盆底器官脱垂妇女阴道前壁Ⅰ、Ⅲ型胶原及代谢变化的研究
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摘要
目的
     通过对盆底器官脱垂(pelvic organ prolapse,POP)妇女阴道前壁组织中Ⅰ、Ⅲ型胶原含量及其代谢标志物(Ⅰ型前胶原羧基末端前肽,PⅠCP;Ⅰ型胶原交联羧基末端肽,ICTP;Ⅲ型前胶原氨基末端肽,PⅢNP)水平的检测及其相关性的研究;阐述POP患者阴道前壁组织的胶原代谢所发生的改变,以分析Ⅰ、Ⅲ型胶原代谢变化与POP发生的关系。
     方法
     收集在我院妇产科行阴道前壁修补术患者的阴道前壁组织,予匀浆后,应用酶联免疫吸附法(ELISA)检测绝经前POP组(16例)、绝经前对照组(19例)、绝经后POP组(18例)、绝经后对照组(10例)共4组63例患者阴道前壁组织中Ⅰ、Ⅲ型胶原含量及其二者代谢标志性产物PⅠCP、ICTP及PⅢNP的含量水平。
     结果
     1.绝经后POP组和绝经后对照组在年龄方面高于绝经前POP组和绝经前对照(P<0.05),余产次、体重指数等一般情况在各组间均无明显差异(P>0.05)。
     2.绝经前POP组及绝经后POP组患者阴道前壁组织中Ⅰ型胶原含量均明显低于相应对照组(P<0.05),其降低幅度分别为21.3%和24.1%。
     3.绝经前后POP组患者阴道前壁组织中PⅠCP平均水平较对应的对照组稍高,但二者无明显差异(P>0.05);绝经前组组织ICTP含量明显高于绝经前对照组(P<0.05),绝经后POP患者较绝经后对照组亦明显升高(P<0.05)。
     4.绝经前POP组与绝经后POP组妇女阴道前壁组织中Ⅲ型胶原含量均较相应对照组显著降低(P<0.05),其降低幅度分别为29.70%和29.18%。
     5.绝经前及绝经后POP妇女阴道前壁组织中PⅢNP含量亦明显低于相应对照组(P<0.05)。
     6.相关性分析的结果:绝经前、后组中阴道壁Ⅰ型胶原含量的减少与ICTP表达量的增加显著相关(绝经前组r=-0.876,P<0.01;绝经后组r=-0.842,P<0.01);Ⅲ型胶原与PⅢNP相关性分析的结果:Ⅲ型胶原与PⅢNP呈正相关(绝经前组r=0.732,P<0.01;绝经后组r=0.713,P<0.01)。
     7.不同脱垂程度的POP组Ⅰ、Ⅲ型胶原及代谢标志产物之间的比较结果,绝经前、后组中仅轻型与重型POP患者阴道前壁组织中的Ⅰ、Ⅲ型胶原及ICTP水平比较均有统计学差异(P<0.05),PⅠCP在不同脱垂程度的绝经前、后组中均无显著差异(P>0.05)。
     结论
     1.POP患者阴道前壁组织中Ⅰ型胶原含量均明显减少,提示POP患者阴道前壁组织中Ⅰ型胶原含量减少与POP的发生有关。
     2.绝经前和绝经后POP患者阴道前壁ICTP含量明显增加均与Ⅰ型胶原表达量明显减少呈显著相关,而PⅠCP变化不明显,提示POP患者阴道前壁组织Ⅰ型胶原蛋白减少可能是由于局部Ⅰ型胶原合成代谢无明显变化,主要为降解增多所致。
     3.POP患者阴道前壁组织中Ⅲ型胶原含量均明显减少,提示POP患者阴道前壁组织中Ⅲ型胶原含量减少也参与了POP的发生。
     4.绝经前和绝经后POP患者阴道前壁PⅢNP含量减少均与Ⅲ型胶原表达量明显减少呈显著相关,提示POP患者阴道前壁组织Ⅲ型胶原蛋白减少可能是由于局部Ⅲ型胶原合成代谢明显减少为主。
     5.不同脱垂程度的POP患者阴道前壁组织Ⅰ、Ⅲ型胶原及代谢标志物含量比较,绝经、后组患者阴道前壁组织中的Ⅰ、Ⅲ型胶原及ICTP水平在轻型与重型间有显著差异,但中型-重型、轻型-中型之间均无明显差异,PⅠCP及绝经前PⅢNP各型间无明显差异,可提示POP发展到中至重型时盆底Ⅰ、Ⅲ型胶原代谢改变己呈完全不可逆性,轻型脱垂是POP妇女最佳治疗阶段,POP的治疗尤其是保守治疗要趁早进行。
OBJECTIVE: The aim is to investigate the content of type I &III collagen and their synthesis and degradation products including carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and aminotermimal propeptide of type III procollagen (PIIINP) in anterior wall of vaginal tissue, and to explore whether the metabolic changes in anterior vaginal tissue could contribute to the etiology of pelvic organ prolapse(POP).
