Cystitis In Rats Research Articles

LncRNA MEG3 alleviates interstitial cystitis in rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway

PurposeInterstitial cystitis (IC), a chronic pain syndrome characterized by urinary frequency, urgency, and bladder or pelvic floor pain, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of long noncoding RNA Maternally Expressed Gene3 (lncRNA MEG3) in IC. MethodsAn IC rat model was established by intraperitoneal injection of cyclophosphamide combined with bladder perfusion of fisetin and tumor necrosis factor-α (TNF-α) to mimic IC. An in vitro model was established using TNF-α-induced rat bladder epithelium cells. H&E staining was used to assess bladder tissue damage and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine Nrf2, Bax, Bcl-2, cleaved caspase-3, p-p38, p38, p-NF-κB and NF-κB protein expression levels. RNA immunoprecipitation and RNA pull-down assays were used to examine the interaction between MEG3 and Nrf2. ResultsMEG3 levels were upregulated in IC tissues and bladder epithelial cells, whereas Nrf2 expression was found to be downregulated. Knockdown of MEG3 reduced bladder tissue injury, inflammation, oxidative stress and apoptosis. MEG3 was negatively correlated with Nrf2. Downregulation of MEG3 alleviated IC inflammation and injury by upregulating Nrf2 and inhibiting the p38/NF-κB pathway. ConclusionDownregulation of MEG3 alleviated inflammation and injury in IC rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.

Evaluation of the Efficacy of Lactobacillus acidophilus in the Treatment of Cyclophosphamide-induced Hemorrhagic Cystitis in Wistar Rats.

Hemorrhagic cystitis is an inflammatory complication that can be caused by the administration of cyclophosphamide, which is widely used as an antineoplastic agent. In the search for new therapeutic alternatives, probiotics can suppress the inflammatory process and, therefore, can be used to prevent this disease. Thus, this study aimed to evaluate the effects of using Lactobacillus acidophilus NCFM in the treatment of cyclophosphamide-induced hemorrhagic cystitis in Wistar rats. Lactobacillus acidophilus NCFM (2x108 CFU) was used in the treatment of cyclophosphamide- induced hemorrhagic cystitis (200 mg/kg, intraperitoneal) in 77 female Wistar rats. Rats were distributed into experimental groups (n = 9): control group (GC), zero control group (GCZ), inflammation group (GI), 24-hour acute treatment groups: 24-hour lactobacilli treatment group (GL24H) and mesna group (GM), and 30-day chronic treatment groups: lactobacilli treatment group (GTL) and mesna+lactobacilli group (GM+L). After treatment, animals were euthanized and biological materials were collected for blood count, biochemical analyses, examination of abnormal sediment elements (EAS), and histopathological analysis. GI results showed development of edema, macroscopic alterations, and signs of bleeding in the bladder; in addition, lesions in the urothelium and hemorrhage were also found. GL24H and GM presented intact urothelium, without inflammatory reaction and hematological or biochemical urine alterations. Therefore, this study demonstrated that L. acidophilus presented uroprotective effect against the action of cyclophosphamide in both the short and long term.

Intradetrusor plasmid VEGF165-gene therapy in treatment of cyclophosphamide induced cystitis in rats

Intradetrusor plasmid VEGF165-gene therapy in treatment of cyclophosphamide induced cystitis in rats

Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis

BackgroundCellular therapy seems to be an innovative therapeutic alternative for which mesenchymal stem cells (MSCs) have been shown to be effective for interstitial and hemorrhagic cystitis. However, the action of MSCs on chronic radiation cystitis (CRC) remains to be demonstrated. The aim of this study was to set up a rat model of CRC and to evaluate the efficacy of MSCs and their mode of action.MethodsCRC was induced by single-dose localized irradiation of the whole bladder using two beams guided by tomography in female Sprague–Dawley rat. A dose range of 20–80 Gy with follow-up 3–12 months after irradiation was used to characterize the dose effect and the kinetics of radiation cystitis in rats. For the treatment, the dose of 40 Gy was retained, and in order to potentiate the effect of the MSCs, MSCs were isolated from adipose tissue. After expansion, they were injected intravenously during the pre-chronic phase. Three injections of 5 million MSCs were administered every fortnight. Follow-up was performed for 12 months after irradiation.ResultsWe observed that the intensity and frequency of hematuria are proportional to the irradiation dose, with a threshold at 40 Gy and the appearance of bleeding from 100 days post-irradiation. The MSCs reduced vascular damage as well as damage to the bladder epithelium.ConclusionsThese results are in favor of MSCs acting to limit progression of the chronic phase of radiation cystitis. MSC treatment may afford real hope for all patients suffering from chronic radiation cystitis resistant to conventional treatments.

