Scholarlink

Introduction and Hypothesis <p>Increased nerve growth factor (NGF) expression in the bladder is known to contribute to the hyperexcitability of C-fiber bladder afferent pathways in interstitial cystitis/painful bladder syndrome (IC/PBS). We hypothesized that intravesical administration of vivo-morpholino NGF antisense oligonucleotide (OND) would downregulate NGF expression and alleviate IC/PBS-associated urinary frequency.</p> Methods <p>Eighteen virgin female rats were randomly divided into three groups: (1) saline-injected control, (2) cyclophosphamide (CYP) plus intravesical instillation with normal saline, and (3) CYP plus intravesical instillation with vivo-morpholino NGF antisense OND (2&#xa0;mg/kg). Female rats received an intravesical instillation of vivo-morpholino NGF antisense oligonucleotide once daily for three consecutive days, with a 30-min dwell time. Cystometric and histological evaluations were performed 24&#xa0;h after the last instillation. Cystometry was used to evaluate voiding interval values under anesthesia, while NGF expression was measured.</p> Results <p>Immunohistochemistry demonstrated a ~ 26% increase in bladder NGF expression in CYP-induced IC/PBS rats compared with controls, particularly in the urothelium and suburothelium, whereas intravesical NGF antisense therapy reduced NGF levels by ~ 28%, approaching control values. Cystometric analysis revealed that CYP treatment reduced voiding intervals by ~ 61% at 24&#xa0;h and ~ 40% at 48&#xa0;h compared to controls, consistent with bladder overactivity. NGF antisense therapy markedly prolonged voiding intervals, increasing them by ~ 113% at 24&#xa0;h and ~ 80% at 48&#xa0;h compared with CYP, indicating progressive functional improvement. Baseline and maximal bladder pressures were not significantly different among groups.</p> Conclusions <p>Intravesical administration of vivo-morpholino NGF antisense OND significantly prolonged voiding intervals and attenuated bladder NGF expression in CYP-induced acute IC/PBS female rats. These results highlight the potential of NGF antisense OND as a novel intravesical therapy for IC/PBS.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Intravesical Instillation with Vivo-Morpholino Nerve Growth Factor Antisense Therapy Ameliorates Acute Interstitial Cystitis/Painful Bladder Syndrome-Related Urinary Frequency in a Rat Model

  • 期刊论文

  • 发表日期：

    2025年10月25日

查看全文
  • Yung-Hsiang Chen,
  • Wen-Chi Chen,
  • Po-Len Liu,
  • Huey-Yi Chen

摘要

Introduction and Hypothesis

Increased nerve growth factor (NGF) expression in the bladder is known to contribute to the hyperexcitability of C-fiber bladder afferent pathways in interstitial cystitis/painful bladder syndrome (IC/PBS). We hypothesized that intravesical administration of vivo-morpholino NGF antisense oligonucleotide (OND) would downregulate NGF expression and alleviate IC/PBS-associated urinary frequency.

Methods

Eighteen virgin female rats were randomly divided into three groups: (1) saline-injected control, (2) cyclophosphamide (CYP) plus intravesical instillation with normal saline, and (3) CYP plus intravesical instillation with vivo-morpholino NGF antisense OND (2 mg/kg). Female rats received an intravesical instillation of vivo-morpholino NGF antisense oligonucleotide once daily for three consecutive days, with a 30-min dwell time. Cystometric and histological evaluations were performed 24 h after the last instillation. Cystometry was used to evaluate voiding interval values under anesthesia, while NGF expression was measured.

Results

Immunohistochemistry demonstrated a ~ 26% increase in bladder NGF expression in CYP-induced IC/PBS rats compared with controls, particularly in the urothelium and suburothelium, whereas intravesical NGF antisense therapy reduced NGF levels by ~ 28%, approaching control values. Cystometric analysis revealed that CYP treatment reduced voiding intervals by ~ 61% at 24 h and ~ 40% at 48 h compared to controls, consistent with bladder overactivity. NGF antisense therapy markedly prolonged voiding intervals, increasing them by ~ 113% at 24 h and ~ 80% at 48 h compared with CYP, indicating progressive functional improvement. Baseline and maximal bladder pressures were not significantly different among groups.

Conclusions

Intravesical administration of vivo-morpholino NGF antisense OND significantly prolonged voiding intervals and attenuated bladder NGF expression in CYP-induced acute IC/PBS female rats. These results highlight the potential of NGF antisense OND as a novel intravesical therapy for IC/PBS.