An Experimental Study On Functional Differentiation Of Liver Cells In Hepatic Bile Duct Or Portal Vein Deprived Lobe

Objective: The aim of this study is to establish a rat self-control model with the bile duct deprived (BDD) and the portal vein deprived (PVD) hepatic lobe and to investigate the reservation value of BDD lobe by an observation of the phenomenon and rules of morphological changes and functional differentiation of hepatic cells in the two lobes. Methods: We removed the left and caudate lobes of rat and just reserved its quadrate and right lobes. Two weeks later, the right hepatic bile ducts were embolized with Cyanoacrylate and then ligated to prepare the BDD lobe. The portal vein of quadrate hepatic lobes was ligated as the PVD lobes. We set four groups as follows: Group S with sham operation as an undisposed blank control, Group BL with the right lobe bile duct embolized and ligated, Group PL with the quadrate lobe portal vein ligated and Group BPL with the right lobe bile duct embolized and ligated and meanwhile the quadrate lobe portal vein ligated. The observation period is from 2 weeks to 2 months after the bile duct or portal vein ligated. The bile duct and portal vein casting specimens of these four groups were prepared by a perfusion with barium and gelatin solution. Three-dimensional micro-computerized tomography (Micro-CT) data sets were acquired to observe the morphological changes of bile duct and portal vein of the livers and whether there were communicated branches between the right and quadrate lobes in order to estimate the feasibility of the model. The morphological and functional changes of the hepatic lobes were investigated through the test and examination as measurement of split hepatic vein, hepatic histopathological screening by HE and PAS dyeing paraffin slice, ultra structural study by transmission electron microscope (TEM) and liver tissue proteomics research.Results: (1) The rat's survival rate after operation was 100%. No jaundice was observed. The gross morphology and the ratio of two lobes showed that the BDD lobe had no obvious atrophy and fibrosis while the PVD lobe had. (2)Micro-CT images exhibited directly the morphological changes of the hepatic bile duct and portal vein and no communicated branches or side circulation situation were observed between the two lobes. (3)The serum liver function assay of split hepatic vein blood showed that ALT and AKP increased in different degree, the plasma albumin and fibrogen decreased while the blood bilirubin and total bile acid level were not significantly increased. Compared to the undisposed blank Group S, several indexes had significant differences. Compared to the self-contrast untreated lobe, the index of PVD lobe changed obviously and the BDD lobes changed little. (4) Histopathology study revealed that the structure of hepatic lobule of the BDD lobe had no distinct changes. That of the PVD lobe ruined significantly and became worse by the time after operation. The number of hyperplasia bile canaliculus increased. (5) Ultra structure study showed that the BDD liver cells have plenty of mitochondrions, rough endoplasmic reticula (RER) and free ribosomes. Its bile capillary cavity was narrow and the microvillus destroyed obviously. The PVD liver cells revealed a decreased RER, plenty of smooth endoplasmic reticula. Its bile capillary structure showed relatively normal. (6)Proteomics study revealed that the expression of albumin, apolipoprotein A-I and triosephosphate isomerase in the BDD lobe had no obvious reduction and Z and Y protein decreased significantly. The PVD lobe showed a reversed change.Conclusion: Under the condition of BDD and PVD, liver cells show functional differentiation to some extent. The BDD lobe remains most liver functions such as protein synthesis and nutrition metabolism and shows no atrophy during the observation period. It suggests that the BDD lobe have reservation value. This study provides a preliminary experimental basis of preserving the liver lobe with the bile duct removed or ligated in some emergency and specific clinical situation. To clarify the exact mechanism of liver cells functional differentiation, a thorough research in the level of gene and protein expression is needed.