Impairment Of Liver Regenration Capacity After Partial Hepatectomy In Rat With Obstructive Jaundice

Objective:To observe the effect of obstructive jaundice (OJ) on rat liver regeneration and to explore the possible mechanism of lipid metabolism regulated by Farnesoid X receptor(FXR), with the establishment of model of partial hepatectomy combined with choledochoduodenostomy after OJ.Methods:Eighty male SD rats were randomly divided into control group and experimental group (bile duct ligation group, BDL group). The day was labeled as Od when rats underwent the second operation while before partial hepatectomy and the observation time points were Id,3d and 7d post-operatively. Overall survival rates in 7d, liver weight, liver weight to body weight ratio, relative liver weight restoration, serum level of ALT, AST, TB, TBA, ALB and triglyceride content of liver tissue were detected. H&E, IHC, TUNEL, Masson staining and Sirius Red staining were used to observe the pathological changes of liver tissue after operation. The expression of FXR and SHP were detected by Western Blot. The expression of IL-6, TNF-α, HGF, TGF-β1 and SREBF were detected by Real Time PCR.Results:(1) The overall survival rate of 7d after operation in BDL group decreased significantly compared with control group (100% VS.48%, P<0.01). (2) In comparison with control group in day 1,3 and 7, relative liver weight restoration in BDL group was significantly lower(P<0.01).(3) Compared with control group in day 0, the level of ALT, AST, TB and TBA of BDL group were significantly higher(P<0.01), whereas the level of ALB decreased significantly (P<0.05). In day 1,3 and 7, the level of ALT, AST of BDL group decreased rapidly, and it was much lower than that of control group(P<0.01). Though the level of TB was much lower than that of pre-operation, it was still higher than that of control group significantly(P<0.01). In day 7, the level of TB in BDL group continued to decrease, and there was no difference between two groups (P>0.05). After operation, the level of ALB in BDL group was always lower than that of control group (P<0.05). (4) Compared with control group, the result of H&E staining in day 0 of BDL group showed that hepatocyte arranged in an unregular pattern, the structure of the liver is not clear, a large number of inflammatory cells infiltrating, plenty of intrahepatic bile duct proliferation and inflammatory cell infiltrating around the bile duct, Masson staining and Sirius Red staining showed that the liver tissue appeared collagen fibers deposition. After choledochoduodenostomy, the inflammation of liver tissue was obviously improved. (5) In comparison with control group, number of PCNA positive and apoptosis liver cells of BDL group was significantly increased in day 0(P<0.01). A significant decrease in number of PCNA positive liver cells was noted, and number of apoptosis liver cells of BDL group was still significantly higher in day 1(P<0.01). The number of the two groups had no statistical significance in day 3(P>0.05), and number of PCNA positive cells in BDL grouo was more than control group in day 7(P<0.01). (6) Compared with control group, the content of triglyceride in the liver tissue of BDL group was significantly lower in Od, 1d,3d and 7d (P<0.01). (7) Compared with control group, the level of TNF alpha, IL-6, HGF and TGF beta 1 mRNA of BDL group increased significantly in day 0 (P<0.01). In addition, the level of TNF alpha, IL-6 continued to decrease after operation and was lower than control group(P<0.01). (8) Compared with control group, the expression of FXR and SHP in BDL group was significantly higher than that in control group in day 0 and 1 (P<0.01), while there was no difference in 3d and 7d between the two groups (P>0.05). The expression of SREBF in BDL group was obviously inhibited in Od, 1d,3d and 7d (P<0.05).Conclusions:Body weight was much lower and the nutritional status was poorer in rat with obstructive jaundice than normal rat. The number of apoptosis liver cells increased in the early stage after partial hepatectomy and the liver function was not much poorer than pre-operation after biliary enteric drainage in rat that was performed 50% parital hepatectomy after bile duct ligation. Liver regeneration was delayed and the proliferation of liver cells was impaired, which leads to impairment of the capacity of liver regeneration. During the process of liver regeneration, the accumulation of lipid droplets in the liver cells disappeared, and the content of triglyceride in the liver decreased significantly. Over-activated FXR signaling-induced triglyceride reduction causes insufficient energy supply and thus may contributes to the impaired liver regeneration capacity after PH under obstructive jaundice.