摘要
目的 CCl4皮下注射建立兔肝硬化动物模型,观察Ⅳ型胶原酶门静脉灌注对肝硬化及肝组织中α-平滑肌动蛋白(α-SMA)表达的影响。方法取雄性新西兰大白兔,采用臀部皮下注射50%CCl4橄榄油0.23ml/kg,每周2次,共12周制作肝硬化动物模型,注射等量橄榄油作为对照。12周后各组动物均建立门静脉给药通路,将已形成肝硬化并门静脉插管成功的33只兔随机分为两组(组1,组2),组1为16只、组2为17只。组1经门静脉给药通路注入0.1%Ⅳ型胶原酶1.5ml,组2注入等量0.9%氯化钠,5次/周,共4周。将造模对照组中门静脉插管成功的30只兔同样随机分为两组(组3,组4),每组15只,处理方法同前。4周后,将各组动物处死后留取肝脏组织,观察其病理学及羟脯氨酸含量变化,标本固定后,行α-SMA免疫组织化学染色,行积分光密度、面密度分析。结果肝硬化动物肝脏α-SMA表达显著增强;门静脉灌注0.1%Ⅳ型胶原酶肝硬化动物肝脏纤维化程度明显降低,羟脯氨酸含量显著降低,但α-SMA表达强度显著增高。结论采用门静脉灌注0.1%Ⅳ型胶原酶可显著降低肝纤维化程度,但α-SMA表达增高,可能与肝脏星状细胞激活有关。
Objective This study was designed to investigate the effect of portal collagenase administration on collagen content in cirrhotic liver and the ɑ-SMA expression induced by CCl4 subcutaneous injections in rabbits.Methods Male New Zealand rabbits were injected 50% CCl4(0.23 ml/kg)subcutaneously at gluteal region twice a week for 12 weeks to induce liver cirrhosis.The rabbits in control group administered same volumes of olive oil.After the portal delivery system(PDS)was established,33 rabbits with established liver cirrhosis were divided randomly into 2 groups.The animals in group 1(n=16)were injected 1.5 ml of 0.1% type Ⅳ collagenase saline solution through PDS.The rabbits in group 2(n=17)received the same volume of 0.9%sodium chloride as controls.The injection was conducted 5 times weekly and continued for 4 weeks.Another 30 animals which were injected with olive oil were similarly divided into group 3(n=15)and group 4(n=15)which underwent the same procedure.All the animals were sacrificed after the last injection,and the livers were removed for histologic examination and hydroxyproline detection.Also ɑ-SMA was observed by immunohistochemistry.The integral optical density and area density were calculated by an imaging analysis system.Results The expression of ɑ-SMA in the cirrhotic liver was remarkedly increased.Portal administration of collagenase significantly attenuated liver cirrhosis and decreased the hydroxyproline content,but the ɑ-SMA expression was increased markedly in liver parenchyma.Conclusions Collagenase portal administration significantly alleviated liver cirrhosis,while the ɑ-SMA expression in liver parenchyma was increased.This may attribute to the enhanced activation of hepatic stellate cells by collagenase treatment.
出处
《中华临床医师杂志（电子版）》
CAS
2011年第8期2217-2222,共6页
Chinese Journal of Clinicians(Electronic Edition)
基金
国家自然科学基金(30670960)
