Establishment of a rat model of early-stage liver failure and Th17/Treg imbalance

• Main Authors: LI Dong, LU Zhonghua, GAN Jianhe
• Format: Article
• Language: zho
• Published: Editorial Department of Journal of Clinical Hepatology 2016-05-01
• Series: Linchuang Gandanbing Zazhi
• Online Access: http://www.lcgdbzz.org/qk_content.asp?id=7404

ObjectiveTo investigate the methods for establishing a rat model of early-stage liver failure and the changes in Th17, Treg, and Th17/Treg after dexamethasone and thymosin interventions. MethodsA total of 64 rats were randomly divided into carbon tetrachloride (CCl4) group and endotoxin ［lipopolysaccharide (LPS)］/D-galactosamine (D-GalN) combination group to establish the rat model of early-stage liver failure. The activities of the rats and changes in liver function and whole blood Th17 and Treg were observed to evaluate the effectiveness of the rat model. Dexamethasone and thymosin were used for intervention and related effects were observed. The t-test was used for comparison of continuous data between groups, and the paired t-test was used for comparison of continuous data within one group. ResultsThe serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin showed significant increases in the model groups and were significantly different from those in the control group (CCl4 group: t=-3.95, -3.60, and -3.57, P=0.006, 0009, and 0.009; LPS/D-GalN combination group: t=-10.56, -9.63, and -11.82, all P＜0.001). After the model was established, the rats showed an increase in Th17, a reduction in Treg, and Th17/Treg imbalance. The liver pathology in the rats in the model groups was consistent with the changes in early-stage liver failure. After dexamethasone intervention, the rats showed a reduction in Th17(CCl4 group: 0.830±0.224 vs 0.580±0.105, t=3.25, P=0.014; LPS/D-GalN combination group: 1.301±0.163 vs 0.921±0141, t=4.12, P=0.004), an increase in Treg (CCl4 group: 0.317±0.076 vs 0.385±0.083, t=-11.13, P＜0.001; LPS/D-GalN combination group: 0.351±0.110 vs 0.570±0.119, t=-4.06, P=0.005), and Th17/Treg rebalance (CCl4 group: 2.201±0556 vs 1511±0534, t=356, P=009; LPS/D-GalN combination group: 3699±0976 vs 1619±0423, t=382, P=007) After thymosin intervention, the rats showed an increase in Th17 (CCl4 group: 1161±0219 vs 1270±0230, t=-574, P=0001; LPS/D-GalN combination group: 0451±0095 vs 0929±0130, t=-861, P＜0001), a reduction in Treg (CCl4 group: 0643±0100 vs 0615±0092, t=266, P=0032; LPS/D-GalN combination group: 0200±0085 vs 0161±0095, t=315, P=0016), and aggravation of Th17/Treg imbalance (CCl4 group: 1799±0625 vs 2071±0587, t=-6.47, P＜0.001; LPS/D-GalN combination group: 2.244±0.634 vs 5.770±1.455, t=-11.72, P＜0.001). ConclusionThe two methods of CCl4 and LPS/D-GalN combination can successfully establish the rat model of early-stage liver failure with no deaths, and liver histological results and serum biochemical changes are in consistence with the changes in early-stage liver failure. Dexamethasone intervention helps to improve Th17/Treg imbalance, while thymosin intervention causes aggravation of Th17/Treg imbalance.