the control group. On the fifth day, a laparotomy was performed and the right uterine horn was injured by monopolar cautery. The left uterine horn was incised with a scalpel and sutured. The preventive therapy protocols were continued for 7 days after surgery. On the 14th day after first surgery the animals were sacrificed, and the intraperitoneal macroscopic adhesion formation and microscopic adhesion features were evaluated. The Kruskal-Wallis test was used to compare the scores of the macroscopic adhesion scores and histologic features among the three groups, followed by a post hoc Mann-Whitney test. The total histological score was analyzed with a one-way ANOVA, followed by post hoc Bonferroni correction tests. p values ≤0.05 were considered statistically significant. The level of significance was set at p≤0.016 for the post hoc tests. The letrozole and tamoxifen groups had significantly lower adhesion scores for the right uterine horn than the control group (p=0.005 and p=0.013, respectively). For the left horn, however, only the letrozole group had a lower macroscopic adhesion score than the controls (p=0.011). The total histological score was significantly lower in the letrozole group than in the control group (p=0.014), but no differences were found between the tamoxifen group and the control group (p=0.954). Inflammation, fibroblastic activity, collagen formation and vascular proliferation were significantly lower in the letrozole group compared with the control group (p<0.05). The foreign body reactions were similar among the three groups (p>0.05). Tamoxifen administration did not result in any significant effects on the histological scores (p>0.05). Letrozole resulted in a significant decrease in postoperative macroscopic adhesion formation and the total histological scores, but tamoxifen did not demonstrate a similar effect on the histological scores.

The effect of lipoic acid on wound healing in a full thickness uterine injury model in rats

Aim of this study was to investigate the effects of lipoic acid on uterine wound healing by immunohistochemical and biochemical assay in a rat uterine horn model with full thickness injury. Thirty-two female Wistar albino rats were randomised into five groups: Control group, with no intervention; uterine scar group 15days (US15d), uterine scar group 15days+alpha lipoic acid (ALA) (US15d+ALA), uterine scar group 30days (US30d) and uterine scar group 30days+ALA (US30days+ALA). After uterine incision 100mg/kg of ALA was administered by oral gavage for either 15 or 30days. Vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA) distribution were evaluated by immunohistochemical methods in tissue and ELISA methods in tissue homogenate. The percentage of α-SMA positive area in US15d+ALA and US30d+ALA groups was significantly higher than US15 and US30d groups. The percentage of VEGF positive area in US15d+ALA group was significantly higher than US15d group and US30d+ALA group was significantly higher than US30d group. Biochemically, α-SMA was significantly higher in the US15d+ALA group when compared to US15d group and higher in US30d+ALA group when compared to US30d group. VEGF was significantly higher in US15d+ALA and US30d+ALA groups when compared to US15 and US30d groups. In conclusion, ALA was found to be effective in enhancing wound healing in uterine full thickness injury.

Comparison of the Effects of Meloxicam and Dexketoprofen on Postoperative Adhesion Formation in a Rat Uterine Horn Surgical Model

Study ObjectiveTo compare the effects of 2 nonsteroidal antiinflammatory drugs of different chemical classes (meloxicam and dexketoprofen) on postoperative intraabdominal adhesion formation in a rat model. DesignExperimental study (Canadian Task Force classification I). SettingCenter for research and development. AnimalsThirty female Wistar albino rats. InterventionsThe animals were randomly assigned to 1 of 3 groups (10 rats per group) and received intramuscular injections of 0.5 mg/kg dexketoprofen (group 1), 0.5 mg/kg meloxicam (group 2), or 1 mL sterile saline solution (control; group 3) daily for 2 days. Laparotomy was performed, and 1 of the uterine horns was damaged via monopolar electrocautery, whereas an incision was made in the other horn using a scalpel and was sutured to promote adhesion formation. The surgeons were blinded to the treatment method. Drug administration was continued for 5 days. The animals were euthanized at 14 days after surgery. Measurements and Main ResultsIntraperitoneal macroscopic and microscopic adhesions were assessed using standard adhesion scoring systems. Macroscopic adhesion scores were similar among the 3 groups in each horn (p > .50). The total histologic score was significantly lower in the meloxicam group than in the control group (8.0 vs 15.5; p = .006). Dexketoprofen did not significantly affect the total histologic score (11.0 vs 15.5; p = .09) or individual items (i.e., inflammation, fibroblastic activity, foreign body reaction, collagen formation, and vascular proliferation) compared with the control group (p > .02). Meloxicam significantly inhibited inflammation and collagen formation compared with the control group (p < .02). Meloxicam was also significantly superior to dexketoprofen in reducing inflammation (p = .006). ConclusionAlthough meloxicam did not affect clinical adhesion formation, it significantly decreased histologic scores compared with those of the control group. Therefore, meloxicam may be suitable in reducing postoperative intraabdominal adhesion formation.

