The effect of the balance between cytokines in the serum of hepatic fibrosis rats on the expression of β-catenin in their livers / 中华传染病杂志

ABSTRACT

Objective To investigate the effect of the balance between helper T lymphocyte (Th) 1 cytokines and Th2 cytokines in the serum of hepatic fibrosis rats induced by CCl4 on the expression of β-catenin in their livers. Methods Seventy-five rats were divided into control group,treatment group and model group. Hepatic fibrosis models were built by subcutaneous injection of CCl4in male Wistar rats, then rats in treatment group were treated with pentoxifylline(PTX) by intragastric administration. The model rats without PTX treatment served as treatment control. The serum levels of Th1 cytokines(interferon-γ, IFN-γ; tumor necrosis factor-α, TNF-α), Th2 cytokines (interleukin-4,IL-4;interleukin-6,IL-6) and type Ⅳ collagen were measured by enzyme-linked immunosorbent assay (ELISA). The expression and distribution of β-catenin in liver tissue and the percentage of area of type Ⅳ collagen accounted in the liver were analyzed by immunohistochemical analyses. The changes in serum cytokines were depicted by using One-way ANOVA, and the correlation between β-catenin expression and cytokines levels or hepatic fibrosis development was elucidated by Bivariate.Results The serum levels of Th2 cytokines in model group were significantly higher than those in treatment group, and even higher than those in control group (F=71. 260,91. 732, all P＜0.05).However, the levels of Th1 cytokines in model group were significantly lower than in treatment group while even lower than those in control group(F= 50. 420,10. 625, all P＜0.05). Serum cytokines came out to be Th2 polarized. Meanwhile, the percentage of type Ⅳ collagen area accounted in the liver,which was corresponding to the degree of liver fibrosis, was lower in the treatment group than the model group and even lower in control group (F=3 000,both P<0.05). β-catenin expression in the liver of model group was stronger than that in the treatment group, and even stronger than that in normal group (F=92. 030, both P＜0. 05). According to β-catenin immunohistochemical analyses based on patho-photos, livers from the model group showed dark color in both cell cytoplasm and nucleus, while the liver from the treatment group only showed weak color in cytoplasm and no straining color in nucleus and the liver from normal group showed colors neither in cytoplasm nor in the nucleus.The expression of β-eatenin had a positive correlation with either the level of Th2 cytokines in serum of rats (r=0. 560,P＜0.01) or the percentage of area of type Ⅳ collagen accounted in the liver of rats (r=0. 757, P＜0. 01). Conclusions Th2 polarization in serum cytokines can aggravate the development of liver fibrosis by inducing the expression of β-catenin, which in the livers of rats is a reflection of the degree of the liver fibrosis.