氧化应激和线粒体凋亡参与盆腔器官脱垂的发病机制。
Involvement of oxidative stress and mitochondrial apoptosis in the pathogenesis of pelvic organ prolapse.
机构信息
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
出版信息
J Urol. 2013 Feb;189(2):588-94. doi: 10.1016/j.juro.2012.09.041. Epub 2012 Dec 20.
PURPOSE
Biomechanical weakness of the pelvic supportive structures has been proposed to be a cause of pelvic organ prolapse. However, the molecular mechanism involved in these changes is not completely understood. In this investigation we evaluated oxidative stress biomarkers in the uterosacral ligaments of women with pelvic organ prolapse and compared them with those of women with normal support. In addition, mitochondrial apoptosis was examined.
MATERIALS AND METHODS
Samples were collected from 26 women with advanced stage pelvic organ prolapse and 29 age matched controls. The expression levels of 8-OHdG and 4-hydroxy-2-nonenal in the uterosacral ligaments were measured using immunohistochemistry. To assess mitochondrial apoptosis we performed TUNEL assay, immunohistochemistry for cleaved caspase-3 and cytochrome c, and Western blot analyses for cleaved caspase-3 and caspase-9.
RESULTS
The mean percentage of cells immunopositive for 8-OHdG, 4-hydroxy-2-nonenal, TUNEL, cleaved caspase-3 and cytochrome c in the uterosacral ligaments was significantly higher in patients with pelvic organ prolapse than in controls. Similarly, Western blot analysis revealed increased expression of cleaved caspase-3 and caspase-9 in patients with pelvic organ prolapse. Correlation analyses revealed significant positive correlations between the percentage of cells immunopositive for 8-OHdG or 4-hydroxy-2-nonenal and markers of mitochondrial apoptosis. Analyzing by pelvic organ prolapse quantification system stage according to C point, the mean percentage of cells immunopositive for 8-OHdG, 4-hydroxy-2-nonenal and cytochrome c was significantly higher in patients with pelvic organ prolapse compared to controls, regardless of stage. However, the mean percentage of TUNEL and cleaved caspase-3 positive cells was significantly higher only in patients with stage III or IV pelvic organ prolapse.
CONCLUSIONS
Oxidative stress and increased mitochondrial apoptosis may contribute to the pathological process of pelvic organ prolapse.
目的
盆腔支持结构的生物力学弱点被认为是盆腔器官脱垂的原因。然而，涉及这些变化的分子机制尚不完全清楚。在这项研究中，我们评估了患有盆腔器官脱垂的女性的子宫骶骨韧带中的氧化应激生物标志物，并将其与具有正常支撑的女性进行了比较。此外，还检查了线粒体凋亡。
材料和方法
从 26 名患有晚期盆腔器官脱垂的女性和 29 名年龄匹配的对照者中采集样本。使用免疫组织化学法测量子宫骶骨韧带中 8-OHdG 和 4-羟基-2-壬烯醛的表达水平。为了评估线粒体凋亡，我们进行了 TUNEL 测定、cleaved caspase-3 和细胞色素 c 的免疫组织化学分析以及 cleaved caspase-3 和 caspase-9 的 Western blot 分析。
结果
患有盆腔器官脱垂的患者子宫骶骨韧带中 8-OHdG、4-羟基-2-壬烯醛、TUNEL、cleaved caspase-3 和细胞色素 c 免疫阳性细胞的平均百分比明显高于对照组。同样，Western blot 分析显示患有盆腔器官脱垂的患者 cleaved caspase-3 和 caspase-9 的表达增加。相关性分析显示，8-OHdG 或 4-羟基-2-壬烯醛免疫阳性细胞的百分比与线粒体凋亡标志物之间存在显著正相关。根据 C 点按盆腔器官脱垂定量系统分期进行分析，患有盆腔器官脱垂的患者的 8-OHdG、4-羟基-2-壬烯醛和细胞色素 c 免疫阳性细胞的平均百分比明显高于对照组，无论分期如何。然而，TUNEL 和 cleaved caspase-3 阳性细胞的平均百分比仅在患有 III 或 IV 期盆腔器官脱垂的患者中显著升高。
结论
氧化应激和增加的线粒体凋亡可能导致盆腔器官脱垂的病理过程。
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