水蛭对肺纤维化大鼠PAI-1的影响

目的:观察水蛭对肺纤维化大鼠纤溶酶原激活物抑制因子-1(Plasminogen activator inhibitor-1,PAI-1)的作用,并探讨其机制。方法:采用气管内注入博莱霉素(BLM)制作大鼠肺纤维化模型,造模后随机分为模型组(MD组,生理盐水6 ml/d灌胃),水蛭组[HD组,水蛭粉4 g/(kg.d)灌胃],另设鼠龄、体重相匹配的正常对照组(NC组),每组8只;28 d后ELISA法测定血浆PAI-1含量及活性,同时检测肺组织羟脯氨酸(HYP)含量。结果:NC组PAI-1含量(0.469 2±0.081 3)μg/L,活性(0.363 4±0.047 0)Au/ml,明显低于MD组和HD组(P<0.01);MD组PAI-1含量(8.920 5±1.094 8)μg/L,活性(2.066 7±0.598 6)Au/ml,高于HD组(3.479 8±0.487 2)μg/L、(1.225 3±0.199 4)Au/ml(P<0.01);NC组、HD组HYP低于MD组(P<0.01)。结论:水蛭可能通过减少凝血酶在肺内的表达,抑制PAI-1生成及活性,使重组尿激酶型纤溶酶原激活物(Urokinase plasmino-gen activator,uPA)活性升高,减少纤维蛋白沉积,对肺纤维化大鼠肺组织具有保护作用。

Effects of Hirudo on the Expression of Plasminogen Activator Inhibitor-1 in Rats with Pulmonary Fibrosis

Objective: To investigate the effects of hirudo on the expression of plasminogen activator inhibitor-1(PAI-1) in rats with pulmonary fibrosis,and to explore the mechanisms.Methods: The pulmonary fibrosis rat model was established by intratracheal instillation of bleomycin.Model rats were divided into bleomycin group(group MD) and hirudo group(group HD) with 8 rats in each group,and control group(group NC) composed of 8 healthy rats was set up.The rats of group MD were given normal saline 6 ml/d by gavage.The rats of group HD were given hirudo power 4g/(kg·d) by gavage.Plasma PAI-1 level and its activity were detected by ELISA,and hydroxyproline(HYP) contents of lung tissues were detected.Results: The PAI-1 level and its activity in group NC were significantly lower than those in the other two groups(P<0.01).The PAI-1 level and its activity in group MD were higher than those in group HD(P<0.01).The HYP content in group NC and group HD were lower than that in MD group(P<0.01).Conclusions: Hirudo can protect the lung tissue of rats with bleomycin-induced pulmonary fibrosis by decreasing thrombin expression in the lungs,inhibiting PAI-1 generation and its activity,increasing urokinase plasminogen activator(uPA) activity and reducing the fibrous protein deposition.