The Efficacy and Safety of a Human Perirenal Adipose Tissue-Derived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model

Background:Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients’ quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model.Methods:From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 μg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation.Results:The mean pain scores in the SVF 20 μl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group.Conclusion:This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.

Tropisetron Ameliorated Cyclophosphamide-Induced Hemorrhagic Cystitis via Restraining TLR-4/NF-κB and JAK1/STAT3 Signaling Pathways.

The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been corroborate to conduct a protective role in HC, but its specific etiology remains unclear. The objective of this research was to estimate the mechanism of action of Tropisetron in haemorrhagic cystitis tissue. Cyclophosphamide (CTX) was utilized to induce the construction of HC rat model, and rats were handled with different doses of Tropisetron. The impact of Tropisetron on the expression of inflammatory factors and oxidative stress factors in the rats with cystitis were measured by western blot, as well as the related proteins of toll-like receptor 4/nuclear transcription factor-κB (TLR-4/NF-κB) and januskinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways. CTX-induced cystitis in rats was accompanied by notable pathological tissue damage and increased bladder wet weight ratio, elevated mast cell numbers and collagen fibrosis compared to controls. Tropisetron ameliorated CTX-induced injury in a concentration-dependent manner. Futhermore, CTX induced oxidative stress and inflammatory damage, while Tropisetron can alleviate these injuries. Besides, Tropisetron ameliorated CTX-induced cystitis by restraining TLR-4/NF-κB and JAK1/STAT3 signalling pathways. Taken together, Tropisetron ameliorates cyclophosphamide-induced haemorrhagic cystitis via modulating TLR-4/NF-κB and JAK1/STAT3 signalling pathways. These findings carry important implication for the study of the molecular mechanisms of pharmacological treatment of hemorrhagic cystitis.

Effect of intravesical tarantula cubensis extract (Theranekron) on inflammation in an interstitial cystitis rat model

To reveal the histopathological and immunological outcomes of intravesical treatment with tarantula cubensis extract (TCE) in a rat model of interstitial cystitis. A total of 30 female Wistar albino rats were divided into three groups: group 1 (control group), group 2 (disease group), and group 3 (treatment group). The rat model of interstitial cystitis was created by biweekly intraperitoneal administration of cyclophosphamide (CYP). In group 3, TCE (a venom extracted from a brown spider known as tarantula cubensis) was administered intravesically after the model had been created. Urothelial degeneration, necrosis, ulcer, bleeding, edema, inflammation and mast cell count, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), myeloperoxidase (MPO), and hydroxyproline parameters were evaluated. Statistical analysis was performed using one-way analysis of variance, chi-square tests, and Kruskal-Wallis tests. All parameters were found to be lower in the rats in group 1 than in the other groups, and IL-6 and MPO values were found to be higher in group 2 (p < .001). The mean TNF-alpha value was highest in group 2 (p=.078). No difference was found between all groups regarding ulcer (p=.087). Urothelial degeneration, necrosis, edema, inflammation, hemorrhage and fibroblast proliferations, and hydroxyproline values were higher in group 3 (p < .001). Intravesical TCE instillation produces an anti-inflammatory effect by reducing the levels of inflammatory parameters such as IL-6, TNF-alpha, and MPO in bladder tissue. It also accelerates tissue healing by increasing hydroxyproline and fibroblast proliferation.

