Apoptosis in the rat penis after penile denervation
Apoptosis in the rat penis after penile denervation
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DOI：
10.1016/s0022-5347(01)64572-5
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发表时间：
1997-08-01
影响因子：
6.6
通讯作者：
Shabsigh, R
中科院分区：
文献类型：
--
作者：
Klein, LT;Miller, MI;Shabsigh, R
目的：尽管保留神经的前列腺癌切除术取得了进展，但有些患者会出现阳痿或主观抱怨阴茎尺寸缩小。我们假设这些临床观察结果可能是由于海绵体神经损伤导致阴茎内细胞程序性死亡（凋亡）。我们利用大鼠模型的阴茎去神经支配，以证明细胞凋亡后denervation.Methods和材料：15只雄性Sprague道利大鼠进行腹部探查和双侧海绵体神经切断术。15例假手术作为正常对照。分别于术后第1、2、3、6、10天处死大鼠，取阴茎。提取信使RNA并在北方印迹上探测硫酸化糖蛋白-2（SGP-2）。SGP-2是据报道在凋亡组织中升高的基因产物。使用单独的去神经和假手术大鼠进行DNA提取（术后第2天处死），以证明在凋亡组织中发现的核小体间DNA片段化（梯状）。结果：北方印迹分析显示，去神经支配组SGP-2 mRNA表达明显增加，而假手术组SGP-2 mRNA表达明显减少。DNA提取研究显示，在去神经支配组中存在琼脂糖凝胶上的核小体间DNA片段（细胞凋亡的标志物），而在假手术大鼠中存在完整的高分子量DNA。结论：大鼠阴茎失神经支配后，阴茎勃起组织发生了细胞凋亡。这在以前的文献中没有描述过，可能在分子水平上提供一些关于根治性阴茎切除术后阳痿和/或阴茎尺寸减小的机制的解释。
Purpose: Despite the advances in nerve sparing prostatectomy for prostate cancer, some patients develop impotence or subjectively complain of a decrease in penile size. We hypothesized that these clinical observations may be explained by injury to the cavernous nerves resulting in programmed cell death (apoptosis) within the penis. We utilized a rat model of penile denervation in order to demonstrate apoptosis after denervation.Methods and Materials: Fifteen male Sprague Dawley rats underwent abdominal exploration and bilateral cavernous neurotomy. Fifteen sham operations were performed as normal controls. The rats were sacrificed on postoperative day 1, 2, 3, 6, and 10 and their penises were harvested. Messenger RNA was extracted and probed on a northern blot for sulfated glycoprotein-2 (SGP-2). SGP-2 is a gene product reported to be elevated in apoptotic tissues. Separate denervated and sham rats were used for DNA extraction (sacrificed postoperative day #2) in order to demonstrate the internucleosomal DNA fragmentation (laddering) found in apoptotic tissues. In addition, in situ histology was performed with ISEL techniques (in situ end labelling) to stain for apoptotic nuclei in denervated rats.Results: Northern blot analysis showed a large increase in SGP-2 mRNA expression in the denervated rats with little detected in the sham operated group. DNA extraction studies revealed the presence of internucleosomal DNA fragmentation on agarose gel (a marker for apoptosis) in the denervated group versus intact high molecular weight DNA in the sham rats. In addition, in situ staining of denervated penile erectile tissue demonstrated apoptotic nuclei in the cavernous tissue.Conclusion: Apoptosis of penile erectile tissue occurs after denervation of the rat penis. This has not been previously described in the literature and may offer some explanation at the molecular level concerning the mechanism of impotence and/or decrease in penile size after radical prostatectomy.