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吡格列酮对海绵体神经损伤大鼠模型勃起功能恢复的疗效。

Efficacy of pioglitazone on erectile function recovery in a rat model of cavernous nerve injury.

作者信息

Aliperti Louis A, Lasker George F, Hagan Sharika S, Hellstrom Joshua A, Gokce Ahmet, Trost Landon W, Kadowitz Philip J, Sikka Suresh C, Hellstrom Wayne J G

机构信息

Department of Urology, Tulane University Medical Center, New Orleans, LA.

Department of Urology, Sakarya University School of Medicine, Sakarya, Turkey.

出版信息

Urology. 2014 Nov;84(5):1122-7. doi: 10.1016/j.urology.2014.07.033. Epub 2014 Oct 24.

Abstract

OBJECTIVE

To examine the effect of pioglitazone on erectile function in a rat model of postprostatectomy erectile dysfunction.

METHODS

Twenty adult rats were divided into 4 groups: (a) sham, (b) control--bilateral cavernosal nerve crush injury (BCNI), (c) BCNI + low-dose pioglitazone (PioL), and (d) BCNI + high-dose pioglitazone (PioH). Sham and control rats were administered phosphate-buffered saline, whereas PioL and PioH rats received 0.65 and 6.5 mg/kg of pioglitazone, respectively. All treatments were administered by oral gavage for 14 days. After treatment, animals underwent surgery for endpoint cavernosal response to define hemodynamic parameters of erectile function, reported as the ratio of intracavernosal pressure to mean arterial pressure. Corporal tissue was retrieved for histologic and molecular analysis.

RESULTS

Animals treated with pioglitazone experienced dose-dependent improvements in the ratio of intracavernosal pressure to mean arterial pressure, with the PioH group achieving results similar to the sham group: sham, 0.774; BCNI, 0.421; PioL, 0.616; PioH, 0.758 (P = .0006). PioH animals demonstrated increased expression of endothelial nitric oxide (eNOS) and neuronal nitric oxide (nNOS), whereas both PioL and PioH animals had increased staining for anti--smooth muscle actin antibody and nonsignificant increases in cyclic guanosine monophosphate (cGMP).

CONCLUSION

Pioglitazone improves erectile function in rats undergoing BCNI via a nitric oxide--mediated pathway.

摘要

目的

研究吡格列酮对前列腺切除术后勃起功能障碍大鼠模型勃起功能的影响。

方法

将20只成年大鼠分为4组:(a)假手术组,(b)对照组——双侧海绵体神经挤压伤(BCNI)组,(c)BCNI+低剂量吡格列酮(PioL)组,(d)BCNI+高剂量吡格列酮(PioH)组。假手术组和对照组大鼠给予磷酸盐缓冲盐水,而PioL组和PioH组大鼠分别接受0.65和6.5mg/kg的吡格列酮。所有处理均通过灌胃给药14天。处理后,动物接受手术以确定海绵体对终点刺激的反应,以定义勃起功能的血流动力学参数,以海绵体内压与平均动脉压的比值表示。取出阴茎海绵体组织进行组织学和分子分析。

结果

接受吡格列酮治疗的动物海绵体内压与平均动脉压的比值呈剂量依赖性改善,PioH组的结果与假手术组相似:假手术组为0.774;BCNI组为0.421;PioL组为0.616;PioH组为0.758(P = 0.0006)。PioH组动物内皮型一氧化氮合酶(eNOS)和神经元型一氧化氮合酶(nNOS)的表达增加,而PioL组和PioH组动物抗平滑肌肌动蛋白抗体染色均增加,环磷酸鸟苷(cGMP)无明显增加。

结论

吡格列酮通过一氧化氮介导的途径改善BCNI大鼠的勃起功能。

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