维生素A和β-胡萝卜素对大鼠肝纤维化的影响

EFFECTS OF VITAMIN A AND β-CAROTENE ON EXPERIMENTAL RAT LIVER FIBROSIS

目的 : 研究β-胡萝卜素对四氯化碳诱导的实验性大鼠肝纤维化的影响及其机制。方法 : SD大鼠随机分为 4组。正常对照组 :给橄榄油溶液 1 ml/kg bw,9w;四氯化碳对照组 :给5 0 %CCl4 橄榄油溶液 1 ml/kg bw,每周两次皮下注射持续 9w;维生素 A和 β-胡萝卜素组 :注射5 0 %CCl4 橄榄油溶液 3 w后 ,分别给以维生素 A0 .1 g/kg bw,每周两次皮下注射 ,β胡萝卜素 1 5 0mg/kg bw,每周两次灌胃 ,持续 6 w,之后观察肝脏组织病理及超微结构 ;羟脯氨酸含量和 型胶原 RNA的表达水平。结果 : 1 .普通病理切片显示 ,各治疗组中无明显肝细胞损害 ,纤维化程度计分明显低于四氯化碳对照组 (P<0 .0 5 ) ;超微结构显示维生素 A组的星形细胞中的脂滴数量明显多于正常对照和四氯化碳对照组 ;而β-胡萝卜素治疗组中脂滴数量多于四氯化碳对照组 ;治疗组间质中的胶原纤维亦明显减少 ;2 .治疗组羟脯氨酸含量亦明显低于四氯化碳对照组 (P<0 .0 5 ) ;3 .治疗组中的 型 α2 胶原的 RNA表达水平亦低于四氯化碳对照组。结论 : 维生素 A0 .1 g/kgbw每周两次皮下注射 ,持续 6 w和 β-胡萝卜素 1 5 0 mg/kg bw,每周两次灌胃 ,持续 6 w能降低由四氯化碳诱导的大鼠肝纤维化的程度 ,其作用途径可能与抑制肝脏星形细胞中的脂滴丢失有关?

Objective: To study the effect of vitamin A and β-carotene on rat iver fibrosis induced by carbon tetrachloride (CCl 4) and the mechanism. Methods: The SD rats were divided to 4 groups. 1.Normal group: olive oil 1 ml/kg bw subcutaneous injection twice a week for 9 w; 2.CCl 4 group: 50% CCl 4 olive oil 1 ml/kg bw subcutaneous injection twice a week for 9 w; 3.β-carotene group: after being treated with CCl 4 for 3 w, β-carotene 150 mg/kg bw oral feeding twice a week for 6w. 4.Vitamin A group: after being treated with CCl 4 for 3 w, vitamin A 0.1 g/kg bw subcutaneous injection for 6 w. The liver pathological and ultrastructural change, the content of rat liver hydroxyproline and the type Ⅰ collagen RNA expression were observed. Results: 1.In the treated groups there was no significant liver damage and the fibrosis score was lower than the CCl 4 group (P<0.05). The ultrastructural change was that in the vitamin A treated group the retinol ester droplets in hepatic stellate cells were more than normal control and CCl 4 group, in the carotene group the retinol ester droplets were less than the normal control but more than the CCl 4 group and the interstitial collagen fiber was less than the CCl 4 group significantly. 2.The content of hydroxyproline (HYP) in the treated group was decreased significantly than that in the CCl 4 control group. 3.The value of type Ⅰ (α 2) collagen expression in the treated group was less than those in the CCl 4 group. Conclusion: The dosage of vitamin A (0.1 g/kg bw subcutaneous injection twice a week for 6 w) and β-carotene (150 mg/kg bw oral feeding twice a week for 6 w) can reduce the severity of rat liver fibrosis significantly by inhibiting the loss of retinyl ester droplets from the hepatic stellate cells.