探讨急性肝衰竭大鼠血清肿瘤坏死因子（TNF）-α、白介素（IL）-10水平的动态变化及TNF-α单克隆抗体（英利西单抗）对肝损伤保护作用的可能机制。

Wistar清洁级大鼠14只，雌雄各半，按随机数字表法随机分成对照组及治疗组各7只。每只大鼠给予皮下注射脂多糖（LPS）10 μg/kg及腹腔注射D-氨基半乳糖（D-GalN）800 mg/kg建立急性肝衰竭模型，对照组注射LPS和D-GalN后，皮下注射生理盐水1 ml/kg，治疗组皮下注射英利西单抗5 mg/kg。应用酶联免疫吸附测定（ELISA）方法检测两组大鼠给药后0、12、24、48、72 h的血清TNF-α、IL-10的水平。两组间TNF-α和IL-10的比较采用t检验，组内不同时间点的TNF-α和IL-10比较采用重复测量方差分析。

对照组组内比较：注射药物后12 h血清TNF-α水平达到高峰，24、48、72 h随时间延长呈下降趋势；血清IL-10水平随时间延长逐渐升高，24 h后迅速上升，72 h达到高峰，72 h时间点与其它时间点比较差异均有统计学意义（F=257.31、227.815、89.276、9.984，均为P<0.05）。治疗组组内比较：血清TNF-α变化趋势同对照组，在12 h达到高峰，24、48、72 h呈缓慢下降；血清IL-10水平随时间延长而升高，在12、24 h迅速上升，在48、72 h上升趋势减缓，72 h时间点与其它时间点比较差异均有统计学意义（F=451.471、195.105、26.259、22.962，均为P<0.05）。治疗组与对照组比较：治疗组12、24、72 h时间点的血清TNF-α水平较对照组明显下降（t=2.392、3.393、2.276，均为P<0.05）；治疗组血清IL-10水平在0、12、24 h时间点高于对照组，其中12 h时比较差异有统计学意义（t=-4.556，P= 0.002），在48、72 h时间点低于对照组，其中72 h时间点比较差异有统计学意义（t=7.997，P<0.001）。

TNF-α、IL-10是肝急性衰竭发生发展过程中重要细胞因子，在急性肝衰竭早期产生大量的促炎细胞因子TNF-α，晚期血清抗炎细胞因子IL-10水平升高；英利西单抗可能通过拮抗TNF-α的生物活性，下调TNF-α的水平和早期上调IL-10的水平来保护肝脏，避免肝损伤。

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).

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.

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).

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.