The Expression Of Fibulin-3, Tissue Inhibitor Of Metalloproteinase-3 And Elastin In The Vaginal Wall Tissue Of The Women With Stress Urinary Incontinence

Stress urinary incontinence (SUI) is defined as a kind of involuntary urine outflowing,which happens when the abdominal pressure abruptly increases,but not from detrusor muscle contraction or the tension of the bladder.It often occurs simultaneously with genital organ prolapse.SUI severely affects the daily life of the patinets,causing the living quality of the patinets decreased,at the same time it brings about a grave burden on socienty and economy.The pathophysiology of female SUI is complex.A great quantity of researches on the pathogenesis of SUI has been carried on,including anatomy,morphology and fuction,but the certain mechanism is not well understood.Mutiples of researches have shown that the changes on the structures and functions of the pelvic floor connection tissues may play a key role on the development of SUI.Fibulin-3(also known as EFEMP1) is an extracellar glycoprotein broadly expressed throughout the body during development and in adult tissues.It is one of 8 members of the fibulin family of proteins.Fibulin-3 interacts with another basement membrane protein,extracellar matrix protein 1(ECM1).It also interacts with tissue inhibitor of metalloproteinase-3(TIMP-3),collagen XVIII and elastin monomer- tropoelastin.These interactions likely contribute to the integrity of basement membrane zones and the stabilization of extracellar matrix(ECM).Tissue inhibitor of metalloproteinases (TIMPs) is a family of secreted proteins that encoded by multiple genes, which is the natural and specific inhibitor of matrix metalloproteinases(MMPs).TIMPs can bind specifically to MMPs,playing an important effect on maintaining the structure of ECM.The plevic floor connective tissue is composed of liganment and fascia,whose mechanical and supportive properties are determined by the structure of the main molecules that constitute the tissue (collagen, elastin, proteo-glycans and glycoproteins),their overall proportions and their interactions with each other.Collagen and elastin,as the main components of the connective tissue,play an important role on the function of pelvic floor supporting tissue.The previous studies on the pelvic floor dysfunction(PFD) connective tissue primarily focus on the changes of collogen. Investigators have documented changes on the genes concerned with elastin metabolism in the vaginal wall in PFD patients,suggesting a potential role for elastin remolding in the etiology of SUI.ObjectiveThe aim of this study is to detect the expression levels of Fibulin-3,TIMP-3 and elastin in vaginal tissues of SUI patients,by immonuhistochemistry, and at the same time analyze the correlation of various index to further explore the role of the changes in the pelvic supporting tissue structure and metabolism on the development of SUI.Materials and Methods1. SubjectsNinety women participated in the present study,all of them were recruited in the Third Affiliated Hospital of Zhengzhou University from August 2009 to February 2010.The patients were divided into three groups:30 patients with SUI,30 patients with POP and 30 patients with benign gynecological disease as controls.All subjects in this study met the diagnostic criteria,and had no previous pelvic floor operation history.The patients recruited were treated as follow:women with SUI,underwent a trans-obturator vaginal tape(TVT-O),TVT-S or vaginal anterior wall repair;women with POP,underwent the surgery of anterior pelvic sling or vaginal anterior wall repair;women in the control group underwent a vaginal or abdominal hysterectomy. Approximately 0.5cm X 0.5cm X 0.5cm of full-thinkness, vaginal anterior wall was exicised all participants.2.methodMeasuring the expression of Fibulin-3,TIMP-3 and elastin in all the participants by immunohistochemistry.3. AssessmentUsing the Biosens Digital Image Analysis System to examine the average gray value of positive expression area of Fibulin-3,TIMP-3 and elastin.4.Statistical analysisSPSS 16.0 was used to analysis the data.All values were expressed as mean±standard error of mean(S.E.M) and differences betweeen the three groups were compared by One-Way ANOVA,while LSD was employed to analyse the differences betweeen every two groups.Correlation between different group was analysed by Pearson.Statistical significance was defined as a=0.05.Results1. The result of stainingAll exit in the vaginal tissue,with some sections intense and some others weak.The positive expression of Fibulin-3 and elastin primarily diffused distribute in the extracellar matrix,while the positive expression of TIMP-3 locates in the cytoplasm.2. The expression of Fibulin-3①The expression level of Fibulin-3 in SUI group is lower than that in the control(P<0.05),②The expression level of Fibulin-3 in POP group is lower than that in the control(P<0.05),③There is no significant difference between the SUI group and the POP group(P>0.05). 3. The expression of TIMP-3①The expression level of TIMP-3 in SUI group is lower than that in the control(P<0.05),②The expression level of TIMP-3 in POP group is lower than that in the control(P<0.05),③There is no significant difference between the SUI group and the POP group(P>0.05).4. The expression of elastin①The expression level of elastin in SUI group is lower than that in the control(P <0.05),②The expression level of elastin in POP group is lower than that in the control(P<0.05),③There is no significant difference between the SUI group and the POP group(P>0.05).5. Correlation analysis resultsThere is positive correlation between Fibulin-3 and TIMP-3(r为0.734, P<0.05) in SUI group,and so it is TIMP-3 and elastin(r为0.718, P<0.05).ConclusionThe decrease of Fibulin-3,TIMP-3 and elastin may contribute to the development of SUI in common.