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目的探讨血管紧张素Ⅱ型受体阻断剂对四氯化碳（CC1_4）诱导的实验性肝纤维化大鼠血清层粘连蛋白等细胞外基质水平的影响。方法大鼠肝实质损伤性纤维化模型CC1_4诱导。50只雄性SD大鼠被随机分为5组：对照组、模型组及治疗组（高、中、低剂量组）、每组10只。除对照组外所有大鼠均给予皮下注射40％CC1_4（精制橄揽油配制，每3日1次，共6周）。对照组注射等体积的精制橄揽油。治疗组同时给予血管紧张素Ⅱ受体阻断剂灌胃。每日1次，至6周。实验结束后处死大鼠收取肝组织、血清标本。利用VG染色对肝组织胶原表达及纤维化程度进行评价。血清学检测包括层粘连蛋白、透明质酸、Ⅲ型前胶原及Ⅳ型胶原检测（放射免疫法）。结果与模型组相比，血管紧张素Ⅱ受体阻断剂可显著降低肝纤维化大鼠血清LN、HA、PCⅢ及Ⅳ型胶原水平。模型组和治疗组（高剂量组）HA（μg／L）分别为911.66±345.49和425.05±115.80,PCⅢ（μg／L）分别为爿31.82±6.90和22.78±8.38,LN（μg／L）分别为209.87±91.57和83.56±22.12，Ⅳ型胶原（μg／L）分别为54.09±19.81和30.51±12.39，并显著改善肝纤维化程度（P＜0.05）。结论科索亚对CC1_4诱导的大鼠肝纤维化有良好的防治作用。
Objective To investigate the effects of angiotensin Ⅱ type receptor blockers on extracellular matrix levels of serum laminin and other factors in experimental hepatic fibrosis rats induced by carbon tetrachloride (CC1_4). Methods Induction of CC1_4 in rat hepatic parenchymal fibrosis model. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: control group, model group and treatment group (high, medium and low dose groups), 10 in each group. All rats except the control group were given subcutaneous injection of 40% CC1_4 (refined olive oil preparation, once every 3 days for 6 weeks). The control group was injected with an equal volume of refined olive oil. The treatment group also given angiotensin Ⅱ receptor blocker intragastrically. Once daily, up to 6 weeks. After the experiment, rats were sacrificed to collect liver tissue and serum samples. VG staining was used to evaluate the hepatic collagen expression and fibrosis. Serological tests include laminin, hyaluronic acid, type III procollagen and type IV collagen (radioimmunoassay). Results Compared with the model group, angiotensin Ⅱ receptor blocker could significantly reduce the level of serum LN, HA, PC Ⅲ and Ⅳ collagen in rats with hepatic fibrosis. The HA (μg / L) of the model group and the treatment group (high dose group) were 911.66 ± 345.49 and 425.05 ± 115.80 respectively, and the PCⅢ (μg / L) were respectively 爿 31.82 ± 6.90 and 22.78 ± 8.38 (209.87 ± 91.57 and 83.56 ± 22.12), collagen type Ⅳ (μg / L) were 54.09 ± 19.81 and 30.51 ± 12.39 respectively, and significantly improved the degree of liver fibrosis (P <0.05). Conclusion Kostia has a good preventive and therapeutic effect on CC1_4-induced hepatic fibrosis in rats.