葡聚糖硫酸钠在构建肝纤维化动物模型中的价值探讨

Evaluation the effect of dextran sulfate sodium on the establishment of hepatic fibrosis animal model

目的探讨葡聚糖硫酸钠(DSS)对BALB/C小鼠肝损伤及其纤维化的影响。方法 50只BALB/C小鼠随机分成正常组、对照组和观察组(6、12周),每组10只,对照组小鼠用5%四氯化碳(CCl4)橄榄油溶液诱导肝纤维化模型,观察组小鼠用3.5%DSS灌胃诱导肝损伤及纤维化模型。HE染色观察肝脏病理损伤,Massion染色观察肝脏纤维化情况,改良赖氏法检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)活性,ELISA法检测血清Ⅰ型前胶原羧基端原肽(PⅠCP)和Ⅲ型前胶原肽(PⅢNP)含量,免疫组化检测肝脏α-平滑肌肌动蛋白(α-SMA)表达变化。结果对照组和观察组小鼠各时间段肝脏的病理损伤明显,胶原纤维表达量增多,血清中ALT和AST活性增强、PⅠNP和PⅢNP含量增加,肝内α-SMA表达量增加,上述变化以对照组最明显,观察组12周次之,观察组与对照组比较,差异有统计学意义(P<0.05)。结论 DSS能有效诱导BALB/C小鼠肝纤维化,其诱导机制值得深入研究。

Objective To study the effect of dextran sulfate sodium（ DSS） on the liver injury and fibrosis in mice. Methods Fifty BALB/C mice were randomly divided into the normal group,the control group and the observation group（ 6 and 12 weeks）,10 mice in each sub-group. The hepatic fibrosis mice in control and observation groups were induced by intraperitoneal injection 5% CCl4 and intragastric administration of3. 5% DSS,respectively. The hepatic pathological changes and fibrosis were examined by hematoxylin eosin（ HE） and massion staining,respectively. The serum contents of ALT and AST were assayed by improved reitman method,the serum levels of carboxyterminal propeptide type I precollagen（ PICP） and aminoterminal propeptide type III precollagen（ PIIINP） were tested by ELISA. The expression of alpha smooth muscle actin（ α-SMA） in liver was detected by immunohistochemical method. Results Compared with the normal group,the hepatic pathological injury and expression of collagen fiber were increased,the serum levels of ALT,AST,PICP and PIIINP were enhanced,and α-SMA expression in liver was elevated in both the control and observation groups. The most predominant change of these indexes was in the control group,the following was appeared in the observation group after 12 weeks,and the difference between two groups was statistical significance（ P〈 0. 05）. Conclusion DSS may induce hepatic fibrosis in BALB/C mice,by which mechanism needs to further study in future.