The Relationship Between FXR And Liver Regeneration Of Obstructive Jaundice Rats Following Partial Hepatectomy With Different Biliary Drainages

Background and Objective:The incidence of hilar cholangiocarcinoma has increased gradually, most of patients arecomplicated with different levels of obstructive jaundice (OJ). The OJ patients may died ofliver faiture after partial hepatectomy (PH) due to the complications, such as infection,septicemia, malnutrition. Previous research shows that preoperative biliary drainage is verynecessary for OJ patients. Our previous research confirms that the internal drainage(ID) issuperior to external drainage(ED) in liver regeneration after PH, the mechanism are unclear.The major difference of ID and ED is whether the bile flow into the intestine, therefore, oneof the major reasons of the differences in liver regeneration after PH following ID and ED isbile acids (BA) metabolism properly. As a signal molecule, BA plays a significant role inregulating BA metabolism, energy metabolism and inhibiting intestine the bacteriaover-proliferation in intestine. Cholesterol7α-hydroxylase (CYP7A1) and farnesoid Xreceptor (FXR) plays a critical role in BA metabolism. In this experiment, through comparingthe differences of BA concentration in serum, CYP7A1and FXR expression in liver of OJrats after PH following ID and ED, we can further investigate the mechanism of thedifferences in liver regeneration between ID and ED.Materials and Methods:Male adult Sprague-Dawley rats were randomly assigned to Four groups: obstructivejaundice (OJ: n=30), sham operation(SH: n=30), internal biliary drainage(ID: n=30) andexternal drainage(ED: n=30). The SD rats model of obstructive jaundice was established by common bile duct ligation and division. After7days, internal and external biliary drainagewere builded in different groups by another operation. The obstructive jaundice SD rats werereceived left and middle lobe hepatectomy(about70%of total liver), and also the SD ratsdrainaged for7days were performed the operation. At0h,4h,12h,24h,48h and72h after PH,the rats were succumbed and the specimens of blood and liver were collected. The levels ofTBIL,TBA in serum were determined, the levels of PCNA expression were determined byimmunohistological technology. RT-PCR was used to quantitate the CYP7A1mRNA and FXRmRNA and Western-Blotting to FXR protein.Results:(1) The mortality rates of rats following PH in ID group were significantly lower than in OJgroup and ED group.(2) After PH, the liver regeneration rates in ID group was higher thanED group after in72h (P<0.01), ED group was higher than OJ group (p<0.05), The differenceof ID group and SH group had no statistics significance (P>0.05).(3) After PH，the expressionof PCNA in all of groups were obviously increased at12h, and got to peak at24h in IDgroup.The expression of and PCNA peaked at48h in OJ group and ED group, and the peakvalues were delayed and significantly lower than the ID group (p<0.05).(4) After PH, thelevels of TBA in OJ group was significantly higher than other groups (P<0.01), and got topeak at24h. The levels of TBA in ED, ID and SH group got to peak at48h, and the peakvalues were lower than OJ group (P<0.05).(5) The expression of CYP7A1mRNA in EDgroup was higher than SH group and ID group in0h (P<0.01), then slowly decreased and gotminimum value at48h, the minimum value was higher than ID group and SH group (p<0.05),ID group and SH group had no statistics significance (P>0.05).(6) The expression ofCYP7A1mRNA in ED group was lower than SH group and ID group in0h (P<0.01), thengradually increased and got peak value at48h, the minimum value was lower than ID groupand SH group (p<0.05), ID group and SH group had no statistics significance (P>0.05).(7) The protein expression of FXR in ED group is lower than other groups (P<0.01)，thengradually increased and got peak value at48h, the peak value was lower than ID group andSH group (p<0.01). ID group and SH group were higher than the other groups significance(P<0.05), and had no statistics significance between them (P>0.05).Conclusions:1Both internal and external drainage can release biliary obstruction, reduce serum bilirubinand mitigate the damage of bilirubin for liver,，but the liver regeneration after internaldrainage is better improved than external drainage and no drainage.2The difference of liver regeneration between ID group and ED group may be due to theEnterohepatic circulation was damaged and decreased expression of FXR, thus impressedliver regeneration.