胶原酶门静脉灌注逆转兔CCl_4性肝硬化

Portal coiiagenase administration reverses carbon tetrachloride-induced rabbit liver cirrhosis

目的:观察门静脉灌注胶原酶对逆转实验性肝硬化的作用．方法:4只兔作为正常对照(A组)给予四氯化碳(CCl4)sc 12 wk,再行门静脉生理盐水灌注 12 wk．另外4只兔先给予CCl4 sc 12 wk,再行胶原酶门静脉灌注12 wk(B组),再有3只兔先行CCl4 sc 12 wk,再行生理盐水门静脉灌注 12 wk(C组)．结果:经过12 wk的CCl4注射和12 wk的门静脉灌注后,应用胶原酶灌注的B组动物肝羟脯氨酸含量显著低于用生理盐水灌注的对照组 (C组)(177．5±35．6μg/g vs 446．3±150．1μg／g; F=13．78,P<0．01)．肝组织学检查也显示胶原酶治疗后肝硬化完全消退．肝、肾、肺、脑、心组织学检查未发现胶原酶的毒性反应．实验中有2只兔发生过敏反应,其中1只死亡．结论:门静脉灌注胶原酶可以促进已形成的肝硬化向正常肝组织结构逆转．

AIM： To investigate whether portal collagenase administration can reverse liver cirrhosis. METHODS： Four normal controls （group A） received olive oil subcutaneously （sc） for 12 weeks followed by normal saline portal perfusion for 12 weeks. Another four rabbits （group B） received carbon tetrachloride （CCl4） sc for 12 weeks and then 6 mg of collagenase portally for 12 weeks, while three control rabbits （group C） received CCl4 for 12 weeks followed by saline for 12 weeks. RESULTS： After 12 weeks of CCl4 and another 12 weeks of portal vein perfusion, liver hydroxyproline content in collagenase-treated rabbits was significantly decreased as compared with that in saline-treated controls （177.5 ± 35.6 μg/g vs 446.3 ± 150.1 μg/g; F = 13.78, P 〈 0.01）. Fur-her, liver histology showed complete regression of cirrhosis in the collagenase-treated animals. No toxicity of liver, kidney, lung, brain or heart was observed histologically. Anaphylaxis occurred in 2 animals and one was fatal. CONCLUSION： Portal administration of collagenase can promote the reversion of established liver cirrhosis in the rabbit CCl4 model.