The Effects Of Bile Acid On Hepatocytes Apoptosis And Liver Regeneration With Obstructive Jaundice Rats Following Partial Hepatectomy With Different Biliary Drainages

Background and Objective:The Hilar Cholangiocarcinoma is one of the problems of liver and gallbladdersurgery, the prevalence of it has a tendency to rise year by year. Most of patientsare complicated with different levels of obstructive jaundice (OJ). The OJpatients may die of liver failure after partial hepatectomy (PH) due to thecomplications, such as infection, septicemia, malnutrition. Previous researchshows that preoperative biliary drainage is very necessary for OJ patients. Ourprevious research confirms that the internal drainage(ID) is superior to externaldrainage(ED) in liver regeneration after PH, but the mechanism are unclear. Themajor difference of ID and ED is whether the biles flow into the intestine,therefore, one of the major reasons of the differences in liver regeneration afterPH following ID and ED is bile acids (BA) metabolism properly.The Bile acid is a generic terms for Ursodeoxycholic acid in the bile, It canadjust the metabolism of bile acid、energy metabolism and inhibiting intestinethe bacteria over-proliferation in intestine. Whether the bile acid by influencing the liver cell apoptosis thus Impact of liver regeneration？In this experiment, through comparing the Exogenous bile acid intervention ofobstructive jaundice rats following partial hepatectomy with different biliarydrainages，Liver function、Liver regeneration rate, mitotic index, the bloodconcentration of total bilirubin, serum bile acid level, Liver cell apoptosis indexand Bax and Bcl-2expression differences, Further discussion the Exogenousbile acid intervention of obstructive jaundice rats following partial hepatectomywith different biliary drainages Mechanism of liver cell apoptosis andregeneration of differences.Materials and Methods:Using50Male adult Sprague-Dawley rats were randomly assigned to Fivegroups: obstructive jaundice group (OJ: n=10)、internal biliary drainage group(ID: n=10)、external drainage group (ED: n=10)、external drainage+0.2%CAgroup (ED+CA: n=10) and sham operation group (SH: n=10). The SD ratsmodel of obstructive jaundice was established by common bile duct ligation anddivision. After7days, internal and external biliary drainage were built indifferent groups by another operation. External drainage+0.2%CA group to theexogenous bile acid to fill the stomach. After Drainage of7days for70%partialhepatectomy, to establish obstructive jaundice rats following70%partialhepatectomy with different biliary drainages model. And Collect the rats bloodand liver tissue samples after the operation72h. Biochemical analyzer test liver function, Immunohistochemical method to observe the liver tissue PCNAexpression、Mitotic index, ELISA kits detect total bile acid levels, TUNELmethod determination of liver cell apoptosis index,Immunohistochemicalmethod to observe the liver Bax and Bcl-2expression.Results:（1）After PH, The mortality rates ID group and ED+CA group had nostatistics significance Compared with the SH group，But it significantly lowerthan in OJ group and ED group.（2）After PH72h Liver regeneration rate、PCNA、Mitotic index, ID group was higher than ED group(P<0.05), ED groupwas higher than OJ group(P<0.05), ID group and ED+CA group had nostatistics significance Compared with the SH group.（3）the levels of TBA in OJgroup was significantly higher than other groups (P<0.01), After PH72h, Thehighest OJ group of the levels of TBA, ID group was higher than EDgroup(P<0.05), ID group and ED+CA group had no statistics significanceCompared with the SH group.（4）OJ group of apoptotic cells increasedsignificantly, SH group only a small amount of cell apoptosis,ID group、ED+CA group、ED group Apoptosis index rose in turn, OJ group、ID group、EDgroup、SH group Apoptosis index compared with each other are statisticallysignificant（P＜0.05）, ID group and ED+CA group had no statisticssignificance Compared with each other.（5）OJ group and ED group expressvolume increased significantly, The expression of ED group lower than the OJ group (p<0.05), OJ group、ID group、ED group、SH group Apoptosis indexcompared with each other are statistically significant（P＜0.05）. The expressionof BaxConsistent with the apoptosis index. The expression of Bcl-2Increase inID group and ED+CA group, Compared with SH group was statisticallydifference（P＜0.05）ID group and ED+CA group had no statistics significanceCompared with the SH group.Conclusions:1Both internal and external drainage can release biliary obstruction, the liverregeneration after internal drainage is better improved than external drainageand no drainage. External drainage has obvious inhibition on liverregeneration.2The difference of liver regeneration between ID group and ED group may bedue to the enterohepatic circulation was damaged and the Liver cellapoptosis increases thus affects the liver regeneration.3External drainage added exogenous bile acid intervention can achieve thesame effect as the internal drainage, it provides a new direction for clinicaltreatment.