急性肝衰竭大鼠血清TNF-α、IL-10水平的动态变化和TNF-α单克隆抗体护肝机制的探讨

Abstract

Objective To observe the dynamic changes of serum TNF-α, IL-10 of rats with acute liver failure and to explore the hepatoprotective efficacy of anti-tumor necrosis factor alpha monoclonal antibody (anti-TNF-α mAb, Infiximab). Methods Fourteen Wistar rats (7 males and 7 females) were divided into control group(n=7) and treatment group(n=7) randomly. All acute liver failure models of rats was established by hypodermic injection with lipopolysaccharides (10 μg/kg) and intraperitoneal injection with D-Galactosamin (800 mg/kg). Then the rats in the control group were injected with saline hypodermically (1 ml/kg), and the rats in the treatment group were given infiximab injection (5 mg/kg). The levels of serum TNF-α, IL-10 of 2 groups were measured by enzyme-linked immunosorbent assay (ELISA) at the 0, 12, 24, 48 and 72 h and were compared by independent sample t-test between 2 groups. The serum TNF-α, IL-10 levels at different time points in the same group were compared using general linear model-repeated analysis. Results The levels of serum TNF-α reached a peak at 12 h in the control group and gradually decreased at 24, 48 and 72 h. The levels of serum IL-10 rose gradually and significantly at 24 h and peaked at 72 h. The levels of IL-10 and INF-α at 72 h showed significant difference compared with other time points (F=257.31, 227.815, 89.276, 9.984; all in P<0.05) . The levels of serum TNF-α in the treatment group showed similar changes as the control group, reached a peak at 12 h and gradually decreased at 24, 48 and 72 h. The levels of serum IL-10 increased evidently at 12 and 24 h, but gradually at 48 and 72 h. The levels of IL-10 and TNF-α at 72 h showed significant difference compared with other time points (F=451.471, 195.105, 26.259, 22.962; all in P<0.05) . Compared with the control group, the TNF-α levels in the treatment group at 12, 24 and 72 h were significantly lower (t=2.392, 3.393, 2.276; all in P<0.05), and the IL-10 levels were higher at 0, 12 and 24 h with significant difference at 12 h (t=-4.556, P=0.002), but lower at 48 and 72 h with significant difference at 72 h(t=7.997, P<0.001). Conclusions Serum TNF-α and IL-10 play import roles in the progression of acute liver failure. A large amount of pro-inflammatory cytokines such as TNF-α are induced at the early phase of acute liver failure, and the anti-inflammatory cytokines as IL-10 are induced at the advanced phase. Anti-TNF-α mAb (Infiximab) may probably alleviate liver injury by antagonizing the TNF-α activity and increasing the expression of IL-10 at the early phase. Key words: Acute liver failure; Rats; Tumor necrosis factor-α; Interleukin-10; Anti-tumor necrosis factor-alpha monoclonal antibody