Effect of liver natural killer cells on liver fibrosis in mice with obstructive jaundice

Abstract

Objective To observe the effect of liver natural killer (NK) cells on a liver fibrosis in mice with obstructive jaundice. Methods Mice were randomly divided into 4 groups with 20 mice in each group: group A, operation + Poly I∶C group; group B, operation + phosphate buffered solution (PBS) group; group C, sham-operation + Poly I∶C group; group D, sham-operation + PBS group. Operation groups underwent common bile duct ligation (BDL) to establish obstructive jaundice models and sham-operation groups only underwent dissociation of common bile duct. Poly I∶C was injected to activate and induce the accumulation of NK cells in mouse liver. All the mice were sacrificed at day 14 after operation. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) were determined, and the liver tissue received hematoxylin and eosin (HE) stain and Masson stain. The levels of alpha-smooth muscle actin (α-SMA) was detected by histopathologic method. The liver NK 1.1, α-SMA, and tumor necrosis factor-α (TNF-α) mRNA expression was analyzed by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). Results As compared with group B [(508.69±102.46), and (486.20±126.80) U/L] at day 14 after BDL, the serum ALT and AST levels were significantly increased in group A [(829.78±79.33), and (752.00±67.90) U/L]. The results of HE stain and Masson stain showed that the degree of liver fibrosis in the group A was more severe than that in the group B. The liver histopathologic scores of α-SMA in each group were as follows: group A (+ + + ), group B (+ + ), group C (+ ), group D(+ ). As compared with group C (91.86±5.95, 1.21±0.31, and 1.51±0.03) and group D (1.01±0.03, 1.00±0.00, and 0.99±0.02), the expression levels of NK1.1, α-SMA, and TNF-α mRNA in group A (181.79±13.68, 239.67±12.09, and 12.39±0.87) and group B (168.69±12.90, 179.96±20.95, and 7.44±0.66) were significantly increased (P=0.032, P=0.030). As compared with group D, the expression of NK1.1 mRNA in group C was increased (P=0.029, P=0.031, P=0.027). Conclusion Poly I∶C activated and induced accumulation of NK cells in mouse livers, which aggravated liver fibrosis in mice with obstructive jaundice. Key words: Obstructive jaundice; Natural killer cells; Liver fibrosis