Effects Of MMP-7 And MMP-9 On The Pathogenesis Of Hemorrhoids

Objective:To investigate the pathological variations in internal hemorrhoids tissue,and detect the expression of matrix metalloproteinase-2(MMP-2), MMP-7 and MMP-9, thereby to analyze their relationship and to determine the role of MMPs in the pathogenesis of hemorrhoids.Methods:1) During May 2007 to October 2007, 26 patients with third-fourth degree hemorrhoids were enrolled in department of general surgery of the first affiliated hospital surgery of Shantou University Medical College. Internal hemorrhoids tissue samples were obtained form these patients after Procedure for Prolapse and Hemorrhoids ( PPH ). At the same time, normal anal cushion samples were obtained form 16 patients with rectal cancer after Miles'procedure.2) Routine Hematoxylin-Eosin, aldehyde-fuchsin staining for elastic fibers and Van-Gieson staining for collagen fibers were used to investigate the pathological variations in normal anal cushion and internal hemorrhoids tissues.3) The expression of MMP-2, MMP-7 and MMP-9 in normal anal cushion and internal hemorrhoids tissues were detected by immunohistochemical staining. 4) All of statistical analysis was performed with statistical package SPSS version 13.0 software.Results:1) Compared with the corresponding normal anal cushions, the mucous membrane of hemorrhoidal tissues is thinner, and there was obvious mucosal injury in the mucous of hemorrhoidal tissues. The subepithelial vessels of the hemorrhoidal tissues showed obvious structural impair and retrograde changes, include hyalinization, decrease of smooth muscle, increase of collagen fibers, rupture of the fibroelastic tissues. In addition, thrombosis and subsequent ischemic changes were observed. In connective tissue of the hemorrhoidal tissues, the collagen fibers showed increase, the smooth muscle and the elastic fibers showed hypertrophy, distortion, rupture and tortility. There were much erythrocyte and mononuclear macrophage in the hemorrhoidal tissues, also.2) MMP-2 protein expressing localized to glandular tissue and interstitial tissue, and there was no obvious difference between normal anal cushion and internal hemorrhoids tissues ( P﹥0.05 ).3) MMP-7 protein expressing mainly localized to glandular tissue, and there were statistically significantly difference between normal anal cushion and internal hemorrhoids tissues ( P﹤0.05 ).4) MMP-9 protein expressing localized to glandular tissue and interstitial tissue, and there were statistically significantly difference between normal anal cushion and internal hemorrhoids tissues ( P﹤0.05 ).5) According to the statistical method of Spearman's rank correlation, there are positive correlations of the expression levels between MMP-7 and MMP-9 ( P﹤0.01 ).Conclusions:1) The anal cushion of hemorrhoids disease patients was show significant pathological changes. The pathological changes include decrease in elastic fibers, increase in collagen fibers, the hypertrophy, distortion, rupture, tortility and retrograde changes of smooth muscle and fibroelastic tissues, structural impair of cavernous vessels and thrombosis. These pathological changes of supporting structure in anal cushion are the basis of pathogenesis and development of hemorrhoids.2) As the important members of MMP family, MMP-7 and MMP-9 can disintegrate the components of the extracellular matrix ( ECM ), include collagen ( major in IV-Collagen ), gelatin, elastic fibers, elastin, laminin, and so on. The expression levels of MMP-7 and MMP-9 in internal hemorrhoids tissue were significantly higher than in normal anal cushion, and there are positive correlations of the expression levels between MMP-7 and MMP-9. It is showed that the degeneration effect of MMP-7 and MMP-9 on supporting structure in anal cushion is one important mechanism of pathogenesis and development of hemorrhoids, and MMP-7 and MMP-9 may be have a synergism effect on the process.