     METHODS: Transvaginal biopsies were obtained from anterior vaginal tissue in premenopausal and postmenopausal patients with POP and comparable premenopausal and postmenopausal control groups during transvaginal operations. Sixty-three women participated in the study. They were divided into 4 groups as follows: 16premenopausal patients with POP (group 1), 19 premenopausal patients with neither UI(urinary incontinence) nor POP (group 2), 18 postmenopausal patients with POP(group 3), 10 postmenopausal patients with neither UI nor POP (group 4).The concentration of type I & III collagen, PICP, ICTP and PIIINP in specimen were biochemically detected by enzyme linked immunosorbent assay (ELISA commercial kits), followed by tissue specimen homogenization.
     RESULTS: The content of type I collagen in premenopausal POP group and postmenopausal POP group are significantly lower than that in the control groups(-21.28% and -24.06%, respectively). The content of ICTP reduced significantly both in premenopausal POP group and in postmenopausal POP group. High relativity was found in the variability of type I collagen and ICTP, the correlation coefficient of them was -0.876 (P<0.05) of the premenopausal groups and -0.842 (P<0.05) of the postmenopausal groups. Compared to premenopausal controls and postmenopausal control group, the mean' concentration of PICP was higher in POP groups, premenopausal or postmenopausal, but the difference between them was not statistically significant (P>0.05).
     There was significant difference in the level of type III collagen between the POP groups and control groups whether in premenopausal patients or in postmenopausal patients(-29.70% and -29.18%, respectively, P<0.05). Compared to the control groups, the concentration of PIIINP was also significantly lower in POP patients, whether in premenopausal group or postmenopausal group. Significant positive correlation was found between type III collagen and PIIINP (premenopausal groups: r =0.732 ; postmenopausal groups: r =0.713 ).
     Significant differences of premenopausal groups' content of type I collagen , type III collagen and ICTP were found only between slight stage and gravis stage(P<0.05), while among the postmenopausal groups the content of I collagen , type III collagen , ICTP and PIIINP were found significances between slight stage and between gravis stage(P<0.05). No significant difference was found in varies stages of PICP, whether in premenopausal or in postmenopausal groups(P>0.05).
     As to age, parity and menopausal time, we found that postmenopausal POP patients (group 3) had significantly older age when compared to premenopausal patients with POP(groupl).
     CONCLUSION: The content of type I &IIIcollagen in anterior vaginal tissue are significantly lower in premenopausal and postmenopausal women with POP, while the expression of ICTP significantly elevated and PIIINP significantly reduced. We also found a strong correlation between the quantity of type I collagen and ICTP, and between type III collagen and PIIINP in anterior vaginal tissue, suggesting that collagen metabolism altered in pelvic organ prolapse patients. Increased degradation of type I collagen and less synthesis of type III collagen should result in a decreased concentration of collagen, a less flexible form of extracellular matrix, also suggesting a connective tissue with impaired mechanical function. Those tissues probably were less elastic and less strong, more likely to be broken, which suggested that the degeneration of biomechanical properties in pelvic support construction might lead to the occurrence of POP.
     As to different stage of POP, slight stage and gravis stage had much more significant differences, which suggested that the slight stage maybe the best curable opportunity, especially for the conservative therapy.
     Also, we found that postmenopausal patients with POP (group 3) had significantly older age and much longer postmenopausal time, when compared to premenopausal patients in group 1. Basing on these investigations, we could reached the conclusion that the collagen metabolism in anterior vaginal tissue in postmenopausal patients with POP might be modulated by aging process and reproductive hormones, which suggested that age and the level of estrogen might be involved in the pathogenesis of POP postmenopausally.
引文
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