螺内酯对大鼠肝纤维化及TGFβ_1 TIMP-1表达的作用

Effects of spironolactone on rat liver fibrosis and expression of transforming growth factor β_1 and tissue inhibitor of metalloproteinase-1

目的:探讨醛固酮受体拮抗剂螺内酯对TGFβ1和TIMP-1表达的作用,评价螺内酯的抗纤维化作用. 方法:♂SD大鼠34只,随机分为3组.肝硬化模型组: 400 mL/L CCl4油3 mL/kg,sc,2次/wk;螺内酯组:CCl4 油注射的同时予螺内酯20 mg/(kg/d)灌胃;正常对照组:正常饮食、饮水.光镜下动态观察组织学改变,RT—PCR检测肝组织中TGFβ1和TIMP-1的表达. 结果:10 wk时,螺内酯组肝纤维化级别显著低于肝纤维化模型组(P<0.05);但在13 wk,螺内酯组与肝纤维化模型组相比无显著性差异.肝纤维化时TGFβ1和TIMP-1 mRNA水平与正常组相比显著升高(P<0.05).在10 wk时, 螺内酯组TGFβ1 TIMP-1 mRNA水平与肝纤维化模型组相比有下降的趋势,但无显著性差异. 结论:TGFβ1和TIMP-1在肝纤维化时表达显著增加,螺内酯对肝纤维化有一定程度的抑制作用,但对TGFβ1和TIMP-1 mRNA的表达作用不明显.

AIM: To identify the effects of spironolactone on expressions of transforming growth factor β1 and tissue inhibitor of metalloproteinase-1 and to evaluate the curative effect of spironolactone. METHODS: Thirty four male SD rats were randomly divided into 3 groups: Hepatic fibrosis model group: the rats were injected with 400 mL/L CCl4 3 mL/kg subcutaneously two times a week; Spironolactone group: the rats were injected with 400 mL/L CCl4 3 mL/kg subcutaneously two times a week; Spironolactone equivalent to 20 mg/kg per day was given intragastrically; Normal control group: normal chow. Hepatic tissue was observed with light microscopy to compare histological alterations dynamically. The expression of transforming growth factor β1 and tissue inhibitor of metalloproteinase-1 was detected by RT-PCR. RESULTS: The grades of fibrosis in spironolactone group were less than those in hepatic fibrosis model group at the end of the week 10 (P<0.05). However, at the end of week 13, there was no significant difference between the two groups. The expression of TGFpi and TIMP-1 mRNA was up-regulated when fibrogenesis occurred (P <0.05). Although at the end of week 10 there was an inclination that the levels of TGFβ1 and TIMP-1 mRNA in spironolactone group were less than those in hepatic fibrosis model group, there was no significant difference between two groups. CONCLUSION: The expression of TGFβ1 and TIMP-1 mRNA is up-regulated significantly when fibrogenesis occurs. Spironolactone may have a fibrogenesis-inhibiting effect on CCl4 -induced hepatic fibrosis in some degree. Spironolactone has no significant effect on the expression of TGFβ1 and TIMP-1 mRNA