1,25(OH)_2D_3干预IL-17通路抑制大鼠肝纤维化作用机制研究  

Study on the mechanism of 1,25(OH)_2D_3 inhibited hepatic fibrosis with intervention on IL-17 pathway in rats

作　　者：尹燕[1] 李校天[2] 郭永泽[2] 周丽云[3] 王蕾[2] YIN Yan LI Xiaotian GUO Yongze ZHOU Liyun WANG Lei(Chengde Medical College, Chengde 067000 Department of Gastroenterology Department of Pathology, Affiliated Hospital of Hebei University of Engineering, China)

机构地区：[1]承德医学院,河北承德067000 [2]河北工程大学附属医院消化科 [3]河北工程大学附属医院病理科

出　　处：《胃肠病学和肝病学杂志》2017年第9期1011-1015,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：河北省卫生计划生育委员会重点科技研究计划(20150490)

摘　　要：目的通过检测1,25(OH)_2D_3对大鼠肝组织中IL-17及其相关蛋白表达的影响,探讨1,25(OH)_2D_3抑制肝纤维化形成的作用机制。方法将60只大鼠随机分为四组:对照组、模型组(DMN盐溶液)、药物溶剂组(DMN盐溶液+花生油灌胃)、治疗组(DMN盐溶液+1,25(OH)_2D_3油溶液灌胃),8周后对各组大鼠肝脏行Masson染色,观察其病理学变化,并行纤维化程度分级;免疫组化法(IHC)观察各肝组织中IL-17的蛋白表达;Western blotting法定量检测各组肝脏中IL-17、RORγt及MIP3α蛋白表达;Real time-PCR法分析各组肝脏中IL-17、RORγt和MIP3αmRNA表达量。结果模型组及药物溶剂组大鼠肝脏呈显著纤维化改变,1,25(OH)_2D_3治疗组肝脏纤维化程度较溶剂组明显减轻;模型组和药物溶剂组肝组织中IL-17、RORγt、MIP3α蛋白及mRNA表达量较对照组明显升高,而治疗组中三者蛋白及mRNA表达量较溶剂组显著降低,差异均具有统计学意义(P<0.05)。结论1,25(OH)_2D_3抑制肝纤维化发生、发展;1,25(OH)_2D_3可抑制肝组织中IL-17、RORγt及MIP3α蛋白和mRNA表达,从而减轻肝纤维化,提示1,25(OH)_2D_3可能通过干预肝脏IL-17信号通路抑制纤维化进程。Objective To detect the effect of 1,25 （OH） 2D3 on the expression of IL-17 and its associated protein in rat liver tissue, and to investigate the mechanism of 1,25 （OH）2D3 in inhibiting hepatic fibrosis. Methods Sixty rats were randomly divided into 4 groups： control group, model group （DMN solution） , solvent group （ DMN solution ＋ peanut oil by gavage） , treatment group [ DMN solution ＋ 1,25 （OH） 2D3 peanut oil solution orally ] , after 8 weeks treat- ment, Masson staining was used to observe the pathological change liver tissues of rats in each group, the degree of fi- brosis grading was done. Immunohistochemistry （IHC） method was used to observe the expression of IL-17 protein in liver tissue; Western blotting was used to detect expressions of IL-17, RORγt and MIP3α protein; Real time-PCR was used to detect expressions of IL-17, RORγt and MIP3α mRNA. Results The liver fibrosis changes were significant in model group and drug solvent group, liver fibrosis in 1,25 （OH）2 D3 treatment group was significantly reduced than that in solvent group; expressions of IL-17, RORγt and MIP3α protein in model group and drug solvent group were signifi- cantly higher than those in control group （P 〈 0.05 ） , the expressions of three indexes protein and mRNA in the therapy group were significantly lower than those in solvent group （P 〈 0.05）. Conclusion 1,25 （OH）2D3 can inhibite devel- opment process of liver fibrosis; the 1,25 （OH）2D3 can inhibit the expressions of IL-17, RORγt and MIP3α protein and mRNA. 1,25 （OH）2D3 may inhibit the process of fibrosis by interfering with the IL-17 signaling pathway in the liver.

关 键 词：肝纤维化 IL-17 RORΓT MIP3α 1 25(OH)2D3 

分 类 号：R575[医药卫生—消化系统]