洛沙坦对肝纤维化大鼠AngⅡ1型受体的表达及胶原形成的影响  

Effects of losartan intervention on regulation of collagen expression by angiotensin Ⅱ type 1 receptor in liver fibrosis rat models

作　　者：王卫卫[1] 杨希山[2] 李旭[2] 王捷[1] 田野[1] 赖晃文[1] 杨传红[1] 赖日权[1] 

机构地区：[1]广州军区总医院消化内科,广东广州510010 [2]第一军医大学消化病研究所,广东广州510515

出　　处：《第四军医大学学报》2004年第13期1175-1178,共4页Journal of the Fourth Military Medical University

基　　金：国家自然科学基金 (30 2 70 61 0 )

摘　　要：目的 :观察洛沙坦对血管紧张素Ⅱ 1型受体 (AT1R)在肝纤维化大鼠模型中的表达及胶原形成作用的影响 .方法 :大鼠肝实质损伤性纤维化模型由四氯化碳 (CCl4)诱导 .36只Wister大鼠随机分为 3组 :A组 (对照组 )、B组 (肝纤维化模型组 )、C组 (洛沙坦干预组 ) ,每组 1 2只 .除对照组外所有大鼠均给予皮下注射 4 0 0mL/LCCl4(精致橄榄油配制 ,每 3日1次 ,共 6wk) .对照组注射等体积的精致橄榄油 .洛沙坦干预组同时给予洛沙坦 (洛沙坦 5 0mg/kg溶于 2mL蒸馏水 )灌胃 ,1次 /d ,至 6wk .实验结束后处死大鼠留取肝组织 ,利用VG染色对肝组织胶原表达及纤维化程度进行评价 .采用透射电镜、间接免疫荧光法、免疫组化、原位杂交等方法观察肝窦区超微结构、肝组织AT1R表达、Ⅰ ,Ⅲ型胶原和Ⅰ ,Ⅲ型前胶原基因表达的变化 .结果 :①光镜下观察 ,C组大鼠肝纤维化程度较B组明显减轻 (P <0 .0 5 ) .②B组大鼠肝组织AT1R阳性表达细胞数显著高于A组 (P <0 .0 1 ) ,C组大鼠AT1R阳性表达细胞数显著低于B组 (P <0 .0 1 ) .③免疫组化和原位杂交显示 ,B组大鼠肝组织Ⅰ ,Ⅲ型胶原和Ⅰ ,Ⅲ型前胶原mRNA的平均吸光度 (IA)值较A组明显升高 (P <0 .0 1 ,P <0 .0 5 ) ,C组较B组降低 (P <0 .0 1 ,P <0 .0 5 ) .AIM: To investigate the expression of angiotensin Ⅱ type 1 receptor (AT1R) and the effects of losartan intervention on the synthesis of collagen. METHODS: Thirty six Wister rats were randomly divided into three groups: healthy control group (A), fibrosis model group ( B ) and fibrosis + losartan intervention group (C ). All rats, except the rats in control group, were given subcutaneous injection of 40% carbon tetrachloride (once every 3 days for 6 weeks). The rats in group C were also given losartan of 10 mg/kg daily for 6 weeks via gastrogarage, respectively. At the end of the sixth week, all rats were sacrificed . Van Giesion collagen staining was used to evaluate the extracellular matrix of the liver tissues and the ultrastructures of liver were observed by electron microscopy. The expression of AT1R was detected by indirect immunofluorescent microscopy and the protein or mRNA expression of collagenⅠ, Ⅲ in liver tissues was observed using immunohistochemistry or in situ hybridization methods. The relative contents of collagenⅠ, Ⅲ and procollagenⅠ, Ⅲ mRNA in liver tissues were calculated by image analyzer. RESULTS: ① Under light microscopy, the fibrotic degrees in group C were significantly lower than those in group B ( P <0.05). ② The AT1R positive cells in group B significantly increased than those in group A ( P <0.01), but in group C they decreased significantly than those in group B ( P <0.01). ③ CollagenⅠ, Ⅲ and procollagenⅠ, Ⅲ mRNA expressions in liver tissues significantly increased in group B than those in group A( P <0.01, P <0.05), but in group C they decreased significantly than those in group B ( P <0.01, P < 0.05). ④ Significantly positive correlations were found between the AT1R and collagenⅠ, Ⅲ expressions ( P <0.01, 0.01), and between the procollagenⅠ, Ⅲ mRNA expressions ( P < 0.01, 0.01). CONCLUSION: Losartan can reduce the collagen expression by inhibiting AngⅡand its receptor AT1R.

关 键 词：洛沙坦 受体 血管紧张素 肝纤维化 胶原 

分 类 号：R575[医药卫生—消化系统]