Acetaldehyde Content and Oxidative Stress in the Deleterious Effects of Alcohol Drinking on Rat Uterine Horn

After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a severe atrophy in the rat uteirne horn was observed, accompanied by significant alterations in its epithelial cells. Microsomal pathway of acetaldehyde production was slightly increased. Hydroxyl radicals were detected in the cytosolic fraction, and this was attributed to participation of xanthine oxidoreductase. They were also observed in the microsomal fraction in the presence of NADPH generating system. No generation of 1-hydroxyethyl was evidenced. The t-butylhydroperoxide-induced chemiluminescence analysis of uterine horn homogenates revealed a significant increase in the chemiluminiscence emission due to ethanol exposure. In the animals repeatedly exposed to alcohol, sulfhydryl content from uterine horn proteins was decreased, but no significant changes were observed in the protein carbonyl content from the same samples. Minor but significant decreasing changes were observed in the GSH content accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant finding was the diminished activity content of glutathione peroxidase. Results suggest that acetaldehyde accumulation plus the oxidative stress may play an additional effect to the alcohol-promoted hormonal changes in the uterus reported by others after chronic exposure to alcohol.

Effect of Human Amniotic Fluid on Prevention of Postoperative Peritoneal Adhesion Formation in a Rat Uterine Horn Model

Effect of Human Amniotic Fluid on Prevention of Postoperative Peritoneal Adhesion Formation in a Rat Uterine Horn Model

Blood supply as a factor regulating pacemaker activity of the rat uterine horn

Effect of ischemia of the uterine artery supplying with blood the main rhythmogenic zone (the ovarian region) of the uterine horn on parameters of activity both of this locus and of all subsequent pacemaker areas up to the uterine cervix was studied in non-pregnant rats. The most pronounced changes in characteristics of the activity (amplitude, frequency, and burst genesis duration) were revealed in the ovarian horn end. The uterine corpus and the horn cervical end were less affected by ischemia. Meanwhile, under these conditions, amplitude of the slow-wave oscillations rose more than 1.5 times. The obtained data allow us to conclude about the presence of a certain connection between the horn ovarian end and the uterine cervix. Morphological studies have revealed strong vascularization of the upper part of uterine horn.

Resveratrol inhibits postoperative adhesion formation in a rat uterine horn adhesion model

Aim: Adhesion formation is one of the most important problems occuring after pelvic surgery in the majority of women. The aim of this experimental study was to investigate the effects of the antioxidant resveratrol (3,5,4′-o-trihydroxystilbene) on adhesion formation in a rat uterine horn adhesion model.Materials and methods: Thirty Wistar-Albino female rats were randomly divided into three groups with equal numbers. In Group A, 5.9 mg/kg/day resveratrol was applied by the orogastric route for 10 days before and 20 days after surgery. In Group B, resveratrol was given only for 20 days after surgery. In the control group, no drug was applied before or after surgery. A uterine serosal injury was created using a standard technique after laparotomy in all rats. All animals were sacrificed 3 weeks after surgery and intrapelvic adhesions determined macroscopically and microscopically.Results: Adhesion formation, total adhesion score and the severity of adhesions were all significantly lower in both resveratrol treatment groups than in the control group (p < 0.05). Notably, the severity of adhesions was much less in Group A in which the rats received resveratrol before and after surgical operation.Conclusions: This study suggests that 5 ± 1 mg/kg/day perioperative resveratrol administration is an effective strategy for the prevention of postoperative peritoneal adhesion formation after pelvic surgery in a rat model.

