1,25（OH）2D3通过调节miR-146a水平抑制大鼠肝纤维化的体内和体外观察

doi:10.3969/j.issn.1672-5069.2019.03.006

实用肝脏病杂志 ›› 2019, Vol. 22 ›› Issue (3): 333-336.doi: 10.3969/j.issn.1672-5069.2019.03.006

1,25（OH）₂D₃通过调节miR-146a水平抑制大鼠肝纤维化的体内和体外观察

周丽云, 李校天, 李丽, 杨俊超

314000 浙江省嘉兴市第一医院肝病研究所（周丽云）；
河北工程大学附属医院消化内科（李校天）；
血液内科（李丽，杨俊超）

收稿日期:2018-06-15 出版日期:2019-05-10 发布日期:2019-05-15
通讯作者: 李校天,E-mail：xtianli@sina.com
作者简介:周丽云,女,28岁,住院医师。主要从事慢性肝病诊治的基础与临床研究。E-mail:1071815100@qq.com
基金资助:
河北省卫生与计划生育委员会重点科技研究计划项目（编号20150490）; 河北省研究生创新资助项目（编号171290080015）

1,25（OH）₂D₃ inhibits hepatic fibrosis by regulating miR-146a levels in vitro and in vivo

Zhou Liyun, Li Xiaotian, Li Li

Department of Gastroenterology,Affiliated Hospital,Hebei University of Engineering,Handan 056002,Hebei Province,China

Received:2018-06-15 Online:2019-05-10 Published:2019-05-15

摘要/Abstract

摘要： 目的体内体外观察1,25（OH）₂D₃通过调节miR-146a水平抑制大鼠肝纤维化的作用机制。方法建立CCl₄诱导的大鼠肝纤维化模型,体外转染肝星状细胞（HSCs）miR-146a 模拟剂/抑制剂,观察1,25（OH）₂D₃处理对动物肝组织变化和HSC增殖和凋亡的影响。采用qPCR法检测肝组织miR-146a水平,采用CCK8法检测细胞增殖,使用流式细胞术检测HSC凋亡。结果在干预8 w末,1,25（OH）₂D₃干预组大鼠肝纤维化程度明显减轻; 1,25（OH）₂D₃干预组大鼠肝组织miR-146a水平为（0.70± 0.03）,显著高于橄榄油组【（0.33±0.17,P<0.05）】; 1,25（OH）₂D₃组细胞增殖率为58.8%,较DMSO组下降了15.9%,转染miR-146a 模拟剂组大鼠HSC增殖率为46.5%,较对照组下降了53.3%,转染miR-146a 抑制剂组HSC增殖率为132.8%,较对照物组升高了32.8%（P<0.05）,1,25（OH）₂D₃干预组细胞凋亡率为12.6%,较DMSO组增加了5.2%,转染miR-146a 模拟剂组细胞凋亡率为16.8%,较对照组细胞凋亡率增加了8.2%,转染miR-146a 抑制剂组细胞凋亡率为6.3%,较对照组细胞凋亡率减少了2.2%（P<0.05）,提示1,25（OH）₂D₃具有抑制HSC增殖、促进凋亡作用。结论 1,25（OH）₂D₃可能通过调节miR-146a水平抑制HSC活化和抑制大鼠肝纤维化。

关键词: 肝纤维化, 肝星状细胞, 1, 25（OH）₂D₃, miR-146a, 大鼠

Abstract: Objectiv To observe the inhibitory effect of 1,25（OH）₂D₃ on liver fibrosis in hepatic stellate cells （HSCs） and in rat model. Method The CCl₄-induced liver fibrosis was made in rats,and the activation of HSCs were induced by 10 pmmol/L TGF-β1 incubation. The miR-146a mimic/inhibitor were transfected in HSCs and 1,25（OH）₂D₃ intervention were paralleled. The miR-146a levels in liver tissues were detected by qPCR,the proliferation of cells was measured by CCK8 and the apoptosis was detected by flow cytometry. Results At the end of 8 weeks,the hepatic fibrosis in 1,25（OH）₂D₃ intervention group was significantly milder than that in the control group;the miR-146a level in 1,25（OH）₂D₃ intervention group was significantly higher than in oil control group[（0.70±0.03） vs.（0.33±0.17）,P<0.05];the proliferation rate in1,25（OH）₂D₃ group was 58.8%,15.91% of lower than in DMSO group,in miR-146a mimic transfected group was 46.5%,53.3% of lower than in control,in miR-146a inhibitor group was132.8%,32.8% of higher than in control（P<0.05）;the apoptosis rate of HSCs in1,25（OH）₂D₃ group was 12.6%,5.2% of higher than in DMSO,in miR-146a mimic transfected group was16.8%,8.2% of higher than in control,and in miR-146a inhibitor transfected group was 6.3%,2.2% of lower than in control （P<0.05）,indicating the inhibition of 1,25（OH）₂D₃ on proliferation and promotion on apoptosis of HSCs. Conclusion 1,25（OH）2D3 might modulate miR-146a levels to inhibit liver fibrosis.

Key words: Liver fibrosis, Hepatic stellate cells, 1, 25（OH）₂D₃, miR-146a, Rats

周丽云, 李校天, 李丽, 杨俊超. 1,25（OH）₂D₃通过调节miR-146a水平抑制大鼠肝纤维化的体内和体外观察[J]. 实用肝脏病杂志, 2019, 22(3): 333-336.

Zhou Liyun, Li Xiaotian, Li Li. 1,25（OH）₂D₃ inhibits hepatic fibrosis by regulating miR-146a levels in vitro and in vivo[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 333-336.

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1,25（OH）₂D₃通过调节miR-146a水平抑制大鼠肝纤维化的体内和体外观察

1,25（OH）₂D₃ inhibits hepatic fibrosis by regulating miR-146a levels in vitro and in vivo

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