| Objective:Pelvic organ prolapse (POP) is a prevalent condition that negatively impacts the quality of life of the middle-aged women and the etiology has not been clearly defined. Pelvic organ prolapse is associated with defects in the structural and functional integrity of connective tissue of the pelvic floor including elastic fibers and collagen fibers. The composition changes and metabolic abnormalities may be one of the pathogenesis of POP. Recent study suggests that reduction of functional elastic fibers and disordered elastic fiber homeostasis could underlie the etiology of POP. Fibulin-5 is the newest member of the fibulin family that is the extracellular matrix protein. It is playing a crucial role in the formation of elastic fibers. And lysyl oxidase-like 1 (LOXL1) is the key enzyme during the development, maturation and maintaining a stable internal environment of the elastic fiber. This study examined the expression of Fibulin-5 and LOXL1 and the pathologic changes to elastic fibers in uterosacral ligaments, vaginal anterior and posterior wall tissue, which designed to explore the correlation between the changes of the structure and function of pelvic floor tissue and occurrence of POP and new ideas in the prevention and treatment of POP.Methods:All the patients were chosen from the department of gynecology and obstetrics of the second hospital of Hebei Medical University during January 2009 to October 2009.15 women with POP asking for surgery were recruited as study group and 10 women with benign gynecological diseases asking for surgery as control group. Enrolled women were no history of using hormones within the past three months, and there were no significant differences between two groups of their age, parity and body mass index (BMI) (P>0.05). After obtaining the agreement of hospital Ethics Committee and informed consent, uterosacral ligaments and (or) vaginal anterior and posterior wall were sampled in a standardized fashion from women during operation. The specimens from the tissues were saved in manner of liquid nitrogen and formalin-fixed respectively.1 Real-time Quantitative Polymerase chain Reaction (Real-time RT-PCR) was performed to measure mRNA level of Fibulin-5 and LOXL1. The level was represent by Relative Quantitative value(RQ value). Using SPSS 13.0 statistical software, the results were analyzed using t test and Pearson correlation analysis, and data were represent by mean±SD(x±s) (P<0.05).2 The expression of Fibulin-5 and LOXL1 was detected by immunohistochemistry, and basing on the area and the intensity of cell staining, expressive intensity was evaluated. The results were analyzed using Fisher's Exact Test and Spearman's correlation analysis (P<0.05).Results:1 General informationThere were no significant differences between two groups in their age, parity and BMI.2 The expression of mRNA level of Fibulin-5 and LOXL12.1 The expression of mRNA level of Fibulin-5 in uterosacral ligaments, vaginal anterior and posterior wallComparing with control group (n=10), significant decrease in the expression of mRNA of Fibulin-5 was found in uterosacral ligaments of patients with POP (n=15) (1.530±0.340 vs 0.695±0.215, P＜0.05). The average level of Fibulin-5 expression in POP-Q stage I, II, III (five cases of each stage) was 0.935,0.633,0.472, respectively. Significant difference was noted among them and the level of expression was decreased with increasing degree of prolapse (P<0.05). Comparing with control group (n=10), there was also significant decrease in the expression of mRNA of Fibulin-5 in vaginal anterior wall of patients with POP (n=10) (1.731±0.091 vs 0.979±0.030, P＜0.05). 2.2 The expression of mRNA level of LOXL1 in uterosacral ligaments, vaginal anterior and posterior wallComparing with control group (n=10), significant increase in the expression of mRNA of LOXL1 was found in uterosacral ligaments of patients with POP (n=15) (0.434±0.288 vs 1.920±0.570, P<0.05). The average level of LOXL1 expression in POP-Q stage I, II, III (five cases of each stage) was 1.389,1.870,2.647, respectively. Significant difference was noted among them and the level of expression was increased with increasing degree of prolapse (P<0.05). Comparing with control group (n=10), there was also significant increase in the expression of mRNA of LOXL1 in vaginal anterior wall of patients with POP (n=10) (0.624±0.017 vs 0.969±0.044, P＜0.05).2.3 Correlation'There was negative correlation between the expression of mRNA level of Fibulin-5 and LOXL1 (r=-0.717, P＜0.05).3 The expression of Fibulin-5 and LOXL13.1 The expression of Fibulin-5 in uterosacral ligaments, vaginal anterior and posterior wallFibulin-5 was expressed mostly in extracellular matrix in uterosacral ligaments, vaginal anterior and posterior wall. Comparing with control group, the positive rate of Fibulin-5 expression in uterosacral ligaments was decreased in patients with POP (80%(8/10) vs 26.7%(4/15), P＜0.05); And there was also significant decrease in the positive rate of Fibulin-5 expression in vaginal anterior wall and posterior wall of patients with POP (80%(8/10) vs 30%(3/10), P＜0.05).3.2 The expression of LOXL1 in uterosacral ligaments, vaginal anterior and posterior wallLOXL1 was expressed mostly in cytoplasm of fibroblasts and smooth muscle cell. Comparing with control group, the positive rate of LOXL1 expression in uterosacral ligaments was increased in patients with POP (40%(4/10) vs 86.7%(13/15), P＜0.05); And there was also significant increase in the positive rate of LOXL1 expression in vaginal anterior wall and posterior wall of patients with POP (20%(2/10) vs 70%(7/10), P<0.05; 10%(1/10) vs 60%(6/10),P<0.05).3.3 CorrelationThere was positive correlation between the expression of Fibulin-5 and LOXL1 (r=-0.653, P＜0.05)Conclusions:1 The research examined the expression of mRNA level and protein level of Fibulin-5 and LOXL1. Its test results showed that there was decreased expression of Fibulin-5 and increased expression of LOXL1 in uterosacral ligaments, vaginal anterior and posterior wall tissues in patients with pelvic organ prolapse, which was associated with the degree of prolapse. We could know that the changes of Fibulin-5 and LOXL1 expression brought the possibility of defects in elastic fibers synthesis and promoted the incidence of POP.2 There was negative correlation between Fibulin-5 and LOXL1.We suppose that there would be some relatives between them by some way.
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