Changes in the Concentration of Extracellular DNA and Peripheral Blood Leukocytes in the Early Stages of Development of Radiation Cystitis in Rats

Changes in the Concentration of Extracellular DNA and Peripheral Blood Leukocytes in the Early Stages of Development of Radiation Cystitis in Rats

Effect of Simvastatin on Eosinophilic Inflammation of Bladder Tissue in Interstitial Cystitis Rat Model

In the urogenital system, simvastatin is associated with interstitial cystitis adverse effects, but the exact mechanism is not yet clearly defined. This study aims to determine the effect of simvastatin on eosinophilic inflammation of bladder tissue in vivo. Laboratory experimental research design with the post-test only control group using 24 female Wistar rats aged 8-10 weeks were randomly divided into simvastatin 50mg/kg BW (n=12) or placebo carboxymethylcellulose 0.5% (n=12). All groups received treatment through oral gavage for thirty days. After that, each group was divided equally into three subgroups: control rat, day 0 Interstitial Cystitis (IC) rat (IC0), and day 3 IC rat (IC3). Control or IC0 rats each received intravesical instillation of buffered saline or protamine sulfate (PS), respectively, and were terminated immediately less than 3 hours after instillation. The IC3 rats received intravesical PS instillation and were terminated three days post-instillation. The bladder tissue was made in Hematoxylin-Eosin histology preparations. As in previous studies, the results showed successful desquamation of the urothelium after PS instillation. Tissue eosinophil counts were significantly higher in the simvastatin group than in the placebo group in the IC3 model (15.50±5.92 vs. 4.00±2.83, p=0.013). It can be concluded that the mechanism of the adverse effect of simvastatin on bladder tissue is through increased tissue inflammation mediated by eosinophils along with urothelial layer destruction by the protamine sulfate.

Dehydrated Human Amnion-Chorion Membrane Extracts Can Ameliorate Interstitial Cystitis in Rats by Down-Regulating Inflammatory Cytokines and Protein Coding Genes: A Preclinical Study.

The study aimed to investigate the therapeutic impact of intravesical instillation of dehydrated human amnion-chorion membrane (HACM) extracts based on the primary pathological feature of interstitial cystitis (IC). We divided 15 female Sprague-Dawley rats into three groups: sham control, IC, and treatment group. IC was induced by 400-µL lipopolysaccharide (1 µg/µL), and it was replaced with normal saline in the sham control group. After IC induction, 300 µL dehydrated HACM extracts (3 mg/kg) were instilled into rats' urinary bladder weekly for 3 weeks. General histology, inflammatory cytokines, NF-κB, oxidative markers, and western blots results were examined. The urothelial denudation, mast-cell infiltration, and tissues fibrosis were all ameliorated. The elevated TNF-α, IL-1β, IL-6, IL-8, and NF-κB were all down-regulated by dehydrated HACM extracts (p &lt; 0.05). For reactive oxygen species, increased malondialdehyde, decreased superoxide dismutase, and decreased glutathione peroxidase were all reversed (p &lt; 0.05). In apoptosis of IC, elevated Bax and suppressed Bcl-2 were improved (p &lt; 0.05) after instillation. In fibrosis, dysregulated TGFβ/R-Smads/Snail was corrected by the instillation of dehydrated HACM (p &lt; 0.05). In conclusion, dehydrated HACM extracts could be a powerful remedy in treating IC by reconstructing the damaged urothelium, reducing mast-cell infiltration and inflammatory reactions, and ameliorating fibrotic changes.

Olmesartan ameliorates cyclophosphamide-induced hemorrhagic cystitis in rats via Nrf2/HO-1 signaling pathway

Hemorrhagic cystitis (HC) is considered a fatal complication of cyclophosphamide (CP). Down-regulation of Nrf2 and induction of pro-inflammatory mediators are the main pathological factors. Recently, ameliorative potential of the angiotensin II (AII) type-1 (AT1) receptor blocker olmesartan (OLM) on oxidative stress and inflammatory cytokines was reported. The current study aims to investigate the possible protective effect of OLM on CP-induced HC in Wistar rats. The animals were divided into the control group (0.5% W/V carboxymethylcellulose, p.o.); OLM group (20 mg/kg, p.o., for 21 days); CP group (a single dose of 100 mg/kg, i.p.); and the remaining groups that received CP i.p. with oral OLM 5, 10 and 20 mg/kg for 21 days, respectively. The bladder tissue was collected for histopathology, immunohistochemistry, ELISA, Western blot, and oxidative stress assay. The OLM at doses of 10 and 20 mg/kg attenuated increase in TNF-α, IL-6, NF-kB, iNOS, and COX-2 induced by CP. Additionally, it up-regulated the Nrf2/HO-1 pathway, bladder GSH content, and CAT and SOD activities. The data indicated that OLM inhibited ROS-induced NF-kB, which caused inhibition of pro-inflammatory cytokines and activation of the Nrf2/HO-1 pathway. Hence, OLM holds great promise for preventing CP-induced HC.

