1,25-二羟维生素D3对肝纤维化大鼠肝组织HIF-1α和TREM-1表达的影响

摘要

目的 通过研究1,25-二羟维生素D3[1,25(OH)2D3]对肝纤维化大鼠肝组织缺氧诱导因子(HIF-1α)和髓系细胞触发受体-1(TREM-1)表达的影响,探讨1,25(OH)2D3抑制肝纤维化进程的作用机制.方法 将48只雄性SD大鼠随机分为TREM-1基因敲除组、模型组、1,25(OH)2D3干预组和对照组.采用iRNA法对其中一组大鼠进行TREM-1基因敲除.采用0.5%二甲基亚硝胺(DMN)腹腔注射连续8周,诱导大鼠肝纤维化模型.其中1组在制备肝损伤模型的同日,给予1,25(OH)2D3花生油溶液灌胃,模型组和对照组给予等量的花生油灌胃.8周后行肝组织学检查,采用免疫组织化学法和RT-PCR法分别检测肝组织HIF-1α和TREM-1蛋白表达及其mRNA水平.结果 在第8 w末,模型组大鼠肝纤维化程度明显重于对照组,而TREM-1基因敲除组和1,25(OH)2D3干预组大鼠肝纤维化计分(4.216±0.328、6.301±1.625)明显低于模型组(14.417±3.019,P<0.05),差异有统计学意义;TREM-1基因敲除组和1,25(OH)2D3干预组肝组织HIF-1α蛋白表达水平(146.183±6.913、132.804±6.281)显著低于模型组(105.226±5.374,P<0.05);TREM-1基因敲除组肝组织无TREM-1蛋白表达,而1,25(OH)2D3干预组肝组织TREM-1表达量(127.386±6.021)显著低于模型组(113.093±5.257,P<0.05),差异均有统计学意义;TREM-1基因敲除组和1,25(OH)2D3干预组肝组织HIF-1αmRNA水平(0.813±0.097、0.824±0.101)显著低于模型组(1.136±0.142,P<0.05);1,25(OH)2D3干预组肝组织TREM-1 mRNA水平(0.986±0.124)明显低于模型组(1.319±0.343,P<0.05),差异均有统计学意义.结论 TREM-1参与肝纤维化的发生发展,而1,25(OH)2D3可能通过抑制HIF-1α和TREM-1的表达而起到抗肝纤维化的作用.%TREM-1 expression in TREM-1 gene knockout group,while its expression(127.386±6.021) in 1,25(OH)2D3 group was much lower than in the model (113.093±5.257,P<0.05);the hepatic HIF-1α mRNA levels in TREM-1 gene knockout and 1,25 (OH)2D3 group (0.813±0.097,0.824±0.101,respectively) were much lower than in the model (1.136 ±0.142,P<0.05);the hepatic TREM -1 mRNA level in 1,25(OH)2D3 group (0.986 ±0.124) was significantly lower than in the model(1.319±0.343,P<0.05). Conclusion TREM-1 participates in the occurrence and development of liver fibrosis,and 1,25 (OH)2D3 may play an antifibrotic role by inhibiting the expression of TREM-1 and HIF-1.