安博维拮抗肝纤维化的实验研究

The experiment study of irbesartan antihepatic fibrosis

目的探讨血管紧张素Ⅱ受体阻断剂安博维对四氯化碳(CCl4)诱导的实验性肝纤维化大鼠纤维化水平的影响。方法大鼠肝实质损伤性纤维化模型由CCl4诱导。36只雄性Wister大鼠被随机分为3组:对照组、模型组及治疗组,每组12只。除对照组外所有大鼠均给予皮下注射40%CCl4(精致橄榄油配制,每3天1次,共6周)。对照组注射等体积的精制橄榄油。治疗组同时给予血管紧张素Ⅱ受体阻断剂灌胃。每天1次,至6周。实验结束后处死大鼠收取肝组织及血清标本。利用HE和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(LN),透明质酸(HA),Ⅲ型前胶原(PCⅢ)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受体阻断剂安博维可显著降低肝纤维化大鼠血清LN,HA,PCⅢ及Ⅳ型胶原水平,并显著改善肝纤维化程度(P<0.05)。结论安博维对CCl4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 1 receptor blocker irbesartan on fibrosis level of experimental liver fibrosis in rats. Methods 36 male Wister rats were separated into three groups （control, model and treatment groups）. All rats except those in the control group were given subcutaneous injection of 40% carbon tetrachloride （once every 3 days for 6 weeks ）. Rats in the treatment group were also given 50 mg/kg of irbosartan daily for 6 weeks via gastrogavage. At the end of sixth week, all rats were sacrificed . HE and VG collagen staining were used to evaluate the degree of liver fibrosis. Radioimmtmoassay was performed to determine the serum levels of Laminin（LN）, Hyaiuronic acid （HA）, Procollagen type Ⅲ（PC Ⅲ）, and collagen type Ⅳ. Results Compared with model group, irbesartan significantly reduced the serum levels of LN, HA, PCm and collagen type Ⅳ, and greatly attenuated the degree of liver fibrosis（ P 〈 0.05）. Condusion Irbesartan can greatly protect from liver fibrosis in rats induced by CCl4.