The Effects Of Matrine On The Apoptosis And Differentiation Of Rats Hepatic Oval Cells

ObjectivesOval cell proliferation and profiled differentiation were involved in the formation of hepatocellular carcinoma (HCC) precancerous lesions. It was significant to take appropriate measures to block the HCC cell differentiation in cancerprevention and treatment. As the main effective continent of traditional Chinese medicine herb-Sophora flavescens. matrine has been used in the clinical treatment of liver diseases and cancer for several years. In previous studies, this project team discovered that matrine could regulate of Notch and Wnt-1signaling pathway, thus affecting the liver cancer cells oval cells in a variety of biological behaviors, including:inhibition of proliferation and promote apoptosis and differentiation. The above researches suggested that matrine had potential role in prevention of HCC. However, further comprehensive and specific cytological and molecular biological mechanisms are still to be studied. In this study, matrine was applied as prevention intervention in SD rat hepatic oval cell proliferation model and in vitro of matrine Wb-f344rat hepatic oval cells.Observation on oval cell proliferation, differentiation, apoptosis and autophagy role in order to explain the mechanism of matrine for the prevention and treatment of HCC precancerous lesions (oval cell hyperplasia).MethodsAccording to randomized principle, a total of50SD rats were divided into the3groups. Animal oval cell proliferation model was established under the control of " matrine intervention+DEN+Solt-Farber". Organizations in the oval cell structure were observed by light and electron microscope. Using immunohistochemistry assay and TUNEL assay, to test the expression changes of AFP, CK-19, LC3rat liver oval cells and apoptosis of oval cells sepatately. Furthermore, in vitro of matrine Wb-f344rat hepatic oval cells model was established and the expression changes in ALBmRNA were observed by Real time PCR.Statistical methods:SPSS17.0statistical software was applied for statistical analysis. Metering informations were expressed as mean±standard deviation (X±s), and normal data using analysis of variance test, meanwhile the non-normaldata using non-parametric Wilcoxon rank sum test. P<0.05indicates that the difference was significant.ResultsBased on established criteria, DEN+Solt-Farber rats model was successfully constructed with successful rate of87.5%; immunohistochemical detection showed that matrine intervention could significantly reduce the proliferation of oval cells and the inflammatory cell invasion. AFP and CK-19expression of oval cells were decreased (p<0.05), meanwhile the expression changes in LC3were not significant (p>0.05). Compared with the normal group, TUNEL assay model group and matrine intervention group increased expression of apoptotic foci of periportal oval cells. Compared with the control GAPDH, WB-F344cell marker gene molecules ALB mRNA, induced by matrine, expression increased significantly (p <0.05).ConclusionIt was found in this study that matrine could promote apoptosis of hepatic oval cells, and could inhibit the differentiate into mature liver cells. Matrine had little effect to autophagy oval cells in vivo. By promoting oval cell apoptosis. differentiation, inhibition of proliferation play a role, matrine might be the role of prevention and treatment of HCC precancerous lesions, thereby, increasing feasiblesex of HCC early prevention.