The effect of collagen-binding vascular endothelial growth factor on the remodeling of scarred rat uterus following full-thickness injury

Serious injuries of uterine which lead to scar formation will finally result in infertility or pregnancy complications. There are few effective methods to treat such damages because of the shortage of native tissues. Vascular endothelial growth factor (VEGF) is important for the formation of new vessels and re-epithelialization of endometrium. Here we produced a collagen-binding VEGF by fusing a collagen-binding domain to the N-terminal of native VEGF. After injection into a rat scarred uterus model (partial of rat uterine horn was excised and left for scar formation) the collagen targeting VEGF promoted remodeling of the scarred uterus including the regeneration of endometrium, muscular cells, and vascularization and improved pregnancy outcomes. Thus, collagen-binding VEGF may be a pragmatic solution for the treatment of severe uterine damages.

Evaluation of the effects of gonadotropin-relasing hormone antagonist (GnRH-ant) and agonist (GnRH-a) in the prevention of postoperative adhesion formation in a rat model with immunohistochemical analysis

To investigate the effects of GnRH antagonist (GnRH-ant) and agonist (GnRH-a) in the prevention of postoperative pelvic adhesions by a visual scoring system and immunohistochemical methods in a rat uterine horn model. Controlled experimental animal study. Animal laboratory at an academic research environment. Twenty-one Wistar albino rats. Rats were randomized into three groups. One week before the operation the rats received either GnRH-ant or GnRH-a or saline solution; they then underwent surgical laparotomy, and both uterine horns were traumatized by a scalpel. Three weeks later, all rats were sacrificed and extension and severity of the adhesions in each group were scored by a visual scoring system. Adhesion tissues were evaluated immunohistochemically for vitronectin and u-PAR. Scores of extend and severity of adhesions and staining of vitronectin and u-PAR. The extent of adhesion scores were 1.85 ± 0.86, 0.78 ± 1.05, and 0.42 ± 0.64, and the severity of adhesion scores were 1.71 ± 0.91, 0.57 ± 0.85, 0.50 ± 0.75 for control, GnRH-ant, and GnRH-a groups, respectively. The extent and severity of adhesions were significantly lower in both GnRH-ant and GnRH-a groups when compared with the control group. Adhesion extent scores in the GnRH-a group were lower than in the GnRH-ant group, but this difference was not significant. vitronectin and u-PAR staining were significantly greater in both the GnRH-ant and GnRH-a groups than in the control group. GnRH-ant as well as GnRH-a reduced postoperative adhesion formation in a rat model. This finding was supported immunohistochemically by vitronectin and u-PAR staining.

Reduction of postoperative adhesions by trimetazidine: an experimental study in a rat model

Trimetazidine (TMZ) reduces intracellular acidosis and inhibits oxygen-derived free radicals and neutrophile infiltration in ischemia and hypoxia, which are the primary steps of adhesion formation. Our aim is to study the anti-adhesion potential of trimetazidine in a rat uterine horn model. Forty non-pregnant female Wistar-Albino rats were randomly assigned, with ten in each group, to receive 2 ml saline, or 5 mg/kg intraperitoneal trimetazidine postoperatively, and control and sham. TMZ was administered to TMZ postoperative group 5 mg/kg i.p. daily for 5 days after the operation. Both uterine horns were exposed, and then a 2 cm segment of the anti-mesenteric surface of both the uterine horns were traumatized in 10 spots with unipolar electrocautery for 2 s with a power of 50 Watts. All the animals were killed by lethal dose of ether on postoperative 14th day. Intraperitoneal adhesions were scored by clinical adhesion scoring system, and histological and morphometric analysis was performed. Total adhesion score (TAS) of control group was 10 while the sham group was found to be 0. TAS of the placebo group that was given saline (TAS 5), and postoperative TMZ applied group (TAS 3.5) were significantly lower than the control group (p < 0.05). The severity scores of postoperative TMZ and sham groups were significantly smaller than the other groups (p < 0.05). TMZ significantly reduced the extent and severity of horn adhesions. The promising efficacy demonstrated by the intraperitoneal TMZ in this model warrants further investigation in clinical trials focused on gynecological procedures.

Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth factor

Severe damages of uterine endometrium which prevent embryos from implantation and placentation finally often result in infertility or pregnant complications. There is lack of effective treatments due to the limitation of native materials available and complexity of the function and internal environment of uterus. In the present study, a collagen targeting basic fibroblast growth factor (bFGF) delivery system was constructed by a collagen membrane loaded with bFGF fused a collagen-binding domain (CBD) to the N-terminal which limits the diffusion of bFGF from collagen. We tested the bFGF delivery system in rats under the severe uterine damage model (partial rat uterine horn excision/reconstruction), and found this delivery system improved regeneration abilities of uterine endometrium and muscular cells, improved vascularization, as well as better pregnancy outcomes in rats. Therefore, this targeting delivery system may be an effective strategy for uterine tissue regeneration.

The effects of the calcium channel agonist, Bay K-8644, on guinea-pig ileum and rat uterine horn

Bay K-8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2- trifluoromethylphenyl)pyridine-5-carboxylate) concentration-dependently caused contractions of the partly depolarized ileum, but at higher concentrations (10(-6) to 10(-5) M) produced relaxation. 10(-8) to 4 X 10(-7) M nifedipine antagonized while 10(-9) and 4 X 10(-9) M potentiated Bay K-8644. On the partly depolarized uterus, Bay K-8644 (10(-9) to 10(-6) M) had only a spasmogenic effect whereas nifedipine (4 X 10(-9) to 10(-7) M) was spasmolytic. Verapamil and diltiazem (each at 10(-4) M) both reduced the maximal response to Bay K-8644, while other spasmolytics were ineffective. Thus, Bay K-8644 activates ileum and uterus by opening voltage-operated Ca2+ channels, but its relaxant action at high concentration and its potentiation by nifedipine is not seen in both organs. Such differences probably depend on the concentration of the compounds used and the polarization state of the cell membranes.

Angiogenesis in Rat Uterine Cicatrix after Injection of Autologous Bone Marrow Mesenchymal Stem Cells

Results of injection of autologous bone marrow mesenchymal stem cells with transfected GFP gene into the rat uterine horn cicatrix were studied by light microscopy. Large groups of blood vessels with blood cells inside were seen after injection of autologous bone marrow cells into the cicatrix on the right horn, formed 2 months after its ligation; no groups of vessels of this kind were found in the cicatrix in the contralateral horn. Examination of unstained sections in reflected UV light showed sufficiently bright fluorescence in the endothelium and outer vascular membrane in the uterine horn cicatrix only on the side of injection. Hence, autologous mesenchymal stem cells injected into the cicatrix formed the blood vessels due to differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in the vascular endothelium, but also in vascular outer membranes indicated that autologous mesenchymal stem cells differentiated in the endothelial and pericytic directions.

Effect of bevacizumab on postoperative adhesion formation in a rat uterine horn adhesion model and the correlation with vascular endothelial growth factor and Ki-67 immunopositivity

We investigated whether adhesion formation is prevented by the inhibition of angiogenesis in a rat uterine horn adhesion model. A single-dose of bevacizumab was effective in preventing postoperative intraperitoneal adhesion formation among 30 Wistar albino rats that underwent serosal injury by use of a standard technique after laparotomy with intraperitoneal bevacizumab.