Simvastatin Toxicity Induces Alteration of Bladder Thickness in Interstitial Cystitis Rat Model

Background: Interstitial cystitis (IC) is a chronic inflammatory of the bladder, while statin can increase its risk.Recently, the exact mechanism is yet known. We hypothesizedsimvastatin can induce alteration of bladderthickness.Methods: Twenty-four female Wistar rats were aged 6-8 weeks old were divided into two groups and weretreated with simvastatin 50 mg/kg BW or carboxymethylcellulose 0.5% by oral gavage for 30 days. Each groupwas then equally subdivided into three groups: control, Interstitial Cystitis (IC) day-0, and IC day-3. Either ICor control rat group was induced by intravesical instillation of protamine sulfate or buffered saline respectively.All animals in the control and IC day-0 group were sacrificed and collected for the bladder tissue in less thanthree hours following intravesical treatment, while animals in the IC day-3 group three days after. All collectedtissue was prepared in hematoxylin-eosin staining and measured for the bladder thickness, namely the urothelial,suburothelial, and detrusor layer by image analyzer application.Results: There was no significant difference between the groups receiving simvastatin and placebo in thethickness of the urothelium, suburothelium, and detrusor layers in all rat models, both control, IC0, and IC3 rats(all p values &gt; 0.05). However, the thickness of the urothelium layer was consistently lower in the simvastatingroup than in the placebo group in all rat models.Conclusion: Mechanism of simvastatin toxicity on bladder tissue through urothelial denudation thus may alterthe urothelial barrier function.

Inhibition of U-II/UT signaling ameliorates cystitis-associated bladder hyperactivity by targeting the RhoA/Rho-kinase pathway.

Urotensin II (U-II) and its receptor (UT) are involved in the pathogenesis of various diseases; however, their association with the development of cystitis has not been elucidated. The present study was designed to investigate the functional role of U-II/UT signaling in cyclophosphamide (CYP)-induced cystitis. A total of 60 female rats were randomly divided into the control and CYP-treated groups. Intraperitoneal injection of CYP successfully induced cystitis in rats of the CYP-treated group. The protein and mRNA expression levels of U-II and UT were significantly enhanced in rat bladder tissues of the CYP-treated group. Furthermore, the results of the immunofluorescence staining analysis demonstrated that CYP treatment apparently increased the expression levels of UT in the urothelium layer, detrusor smooth muscle, and bladder interstitial Cajal-like cells. The selective antagonist of UT, SB657510 (10μm), significantly suppressed the CYP-induced increase in the spontaneous contractions of muscle strips and ameliorated the bladder hyperactivity of CYP-treated rats. Moreover, CYP treatment significantly increased the protein expression levels of Ras homolog family member (Rho) A and Rho-associated protein kinase 2 in rat bladder tissues. Following pretreatment with the Rho-kinase inhibitor Y-27632 (10μm), the inhibitory effects of SB657510 (10μm) on the spontaneous contractions of muscle strips were eliminated. In conclusion, the results of the present study suggested that activation of U-II/UT signaling promoted the development of cystitis-associated-bladder hyperactivity by targeting the RhoA/Rho-kinase pathway, indicating that the U-II/UT signaling could serve as a novel target for the treatment of interstitial cystitis/bladder pain syndrome.

Red propolis reduces inflammation in cyclophosphamide-induced hemorrhagic cystitis in rats.

Introduction. Cyclophosphamide (CP) is used to treat malignant neoplasias and control autoimmune diseases. Still, one of its metabolites, acrolein, is toxic to the urothelium and can lead to hemorrhagic cystitis and severe discomfort.Objective. To evaluate the ability of red propolis to prevent and treat CP-induced hemorrhagic cystitis in rats.Materials and methods. Red propolis was extracted in 1% gum arabic and administered subcutaneously (sc). In the first experiment, groups IA, IIA, and IIIA and groups IB, IIB, and IIIB received water, gum arabic (GA), or propolis, respectively, for 30 days. Then water (controls) or CP (treatment) was administered i.p. In the second experiment, groups IVA, VA, and VIA received water i.p. while groups IVB, VB, and VIB received CP i.p. This was followed by 5 injections at 2-hour intervals with either water, GA, or propolis. Bladder tissue was examined according to Gray’s criteria.Results. The total inflammatory histology score was significantly smaller in group VIB (11.33 ± 2.07). Mild inflammation predominated in group VIB while most of the animals in group IVB had severe inflammation (p=0.0375). Ulcers were predominantly multiple in Groups IVA and VB but rare or absent in Group VIB (p=0.0118). Urothelial cells were mostly absent in groups IVB and VB and present/normal in group VIB (p=0.0052). Fibrin was abundant in groups IVB and VA but mostly absent in group VIB (p=0.0273).Conclusions. Red propolis can reduce inflammation in CP-induced hemorrhagic cystitis in rats.

Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model.

The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason’s trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.

5-Aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis.

To investigate the effects of pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis in rats. Male Wistar rats (340-460 g) were pretreated with vehicle or with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (100/157 or 300/471 mg/kg/day, po) once daily for 7 days before cystometry. Saline or cyclophosphamide (150 mg/kg, ip) was administered 2 days before cystometry. Cystometry was performed under urethane anesthesia (0.8 g/kg, ip) via a catheter inserted into the bladder. After cystometry, bladder tissues were collected to perform hematoxylin and eosin staining for pathological evaluation (neutrophil infiltration, edema, and bleeding scores), and for enzyme-linked immunosorbent assay and real-time polymerase chain reaction for investigating tissue levels of myeloperoxidase, and mRNA levels of haem oxygenase-1 as a cytoprotective molecule. Compared to controls, cyclophosphamide induced a shorter intercontraction interval, lower bladder compliance, increased number of non-voiding contractions, and increased pathological scores and myeloperoxidase expression in the bladder. Pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (300/471 mg/kg/day) significantly improved cyclophosphamide-induced intercontraction interval shortening and increases in number of non-voiding contractions and neutrophil infiltration/bleeding scores and enhanced haem oxygenase-1 expression in the bladder. In addition, cyclophosphamide-induced decreases in bladder compliance and increases in myeloperoxidase were not detected with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate pretreatment. Pretreatment with 5-aminolevulinic acid expects protective effects on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis by improving inflammatory changes in bladder tissues perhaps via up-regulation of haem oxygenase-1.

Extracellular vesicles derived from mesenchymal stem cells alleviate neuroinflammation and mechanical allodynia in interstitial cystitis rats by inhibiting NLRP3 inflammasome activation

BackgroundNeuroinflammation in spinal dorsal horn (SDH) plays an important role in the pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exert potent anti-inflammatory activities in the treatment of various diseases. This study aimed to determine the therapeutic effects of MSC-EVs on IC and furtherly investigate the potential mechanism to attenuate neuroinflammation.MethodsFemale IC rat model was established by intraperitoneal injection of cyclophosphamide (50 mg/kg, every 3 days for 3 doses). Inhibition of NLRP3 inflammasome was performed by intraperitoneal injection of MCC950 (10 mg/kg). MSC-EVs were isolated from the culture supernatants of human umbilical cord derived MSCs using ultracentrifugation, and then injected intrathecally into IC rats (20 μg in 10 μl PBS, every other day for 3 doses). Suprapubic mechanical allodynia was assessed using up-down method with von Frey filaments, and micturition frequency was examined by urodynamics. The expression of NLRP3 inflammasome components (NLRP3 and Caspase-1), glial cell markers (IBA-1 and GFAP), proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-18) and TLR4/NF-κB signal pathway (TLR4, p65 NK-κB and phospho-p65 NK-κB) in L6–S1 SDH was measured by Western blot analysis. The cellular localization of NLRP3 in SDH was detected using immunofluorescence co-staining.ResultsNLRP3 inflammasome was activated in neurons in SDH of IC rats. NLRP3 inflammasome activation contributed to activation of glial cells and process of spinal neuroinflammation in IC rats, and was related to suprapubic mechanical allodynia and frequent micturition. Intrathecal injection of MSC-EVs alleviated suprapubic mechanical allodynia and frequent micturition in IC rats, restrained activation of glial cells and attenuated neuroinflammation in SDH. In addition, MSC-EV treatment significantly inhibited activation of both NLRP3 inflammasomes and TLR4/NF-κB signal pathway.ConclusionsNLRP3 inflammasome activation is involved in the neuroinflammation of IC. Intrathecal injection of MSC-EVs alleviates neuroinflammation and mechanical allodynia in IC by inhibiting the activation of NLRP3 inflammasome, and TLR4/NF-κB signal pathway may be the potential regulatory target.

