Expressions Of Matrix Metalloproteinase-13,14 And Tissue Inhibitor Of Metalloproteinase-1 In The Vaginal Wall Tissue Of The Women With Stress Urinary Incontinence

Female pelvic floor dysfunction(PFD) mainly includes stress urinary incontinence(SUI) and pelvic organ prolapse(POP). Stress urinary incontinence (SUI) is defined as when the intravesical pressure exceeds the maximum urethral pressure, people show leakage of urine,At the same time,it occurs in the absence of detrusor contraction,It is a common gynecological disease which seriously affects the living quality of the patients.SUI is a kind of involuntary urine outflowing caused by a sudden increase in abdominal pressure not from the tension of the detrusor muscle contraction. Stress urinary incontinence have a higher prevalence and incidence with age,As the age increases,the incidence rate increased,Foreign large sample epidemiological survey showed 12.5% of women suffer from SUI, the prevalence rate of 45～65-year-old woman is 10%～27%. SUI and POP is often accompanied by occurrence, studies have found that 80% of patients with SUI associated with POP, and about 69% of patients with SUI associated with SUI,so,the researchers proposed that they may even have a common pathogenesis.The pathogenesis of stress urinary incontinence is not very definitude at the present time. The occurrence of SUI are closely related to the integrity of the pelvic floor structure and function. Pelvic support organization is composed mainly by the ligaments and fascia,well,The connective tissuen is composed mainly of collagen, The reduction in collagen quantity of SUI is thought to be a common factor contributing to the development of SUI and POP,as they often seen concurrently. The main reason of reduction in collagen quantity is increased collagen degradation.Matrix metalloproteinases (MMPs) is the main proteolytic enzymes to degrade the collagen.So far,six major categories with more than 20 family members of MMPs have been found,and their performances have been clarified.A variety of enzymes all have a certain degree of substrate specificity.MMP-13, also is known as collagenase-3 and its substrate is very broad.It can hydrolyzeⅠ-type,Ⅱ-type,Ⅲ-type, IV-type collagen,gelatin,and basement membrane components (including the polysaccharides protein, mucin).MMP-14 belongs to membrane-type matrix metalloproteinase,it has a variety of biological functions,it can effect a variety of extracellular matrix components,cell adhesion molecules and other MMPs and involved in many important physiological and pathological processes directly or indirectly.MMP-14 mediate proMMP-13 activation in vitro and in cell model systems.Tissue inhibitor of metalloproteinases (TIMPs) is a specific inhibitor of MMPs, which bind specifically to MMPs and inhibit their activity,They can inhibit the activity of MMPs and the activation of zymogen, resulting in the reducing of MMPs activity and the depressing of collagen degradation. It is the most important enzymes of the collagen metabolism regulation. Its changes may be an important factor for the changing of the pelvic floor collagen metabolism in the patients with SUI.4 family members of TIMPs have been found,TIMP-1 is widely present in the organization and body fluids,which bind to most of MMPs and inhibit their activity.MMP-13 play a major inhibition of TIMP-1 In vivo.Chen found that the expression of TIMP-1mRNA decreased in the vaginal wall tissues of female patients with SUI.ObjectiveIn this thesis,take tissue from the vaginal wall,use immunohistochemistry and image analysis method to detect the expression level of the MMP-13,MMP-14 and TIMP-1 in the SUI patients,and consequently analyze the relationship of various indicators to further understand the pathophysiology change of the SUI,and,as a conclusion,to provide a theoretical guideline for the prevention and also the treatment of SUI.Materials and Methods1 MaterialsChoose 30 cases with SUI group and 30 cases with POP group from the gynecological hospital patients in the Third Affiliated Hospital of Zhengzhou University from july 2008 to January 2009,and select the same period non-functional ovarian tumor and cervical intraepithelial neoplasia 30 cases of patients observed as a control group.Every group meets the diagnostic criteria. Patients were not taken off estrogen drugs Within 6 months,moreover,pelvic floor nerve function and routine urine analysis was normal.The 3 Group patients there was no significant difference in age,parity,body mass index(P>0.05).Patients sufferd from SUI underwent the surgery of TVT-O, patients sufferd from POP underwent the surgery of Pelvic sling or Anterior vaginal repair.control group underwent the surgery of vaginal hysterectomy or abdomino hysterectomy.2 MethodDetecting the expression of MMP-13,MMP-14 and TIMP-1 in the three groups by immunohistochemistry.3 Image and results analysisObservatd each slice comprehensively, selected five high-powered field of vision with a representative of significancerandomly.The positive expression of MMP-13 and TIMP-1 locate in the cytoplasm.The positive expression of MMP-14 locate in the cytoplasm or nucleus.Using Image-Pro Plus 6.1 immunohistochemical analysis software computes corrections for the cumulative optical density (IOD) of each field of vision in the immunohistochemical.4 Statistic analysisSPSS15.0 was performed to analysis the study data.All the data was express as x±s.Means of every group were compared by One-Way ANOVA.Correlations between groups were analysis by Pearson.Statistical significance was defined asα= 0.05.Results1 The expression of MMP-13 in the anterior vaginal tissueMMP-13 is observed in the anterior vaginal tissue of the three groups of patients.The expression in SUI group and POP group were stronger than the control group(P<0.05),But there is no significant difference between the SUI group and the POP group(P> 0.05). 2 The expression of MMP-14 in the anterior vaginal tissueMMP-14 is observed in the anterior vaginal tissue of the three groups of patients.The expression in SUI group and POP group were stronger than the control group (P<0.05),But there is no significant difference between the SUI group and the POP group(P>0.05).3 The expression of TIMP-1 in the anterior vaginal tissueTIMP-1 is observed in the anterior vaginal tissue of the three groups of patients. The expression in SUI group and POP group were lower than the control group (P<0.05),But there is no significant difference between the SUI group and the POP group (P>0.05).4 Statistic analysis on MMP-13,MMP-14 and TIMP-1There are negative relationship between the expressions of TIMP-1 and the those of MMP-13 and MMP-14 in the vaginal wall tissue of the women with SUI(r=-0.844,P<0.05;r=-0.782,P<0.05),then,There are positive relationship between the expressions of MMP-13 and MMP-14 in the vaginal wall tissue of the women with SUI(r=0.914, P<0.05).Conclusion1 TIMP-1 participates in the occurrence of SUI through inhibiting and eventually reducing the activity of MMP-13 and MMP-14.2 MMP-14 mediate proMMP-13 activation in pelvic floor connective tissue, it can effect a variety of extracellular matrix components directly or indirectly,moreover, Increased of MMP-13 and MMP-14 may cause the degradation of collagen in total may play an important role in the development of SUI.