Klutke John, Ji Qing, Campeau Joseph, Starcher Barry, Felix Juan Carlos, Stanczyk Frank Z, Klutke Carl
Department of Obstetrics and Gynecology, USC-Keck School of Medicine, Women's and Children's Hospital, Los Angeles, CA 90033, USA.
Acta Obstet Gynecol Scand. 2008;87(1):111-5. doi: 10.1080/00016340701819247.
Genital prolapse is a debilitating manifestation of pelvic floor dysfunction. The cause of this condition has not been elucidated. The purpose of this study was to determine elastin content and RNA expression of related enzymes of elastin synthesis in uterosacral ligament biopsies from women with severe prolapse, and controls with normal pelvic support.
Biopsies were taken from the uterosacral ligament tissue of 31 women with Grade III or greater prolapse and 29 women with normal pelvic support. Elastin content was assessed by measuring desmosine using radioimmunoassay, and quantitative real time PCR was performed to quantify mRNA levels of lysyl oxidase (LOX), lysyl oxidase like-1 (LOXL1), LOXL2 and fibulin-5 (FIB-5).
The mean desmosine concentration found in uterosacral ligaments of women with prolapse (n =26) was 103.3+/-59.3 pmolD/mgP compared to controls (n =29) 120.5+/-47.4 pmolD/mgP (p =0.1943). In the subgroup of subjects with complete procidentia (n =8), mean desmosine concentration was 50.6+/-25.8 and 127.1+/-42.2 pmolD/mgP in age-matched controls (n =12) (p <0.05). In tissue from subjects with more than 2 vaginal deliveries (n =18), the mean desmosine concentration was 99.9+/-60.7 and 133.0+/-44.0 pmolD/mgP in controls (n =17) (p <0.05). Expression of LOX, LOXL1 and LOXL2 decreased 8.2-fold+/-3.4, 5.0-fold+/-1.7 and 15.2-fold+/-5.2, respectively (mean+/-SD) in cases versus controls (p<0.05). Expression of FIB-5 was increased 3.1-fold+/-0.7 compared to controls (p<0.05).
Significantly decreased desmosine content was measured in the uterosacral ligament tissue from women with prolapse versus controls in women with parity >2 and in women with complete procidentia. Suppression of mRNA for LOX and two LOX isoenzymes was correspondingly present. These results suggest that altered elastin metabolism is present in women with uterine prolapse.
生殖器脱垂是盆底功能障碍的一种使人衰弱的表现。这种疾病的病因尚未阐明。本研究的目的是确定重度脱垂女性和盆底支持正常女性的子宫骶韧带活检组织中弹性蛋白含量以及弹性蛋白合成相关酶的RNA表达。
从31例III度及以上脱垂女性和29例盆底支持正常的女性的子宫骶韧带组织中获取活检样本。通过放射免疫分析法测量锁链素评估弹性蛋白含量,并进行定量实时PCR以量化赖氨酰氧化酶(LOX)、赖氨酰氧化酶样-1(LOXL1)、LOXL2和纤连蛋白-5(FIB-5)的mRNA水平。
脱垂女性(n = 26)子宫骶韧带中锁链素的平均浓度为103.3±59.3 pmolD/mgP,而对照组(n = 29)为120.5±47.4 pmolD/mgP(p = 0.1943)。在完全子宫脱垂的亚组(n = 8)中,年龄匹配的对照组(n = 12)中锁链素的平均浓度分别为50.6±25.8和127.1±42.2 pmolD/mgP(p < 0.05)。在有超过2次阴道分娩史的受试者(n = 18)的组织中,对照组(n = 17)中锁链素的平均浓度分别为99.9±60.7和133.0±44.0 pmolD/mgP(p < 0.05)。与对照组相比,病例组中LOX、LOXL1和LOXL2的表达分别下降了8.2倍±3.4、5.0倍±1.7和15.2倍±5.2(平均值±标准差)(p<0.05)。与对照组相比,FIB-5的表达增加了3.1倍±0.7(p<0.05)。
与对照组相比,有超过2次分娩史的脱垂女性和完全子宫脱垂女性的子宫骶韧带组织中锁链素含量显著降低。相应地存在LOX和两种LOX同工酶mRNA的抑制。这些结果表明子宫脱垂女性存在弹性蛋白代谢改变。