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The Change of Hepatic Oval Cells and Kinds of Related Cytokines in Biliary Obstruction Model

Author: ZhangChen
Tutor: QinMingFang
School: Tianjin Medical University
Course: Traditional Chinese Medicine
Keywords: bile duct obstruction liver fibrosis Oval cells TGF-β1 TGF-α HGF COLⅠ
CLC: R575
Type: Master's thesis
Year: 2011
Downloads: 7
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Abstract

Background and ObjectiveIn the liver and gallbladder surgery clinical, biliary obstruction and cholestasis are common pathological states. Longer obstruction can cause permanent liver damage. The clinical treatment is ineffective, related to the pathogenesis of basic research has practical significance.The liver progenitor cells.oval cells, has been found in the chronic liver disease such as cirrhosis of the liver, sub-massive hepatic necrosis of liver regeneration, children with congenital extrahepatic biliary atresia, hereditary hemochromatosis, chronic viral hepatitis, hepatocellular carcinoma. This hepatic progenitor cells located in periportal areas, fiber spacing, periportal zone adjacent hepatic parenchyma, and inflammatory pseudo-lobular borders. With the specific markers of the oval cells found, research about oval cells has been hot, especially in the research of liver damage repairing and liver fibrosis. Other studies have proved that multiple organ fibrosis is accompanied by the reactivation of the gene related embryonic development and kinds of cytokines. These provide the latest way in the research of hepatic injury protection, treatment and the formation mechanism of liver fibrosis.In this study, we explore the roles of oval cells and cytokines related to the pathological process in the process of biliary obstruction and hepatic fibrosis, using histological and PCR techniques, by ligating Wistar rats’common bile duct to replicate the pathological states of biliary obstruction.Methods:Male Wistar rat 60. Body weight 250-300g, health and no obvious deformity. They were randomly divided into experimental group and control group. One group (30 only) as the experimental group is carried out nearly portal single-lane ligation (BDL); another group (30 only) as control group is carried out only laparotomy but not ligation. Postoperative raised under the same conditions. The 1,2,3,7,14,21 day after the operation, five in each group were sacrificed. Take right lobe of liver 4% paraformaldehyde fixed histological analysis. Take liver left lobe-80℃frozen for RT - PCR detection reserved.1 Through the naked eye, and HE staining of bile duct obstruction in liver morphological changes at different time points.2 Through immunohistochemistry, observe the number and distribution of oval cells at different time points, by OV-6 marker。3 Through the PCR detection to every purpose:Transforming growth factor (TGFβ1，TGF-α), Hepatocyte growth factor (HGF), Collagen I (COL I), observe each gene expression at different time points.Results1、General results:After Wistar rat biliary obstruction, the liver is yellowing and swelling, oedema and congestion. We can find Formalin fixed part of rat liver with the rough surface samples and getting grey, the performance of early liver fibrosis. The control group: liver specimens, each lobe rosy and smooth surface.2、HE dyeing results:We can see little neutrophil and lymphocytes at the first day; we can a few new born little bile duct without the lumen, a few neutrophil and lymphocytes at the second day;we can see new born of tiny bile ducts and without the lumen small bile duct, neutrophil and lymphocytes more than the second day significantly, liver cell mild degeneration, visible multifocal and flake necrosis, liver tissue collect abbacy visible bile duct proliferation and fibrous tissue cell hyperplasia and an occasional bile duct dilation at the third day; at the seventh day liver cells appear degeneration necrosis incidence increased worse progressively, and degree of hemorrhage and necrosis seen flake, liver tissue bile duct proliferation and fiber hepatis visible; at 14th days lobular structure damage, visible liver cell vacuoles degeneration and necrosis; Postoperative 21 days lobular structural damage more serious, a lot of necrosis of liver cells. Over time and liver damage, fibrosis degree progress gradually deteriorated.3、Immunohistochemical results:OV - 6 immunohistochemical staining cell number and positive distribution with obstruction the extension of time and increase, experimental group and control group have obvious difference. OV - 6 positive cells express parts mainly in collect abbacy bile ducts and liver interstitial new born bile duct and no small bile duct cells lumen of cytoplasm.4、RT - PCR results In the control group and BDL group, we can detect all purpose gene expression in the liver tissue. Statistical analysis showed that the two groups COL I and TGF -β1 have the statistically significant from the first day, HGFand TGF-αhave the statistically significant from the third day. Between BDL groups of different days, COL I and TGF-β1 in 3th-7th days have no statistically significant, HGF in 1th-3th days and 7th-21th days have no statistically significant, TGF-αin 1th-2th days and 7th-21thdays have no statistically significant, while the other statistically significant. The purpose to express a growing trend among the genome, COL I and TGF -β1 grow the fastest at 1th-3th days, TGF -αand HGF grow the fastest at 3th-7th days.Conclusion1、This study find that the liver of the BDL rats present cholestasis, progressive aggravating fibrosis performance. Oval cells Participate in the damage repair process after bile duct obstruction. Its timing change is similar with antifibrosis cytokines, so it may participate in anti fibrosis process.2、Research found that the liver fibrosis in the experimental groups are significantly higher related gene expression than the control groups, with the increase of obstruction of the amount of days express significantly increased. COL I changes represent fibrosis process, TGF-β1 is related to the liver fibrosis process, TGF-αand HGF are related to the antifibrosis process.3、The study found that the period,3th-7th days, is special in the fibrogenic process, 3th day Before the 3th day the main performance is the promoting fibrosis process; from the 3th day anti fibrosis performance begin to appear, promoting fibrosis trend abate, fibrosis become slowly; after the 7th day the liver fibrosis is the continuous progress.

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CLC: > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease
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