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*

doi:10.3969/j.issn.1672-5069.2017.02.006

摘要/Abstract

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-1α mRNA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。

关键词: 肝纤维化, 1, 25-二羟维生素D3, 缺氧诱导因子, 髓系细胞触发受体-1 , 大鼠

Abstract: Objective To study the effect of 1，25-dihydroxyvitamin D3[1，25（OH）2D3] on hepatic hypoxia inducible factor（HIF） and myeloid cell triggering receptor-1（TREM-1） expression in rats with liver fibrosis and to investigate the protective effect of 1，25（OH）2D3 in this process.Methods 48 male SD rats were randomly divided into TREM-1 knockout，model，1，25（OH）2D3-intervened and control group. The model was established by 0.5%DMN intraperitoneal injection for 8 weeks，and the rats in TREM-1 gene knockout group had the related gene knockout by using iRNA method. The rats in different groups were given 1，25（OH）2D3 and peanut oil solution or peanut oil solution alone gavage. After 8 weeks，the rats were executed under anesthesia，and liver pathological examination were done by routine HE and Masson staining. The hepatic HIF-1 alpha and TREM-1 protein and their mRNA were detected by immunohistochemical and RT-PCR techniques，respectively.Results At the end of eighth week，the hepatic fibrosis in rats in model group was significantly serious than in the control group，while the fibrotic scores in TREM-1 gene knockout group and 1，25（OH）2D3-intervened group（4.216±0.328，6.301±1.625，respectively） were significantly lower than in the model（14.417±3.019，P＜0.05）；the HIF-1α expression were（146.183±6.913，132.804±6.281，respectively），much lower than in the model（105.226±5.374，P＜0.05）；there was no hepatic 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.

Key words: Liver fibrosis, Hypoxia inducible factor-1α, Myeloid cell triggering receptor-1, 1, 25-dihydroxy vitamin D3, Rats

尹燕，李校天，郭永泽，周丽云. 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*[J]. 实用肝脏病杂志, 2017, 20(2): 148-152.

Yin Yan，Li Xiaotian，Guo Yongze，et al.. Effect of 1，25-dihydroxy vitamin D3 on hepatic expression of HIF-1 and TREM-1 in rats with DMN-induced liver fibrosis[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(2): 148-152.

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