Division of Urogynecology and Pelvic Reconstructive Surgery, Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
Division of Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.
Investig Clin Urol. 2018 Jul;59(4):257-262. doi: 10.4111/icu.2018.59.4.257. Epub 2018 Jun 15.
To understand the therapeutic potential of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist with a propensity to cause bladder mucosal proliferation, on interstitial cystitis (IC) in a rat model.
Using a previously described animal model for IC, Sprague-Dawley rats were treated with biweekly cyclophosphamide injections (35 mg/kg) to induce cystitis. Animals were divided into 4 groups (n=6 for each group): IC plus daily sham saline gavage (ICPio), IC plus daily pioglitazone gavage (15 mg/kg) (ICPio), normal rats with daily pioglitazone (ICPio), and normal rats with neither IC nor pioglitazone (ICPio or Control). At the end of four weeks, urinary frequency and bladder capacity were measured. Histologic examination of urothelial integrity was also performed.
Average voids per hour were significantly lower in ICPio (4.0±1.9) vs. ICPio (10.0±2.4) rats (p<0.01) and were similar to ICPio (6.0±1.4) and ICPio (6.0±1.5) controls. Cystometric capacity was significantly higher in ICPio (0.945±0.122 mL) vs. ICPio rats (0.588±0.165 mL, p=0.01) and was comparable to ICPio capacity (0.817±0.196 mL) and ICPio capacity (0.941±0.188 mL). Urothelial structural integrity was improved in ICPio rats versus ICPio rats upon histologic observation.
Pioglitazone, a PPAR-γ agonist, improved bladder function in cyclophosphamide-induced cystitis by both observed urinary frequency and measured cystometric capacity. Urothelial structural integrity was also improved. Pioglitazone, due to a propensity to cause bladder mucosal proliferation, may prove useful for treating IC, and deserves further investigation.
了解吡格列酮（一种过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂，具有引起膀胱黏膜增殖的倾向）在大鼠模型中对间质性膀胱炎（IC）的治疗潜力。
使用先前描述的 IC 动物模型，对 Sprague-Dawley 大鼠进行两周一次的环磷酰胺注射（35mg/kg）以诱导膀胱炎。将动物分为 4 组（每组 6 只）：IC 加每日假盐水灌胃（ICPio）、IC 加每日吡格列酮灌胃（15mg/kg）（ICPio）、每日给予吡格列酮的正常大鼠（ICPio）和既无 IC 也无吡格列酮的正常大鼠（ICPio 或对照）。四周结束时，测量排尿频率和膀胱容量。还进行了尿路上皮完整性的组织学检查。
ICPio 大鼠的平均每小时排尿次数（4.0±1.9）明显低于 ICPio 大鼠（10.0±2.4）（p<0.01），与 ICPio 和 ICPio 对照组（6.0±1.4）和 ICPio 对照组（6.0±1.5）相似。ICPio 大鼠的膀胱容量（0.945±0.122mL）明显高于 ICPio 大鼠（0.588±0.165mL，p=0.01），与 ICPio 容量（0.817±0.196mL）和 ICPio 容量（0.941±0.188mL）相当。组织学观察显示，吡格列酮治疗组大鼠的尿路上皮结构完整性得到改善。
吡格列酮是一种 PPAR-γ 激动剂，通过观察到的排尿频率和测量的膀胱容量，改善了环磷酰胺诱导的膀胱炎中的膀胱功能。尿路上皮结构完整性也得到了改善。由于吡格列酮具有引起膀胱黏膜增殖的倾向，因此它可能对治疗 IC 有用，值得进一步研究。