Effect of the neuropathic pain receptor P2X3 on bladder function induced by intraperitoneal injection of cyclophosphamide (CYP) in interstitial cystitis rats.

BackgroundThe role of purinergic receptor P2X3 in pathological bladder dysfunction and chronic pelvic pain remains unclear. We aim to investigate the effect of P2X3 on bladder function in interstitial cystitis (IC) through the IC rat model induced by cyclophosphamide (CYP).MethodsA total of 120 female Sprague-Dawley (SD) rats were randomly divided into 6 groups: control, CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups. The control group was injected with normal saline. The rats in the CYP-4h and CYP-48h groups were given a single high dose. The rats in the CYP-10d, CYP-30d, and CYP-45d groups were given a low dose of CYP repeatedly every three days. Bladder voiding function was measured using urodynamic techniques to observe the effect of the P2X3 receptor on bladder function in CYP-induced IC.ResultsThe rats in the CYP-4h group showed significant overactivity of the bladder compared with the control group, the bladder voiding interval was shortened (P<0.01), and the maximal voiding pressure was increased (P<0.01). At the same time, the degree of overactive bladder in the CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups became increasingly serious, the interval of bladder micturition was shortened stepwise (P<0.01), and the maximal micturition pressure was increased stepwise (P<0.01). Compared with the control group, the CYP-48h group mainly showed a shorter bladder voiding interval (P<0.01), lower voiding volume, and higher activation of mast cells and inflammatory factors in the bladder. In the CYP-10d group, bladder mast cell activation and inflammatory factors increased significantly. Intrathecal injection (IT) of A-317491 significantly prolonged the bladder voiding intervals in CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d rats (P<0.01), and the maximal voiding pressure of the CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups was significantly decreased (P<0.05), while the maximal voiding pressure of the CYP-10d group was not significantly affected.ConclusionsP2X3 receptors in dorsal root ganglion (DRG) play an important role in bladder function induced by intraperitoneal injection of CYP in rats. IT of P2X3 inhibitors can significantly improve the grade of bladder voiding dysfunction and chronic pelvic pain.

A0029 - Dehydrated human amnion-chorion membranes can ameliorate interstitial cystitis in rats by down-regulating inflammatory cytokines and protein coding genes

A0029 - Dehydrated human amnion-chorion membranes can ameliorate interstitial cystitis in rats by down-regulating inflammatory cytokines and protein coding genes

Tumor protein P63 Regulated 1 contributes to inflammation and cell proliferation of cystitis glandularis through regulating the NF-кB/cyclooxygenase-2/prostaglandin E2 axis.

Cystitis glandularis is characterized by chronic inflammation and hyperproliferation of the bladder mucosa, and it contributes to the progression of bladder adenocarcinoma. Tumor Protein P63 Regulated 1 (TPRG1) is related to cellular inflammatory response, and dysregulation of TPRG1 in tumor tissues is associated with tumor recurrence. The effect of TPRG1 on cystitis glandularis was investigated in this study. Firstly, bladder specimens were isolated from patients with cystitis glandularis and Escherichia coli-induced cystitis rat. Expression of TPRG1 was found to be up-regulated in the bladder specimen. Moreover, adeno-associated virus (AAV)-mediated silencing of TPRG1 was injected into rat, and data from hematoxylin and eosin (H & E) staining showed that injection with AAV-shTPRG1 ameliorated E. coli-induced histological changes in bladder tissues of rats and suppressed the inflammatory response. Secondly, TPRG1 was also increased in primary cystitis glandularis cells. Knockdown of TPRG1 decreased cell proliferation and suppressed the migration of primary cystitis glandularis cells. Thirdly, cyclooxygenase-2 (COX-2) was up-regulated in the bladder specimens isolated from patients with cystitis glandularis and E. coli-induced cystitis rat. Injection with AAV-shTPRG1 reduced protein expression of COX-2, p65 and prostaglandin E2 (PGE2) in the bladder specimen. Finally, interference of COX-2 attenuated TPRG1 over-expression-induced increase in cell proliferation and migration in the primary cystitis glandularis cells. In conclusion, TPRG1 promoted inflammation and cell proliferation of cystitis glandularis through activation of NF-КB/COX2/PGE2 axis.