己酮可可碱对内毒素休克家兔小肠损伤的保护作用及机制

Protective effect of pentoxifylline on acute intestinal damage in rabbits with endotoxic shock

目的 探讨己酮可可碱 (pentoxifylline ,PTX)对内毒素休克时肠道损害的可能保护作用及机制。 方法 采用家兔内毒素休克模型 2 8只 ,随机分成手术对照组、内毒素休克组和PTX治疗组 ,观察PTX对血浆D -乳酸、小肠微循环灌注量及肠组织生物喋呤、三磷酸鸟苷环水解酶Ⅰ(GTP -CHI)及一氧化氮 (NO)含量的影响。 结果 PTX治疗可显著降低门静脉血D -乳酸含量(P <0 .0 5～ 0 .0 1) ,小肠微循环低灌注状态明显改善 ,肠黏膜损伤评分值比休克组显著下降 (P <0 .0 1)。同时 ,PTX治疗组肠组织生物喋呤降低 ,GTP -CHI活性和NO水平趋于正常对照范围。 结论 内毒素休克早期给予PTX治疗对小肠损伤具有良好保护作用 ,其机制可能与抑制局部组织生物喋呤介导过量NO产生有关。

Objective To investigate protective effect of pentoxifylline (PTX) on acute intestinal damage and its mechanism in rabbits with endotoxic shock. Methods A rabbit model of endotoxic shock was produced by a bolus intravenous injection of lipopolysaccharide (400 μg/kg). All 28 animals were randomly divided into sham-operation, endotoxic shock and PTX treatment groups. Plasma D-lactate contents and intestinal microcirculatory perfusion were determined at 0, 2, 4, and 8 hours respectively. Intestinal tissue samples were also obtained to measure biopterin, guanosine triphosphate cyclohydrolase I (GTP-CHI) as well as nitric oxide levels 8 hours after endotoxin challenge. Results Compared with the endotoxic shock group, treatment with PTX significantly improved intestinal microcirculatory perfusion ( P <0.05-0.01), but decreased plasma D-lactate contents ( P <0.05-0.01) and reduced the histopathological evaluation scores ( P <0.01) in animals secondary to endotoxin challenge. Moreover, tissue biopterin levels were markedly decreased; GTP-CHI, nitric oxide levels tended to baseline values in PTX treatment group. Conclusions These results indicate that PTX has protective effect on endotoxin-induced acute intestinal damage which may be associated with nitric oxide formation its over nitricloxide mediated by local biopterin whch was inhibited by PTX after endotoxic shock.