Identifying the clinical presentations, progression, and sequela of pelvic inflammatory disease through physiological, histological and ultrastructural evaluation of a rat animal model

Abstract

Background: Patients with pelvic inflammatory disease (PID) are at an increased risk of ectopic pregnancy, infertility, and varying degrees of chronic pelvic pain. The aims of this study were to establish a rat model of PID and characterize its progression in order to assist in the study of pathophysiological mechanisms and to provide animal model for future studies of PID treatments.Methods: Fifty Sprague-Dawley rats (female, 6-weeks-old) were divided into a model group (n=28) and a control group (n=22). The rat endometrium was mechanically injured by a needle which moved back and forth 3 times on the endometrial tissue, and a mixed bacterial solution (6×10 8 CFU) of equal concentrations of Escherichia coli and Staphylococcus aureus was injected into both horns of the rat uterus. Physiological characteristics including weight, temperature, blood, and inflammatory factors were compared, and immunohistochemistry and transmission electron microscopy were used to evaluate the progress and sequela of PID. Results:The model rats experienced acute PID in the first 14 days and exhibited higher body temperatures and decreased body weight. Infection-related factors in the blood were also significantly changed compared with the normal group, with obviously increased serum levels of C-reactive protein (CRP), interferon gamma (IFN-γ), and interleukin-4 (IL-4). Congestion and edema were observed in the uteri of the model rats, followed by infiltration of numerous inflammatory cells and ultrastructural morphology changes.Histological examination of the uterus showed that adhesion initially appeared at approximately 21 days.In addition to the increased collagen fibers biomass, the expression of transforming growth factor-beta 1 (TGF-β1) was elevated, which might have contributed to pelvic tissue adhesion formation in the PID sequela.Conclusions: This study clearly described the characteristics and progression of PID in a rat model. The detailed evidence increased our understanding of the pathogenesis and progression of PID and may be useful for future studies of PID treatments.

Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats

“…We also monitored white blood cell (WBC) counts in the blood, which is an indicator of infection-related inflammation. Previous study showed a temporary decrease in WBC in PID model group rats at the beginning of 0–2 days, which might be caused by the severe infection in PID rats ( Fan et al, 2021 ). The WBC count in the PID model group remained elevated until D7 and then began to decline, but it was still at a high level.…”

“…According to our previous study, PID model rats experience a 14- to 21-day period of acute inflammation, with the degree of inflammation being the highest at 6–8 days, followed by a period of chronic inflammation and sequelae with adhesion ( Fan et al, 2021 ). The day of model establishment was considered D-3, drug was administered from D0 to D14, and samples were collected on D3, D14, and D49 ( Figure 1A ).…”

“…Infection results in fibrinous or suppurative inflammatory damage along the epithelial surface of the uterine and the peritoneal surface of the fallopian tubes and ovaries, which leads to scarring, adhesions, and possibly partial or total obstruction of the uterine ( Brotman, 2011 ). Previous studies have reported that uterine tissue adhesions can be observed pathologically after only 14 days of pelvic infection ( Fan et al, 2021 ). However, treatment with levofloxacin or KFXYS for 14 days had a certain effect on reducing the adhesion area, the combination treatment was the most effective in protecting the uterine mucous membrane from inflammatory adhesion and reducing the adhesion area in the uterine mucosa.…”

“…Suitable mice were randomly allocated into a sham operation group ( n = 15) and an experimental PID model group ( n = 60). A mouse model of PID was established as we previously reported ( Fan et al, 2021 ). Briefly, the rats were fasted overnight and then anesthetized with an intraperitoneal injection of 1% pentobarbital sodium (30 mg/kg).…”

“…Multiple pathogens and multiple infections can enhance inflammation of the upper genital tract, and a rat model of PID reflecting this phenomenon was previously established in our previous research ( Fan et al, 2021 ). In this study, we observed that KFXYS alone or together with antibiotics alleviated PID in rats.…”