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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 ) .④肝组织AT1R的表达与肝窦区
OBJECTIVE: To observe the effect of losartan on the expression of angiotensin Ⅱ type 1 receptor (AT1R) in hepatic fibrosis rat model and collagen formation.Methods: The model of hepatic parenchymal damage induced by tetrachloro (CCl4) .Thirty-six Wister rats were randomly divided into three groups: A group (control group), B group (liver fibrosis model group), C group (Losartan intervention group), 12 in each group. All rats except the control group were subcutaneously injected with 400 mL / L of LCCl 4 (refined olive oil formulated once every 3 days for 6 weeks), and the control group was given the same volume of refined olive oil.The losartan group was given Los (Losartan 50mg / kg dissolved in 2mL of distilled water) intragastric administration, 1 times / d, to 6wk.After the experiment, rats were sacrificed to take liver tissue, the use of VG staining of liver tissue collagen expression and fibrosis degree The changes of hepatic sinusoidal ultrastructure, expression of AT1R, type Ⅰ, Ⅲ collagen and type Ⅰ, Ⅲ procollagen gene expression were observed by transmission electron microscopy, indirect immunofluorescence, immunohistochemistry and in situ hybridization. Results: ① Under light microscope, the degree of hepatic fibrosis in group C was significantly lower than that in group B (P <0.05) .② The number of AT1R positive cells in group B was significantly higher than that in group A (P <0.01), and the number of AT1R positive cells in group C was significantly lower than that in group B (P0.01) .③③ Immunohistochemistry and in situ hybridization showed that the average absorbance (IA) values of type Ⅰ, type Ⅲ collagen and type Ⅰ, Ⅲ procollagen mRNA in group B were significantly higher than those in group A (P <0.01, P <0.05), C group was lower than B group (P <0.01, P <0.05) .④The expression of AT1R in liver tissue was positively correlated with the area of hepatic sinusoid