The beneficial effect of aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of cirrhosis
The beneficial effect of aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of cirrhosis
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DOI：
10.1007/s10620-006-9595-1
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发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
Spira, Gadi
中科院分区：
文献类型：
--
作者：
Assy, Nimer;Hussein, Osamah;Spira, Gadi
本研究的目的是检查抗血栓药物阿司匹林和依诺肝素对肝硬化大鼠模型纤维化进展和再生活性的影响，并确定这两种药物对晚期纤维化或已确诊肝硬化接受部分肝切除术的动物是否有益。硫代乙酰胺诱导的肝硬化大鼠接受盐水 (N=10)、阿司匹林 (N=7) 或依诺肝素 (N=11) 为期 5 周的治疗。根据METAVIR评分评估肝纤维化程度。使用 PCNA 免疫染色监测肝再生。与未经治疗的肝硬化对照组相比，阿司匹林治疗组（43%；chi(2) = 54，P < 0.001）和依诺肝素治疗组（36%；chi(2) = 43，P < 0.001）观察到纤维化等级显着改善。术后，与未治疗的肝硬化对照组（3.2 +/- 0.6 mg/dl）相比，阿司匹林（1.4 +/- 0.18 mg/dl；P < 0.01）和依诺肝素（1.8 +/- 0.35 mg/dl；P < 0.05）治疗组的血清总胆红素水平较低。阿司匹林组的肝脏再生活性显着改善（57.3%+/- 6.8%，而未经治疗的肝硬化对照组为 34.2%+/- 7.2%；P < 0.01），但依诺肝素组没有变化。我们的结论是，阿司匹林和依诺肝素有望成为广泛纤维化患者的有效疗法。
The aim of this study was to examine the effect of the antithrombotic drugs aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of liver cirrhosis and to determine if these two drugs are beneficial in animals with advanced fibrosis or with established cirrhosis undergoing partial hepatectomy. Thioacetamide-induced cirrhotic rats received saline (N=10), aspirin (N=7), or enoxaparin (N=11) for a 5-week treatment period. Hepatic fibrosis was assessed according to METAVIR score. Liver regeneration was monitored using PCNA immunostaining. Compared to untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the aspirin (43%; chi(2) = 54, P < 0.001) and enoxaparin (36%; chi(2) = 43, P < 0.001) treated groups. Postoperatively, total serum bilirubin levels were lower in the aspirin (1.4 +/- 0.18 mg/dl; P < 0.01) and enoxaparin (1.8 +/- 0.35 mg/dl; P < 0.05)-treated groups compared to untreated cirrhotic controls (3.2 +/- 0.6 mg/dl). Hepatic regenerative activity was significantly improved in the aspirin group (57.3%+/- 6.8%, versus 34.2%+/- 7.2% in untreated cirrhotic controls; P < 0.01) but unchanged in the enoxaparin group. We conclude that aspirin and enoxaparin hold promise as a useful therapy for patients with extensive fibrosis.