The Expression Of XIAP In Middle Ear Cholesteatoma And The Relationship With Caspase-3

Objective:The cholesteatoma of middle ear is a frequent clinical disease, which is similar to tumer of its persistent energy for growth and aneretic potentia to sclerotin .A good many internal and overseas experts have paid close attention to the reaserch of middle ear cholesteatoma generally. The cholesteatoma endepidermis has powerful proliferative energy and higher apoptosis .The apoptosis of cholesteatoma endepidermis is closely correlated with the accumulation of keratose in middle ear,and the characteristic of apoptosis is significant to the research of nosogenesis and the therapy of cholesteatoma.The Caspase family as a key molecule group can regulate the apoptosis. Caspase-3 has the closest relation with apoptosis ,and it particapate in the apoptosis which is induced by many factors.XIAP(X-linked inhibitor of apoptosis) is the most effective in IAP(inhibitor of apoptosis) family.It can inhibit the Caspase directly and block the formation and development of apoptosis.The purpose of this study is to examine the expression of XIAP,Caspase-3 and the apoptosis states in middle ear cholesteatoma,trying to discuss the relationship of XIAP,Caspase-3 and apoptosis state in middle ear cholesteatoma, investigate the possible role of XIAP,Caspase-3 in middle ear cholesteatoma and further explore the pathogenesis of middle ear cholesteatoma .Methods:Specimens of 25 cholesteatoma and 10 normal externalear auditory canal skin were collected from the mastoidotympanectomy in the Second Clinical Hospital of Shanxi Medical University between June 2005 and July 2007, and were studied by pathology .All of the specimens were performed by immunohistochemical method using polyclonal antibodies of XIAP and Caspase-3. The apoptosis states of the 2 tissues were determined by TUNEL method.Results:1.There was no or less expression of XIAP in cholesteatoma endepidermis ,while the XIAP mainly concentrate in basal layer cell-substance of normal externalear auditory canal endepidermis.Comparing with normal externalear auditory canal skin,the expression of XIAP protein obviously decreased in cholesteatoma(Z=-2.411, P<0.01). 2. Caspase-3 mainly concentrate in prickle cell layer and granular cell layer of cholesteatoma endepidermis, while it located sparsely in granular cell layer of normal externalear auditory canal endepidermis. The expression of Caspase-3 protein significantly increased in cholesteatoma endepidermi(sZ=-2.877, P<0.01).3. Most of died cells expressed densely in prickle cell layer and granular cell layer of cholesteatoma endepidermis,while there were sparse died cells in full-thickness of normal externalear auditory canal endepidermis. The apoptosis were significantly lower than that in cholesteatoma tissue ( Z=-2.712, P<0.01 ) .4.The correlation analysis in cholesteatoma endepidermis was shown: the expression of XIAP was inversely correlated with Caspase-3 and apoptosis(rp=-0.569 , -0.527, P<0.01),respectively; There was a direct correlation between Caspase-3 and apoptosis (rp=0.540,P<0.01).Conclusions:1. In cholesteatoma endepidermis ,the died cells were located widely in full-thickness . Comparing with normal externalear auditory canal skin, the quantity of died cells was obviously decreased in cholesteatoma .It proved that there was strong apoptosis in cholesteatoma endepidermis. 2. In cholesteatoma endepidermis ,there was no or less expression of XIAP and high expression of Caspase-3 which mainly concentrate in prickle cell layer and granular cell layer .The expressions of the 2 protein were closely related with apoptosis.It suggested that they participate the regulation of apoptosis and have important roles in the formation and development of cholesteatoma .3.In cholesteatoma,the expressions of XIAP decreased while that of Caspase-3 increased and there was a inverse correlation between eath other. We infered that the inhibition of Caspase-3 is relieved by the decrease of XIAP ,and the activity of Caspase-3 is reinforced in cholesteatoma,that accelerate the apoptosis of cholesteatoma endepidermis and accumulation of keratose .The abnomal expressions of the 2 protein may be a improtent factor of nosogenesis in cholesteatoma .