| Background:Splenomegaly is one of the complications of portal hypertension and chronic liver diseases that potentially influence the morbidity and lower patients'quality of life. The incidence of splenomegaly in cirrhosis varies from 36% to 92% in different series. Especially in China, decompensated cirrhosis induced by virus hepatitis is an important cause of splenomegaly. Splenomegaly may lead to the oppression of abdominal organs and therefore result in corresponding symptoms. Very enlarged spleens may be at risk for spontaneous rupture or rupture after minor trauma. Up to date, there is no specific medical therapy for splenomegaly. YKL-40 belongs to'mammalian chitinase-like proteins'. Until now the physiological function of YKL-40 is unknown in detail. It has been reported that this glycoprotein maybe contribute to tissue remodeling and degradation of extracellular matrix. An intense expression of YKL-40 protein in alveolar macrophages of idiopathic pulmonary fibrosis patients and of asthma patients demonstrates that it is evolved in tissue remodeling and fibrosis. YKL-40 also induces the proliferation of chondrocytes and synovial cells. Collectively, these data suggest that YKL-40 is involved in the pathologic process of human diseases with tissue remodeling. However, whether YKL-40 contributes to tissue remodeling of spleen associated to portal hypertension was still unknown. So in this study immunohistochemistry, western blot and Masson trichrome staining were used to detect expression of YKL-40 and MMP-9 and degree of fibrosis in spleen of portal hypertension combined with clinical features in order to explore the function of YKL-40 in fibrosis process of splenomegaly and possible cell signaling way.Objective:The expression of YKL-40 was studied in spleen of portal hypertension, and the function of YKL-40 in process of fibrosis in spleen associated to portal hypertension and correlation with other clinical features were analyzed. According to the study of relationship with the expression of MMP-9, some possible ways that YKL-40 make function in fibrosis process was found. All the results were hoped to give some new theory support to help diagnosis and treatment of splenomegaly in portal hypertension.Methods:1. Immunohistochemical method was used to detect the expression of YKL-40 and MMP-9 protein in spleen of portal hypertension. The correlation between expression of YKL-40 with MMP-9 protein and other clinical features were analyzed.2. Western blotting method was used to semiquantitatively detect the expression of YKL-40 and MMP-9 protein in spleen of portal hypertension and correlation between expression of YKL-40 with MMP-9 protein and other clinical features were analyzed combined with results of immunohistochemical method.3. Masson trichrome staining method was used to detect the fibrosis degrees of spleens associated to portal hypertension. The correlation between expression of YKL-40 and the fibrosis degrees of spleens was analyzed.Results:1. Positive expression of YKL-40 was a cytoplasmic pattern. In biopsies from patients with portal hypertension staining for YKL-40 antigen was found in areas with splenic marginal zone, red pulp but seldom detected in splenic corpuscle. Positive-stained were also detected in some vascular smooth muscle cells. Expression of YKL-40 in enlarged spleens of portal hypertension was significantly higher than that in normal spleen (P<0.05), and its expression was significantly associated with Child-Pugh Classification (P<0.05).Furthermore, the statistical correlation between overexpression of YKL-40 and Free Portal Pressure (FPP) was found(R=0.499, P<0.01). Positive expression of YKL-40 was a cytoplasmic pattern, mainly located in macrophages or neutrophils, And interestingly, expression of MMP-9 in normal spleen was indeed higher than that in enlarged spleen (37.39±0.75 % versus 25.11±0.83 % ;P<0.01) ,and significant correlation was found between YKL-40 and MMP-9(correlation coefficient is -0.839, P<0.01 ).2. In western blotting method detection, expression of YKL-40 in enlarged spleens of portal hypertension was significantly higher than that in normal spleen (P<0.05), and its expression was significantly associated with Child-Pugh Classification (P<0.05). Expression of MMP-9 in normal spleen was significantly higher than that in enlarged spleen (P<0.05).3. Histomorphological analysis was carried out to detect the presence of fibrosis in the spleen by Masson trichrome staining, and a considerable amount of fibrosis extending to the entire splenic parenchyma was found in portal hypertension patients, compared with normal people(P<0.01 ). Additionally, the Spearman'sρtest showed that expression of YKL-40 was correlated with fibrosis area of spleen (correlation coefficient is 0.857, P<0.01)Conclusion:Expression of YKL-40 in enlarged spleens of portal hypertension was significantly higher than that in normal spleen, and statistical correlation between YKL-40 with FPP and Child-Pugh Classification were found. Furthermore, the Spearman'sρtest showed that expression of YKL-40 was correlated with fibrosis area of spleen. All above mentioned highly indicated YKL-40 may make function in fibrosis process of splenomegaly of portal hypertension. Negative correlation was found between expression of YKL-40 and MMP-9, which indicated YKL-40 may promote fibrosis in spleen by inhibiting expression of MMP-9 in process of portal hypertension. In conclusion, YKL-40 maybe a key molecular mechanism involved in fibrosis development of splenomegaly associated to portal hypertension... |
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