茵陈提取物对糖尿病大鼠肾组织中miRNAs表达谱的影响及其肾脏保护作用

doi:10.13481/j.1671-587x.20180307

吉林大学学报(医学版) ›› 2018, Vol. 44 ›› Issue (03): 493-498.doi: 10.13481/j.1671-587x.20180307

茵陈提取物对糖尿病大鼠肾组织中miRNAs表达谱的影响及其肾脏保护作用

孙成博¹, 孙波¹, 刘春禹², 李星儒¹, 王志琴¹, 张璟祎¹, 张雪绵¹, 王泽红¹, 于晓艳¹

1. 吉林大学药学院实验药理与毒理学教研室, 吉林长春 130021;
2. 吉林省中医院针灸科, 吉林长春 130021

收稿日期:2017-08-13 出版日期:2018-05-28 发布日期:2018-05-31
通讯作者: 于晓艳,副教授,硕士研究生导师(Tel:0431-85619702,E-mail:yuxy@jlu.edu.cn) E-mail:yuxy@jlu.edu.cn
作者简介:孙成博(1991-),男,山东省潍坊市人,医学硕士,主要从事中药药理学方面的研究。
基金资助:
吉林省科技厅科技发展计划项目资助课题（20160101206JC，20160414026GH）；吉林省教育厅"十三五"科技项目资助课题（JJKH20180243KJ）；吉林大学大学生创新创业训练计划资助课题（2017A73347）

Effect of herba artemisiae capillaris extracts on expression profile of miRNAs in kidney tissue of diabetic rats and its protective effect on kidney

SUN Chengbo¹, SUN Bo¹, LIU Chunyu², LI Xingru¹, WANG Zhiqin¹, ZHANG Jingyi¹, ZHANG Xuemian¹, WANG Zehong¹, YU Xiaoyan¹

1. Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun 130021, China;
2. Department of Acupunture, Jilin Provincial Traditional Chinese Medicine Hospital, Changchun 130021, China

Received:2017-08-13 Online:2018-05-28 Published:2018-05-31

摘要/Abstract

摘要： 目的：观察茵陈提取物（HACE）对糖尿病大鼠肾组织中微小核糖核酸（miRNAs）表达谱的影响，从miRNA角度探讨HACE对糖尿病大鼠的肾脏保护作用及其机制。方法：采用链脲佐菌素（STZ）复制糖尿病大鼠模型，将60只雄性Wistar大鼠分为对照组（12只）、模型组（24只）和HACE组（24只）。分别于给药8和16周后检测各组大鼠尿白蛋白排泄率和尿蛋白排泄率；HE染色检测大鼠肾组织形态表现；miRNA芯片初步筛查各组大鼠肾组织中miRNAs差异表达谱，对于差异表达在1.74倍以上高丰度的miRNAs筛选阳性miRNAs，采用RT-qPCR验证筛选的miRNAs的相对表达量。结果：与模型组比较，给药8和16周后HACE组大鼠肾小球系膜聚集等现象明显减轻，尿白蛋白排泄率明显降低（P<0.05）。miRNA芯片初筛，对照组和模型组大鼠肾组织中有35个差异表达的miRNAs，模型组和HACE组大鼠肾组织中有17个差异表达的miRNAs。RT-qPCR法检测，给药8周后，与对照组比较，模型组大鼠肾组织中miR-1306-3p（P<0.05）、miR-672-5p（P<0.05）和miR-3550（P<0.01）相对表达量明显降低；与模型组比较，HACE组大鼠肾组织中miR-672-5p相对表达量升高（P<0.05）。给药16周后，与对照组比较，模型组大鼠肾组织中miR-21-5p相对表达量升高（P<0.01），miR-1306-3p（P<0.05）、miR-672-5p（P<0.01）和miR-466d（P<0.05）相对表达量降低；与模型组比较，HACE组大鼠肾组织中miR-21-5p（P<0.05）和miR-1306-3p（P<0.05）相对表达量降低，miR-672-5p相对表达量升高（P<0.05）。结论：HACE作用后糖尿病大鼠肾组织中miRNAs表达谱出现变化。HACE对糖尿病大鼠的肾脏具有保护作用，其机制可能与miRNAs有关。

关键词: 糖尿病肾病, 微小核糖核酸, 表达谱, 茵陈提取物

Abstract: Objective: To observe the effect of herba artemisiae capillaris extracts (HACE) on the expression profile of microRNA (miRNAs) in the kidney tissue of the diabetic rats,and to explore the protective effect of HACE on the kidney tissue of diabetic rats from the miRNA angle. Methods: A total of 60 male Wistar rats were divided into control group (n=12),model group (n=24) and HACE group (n=24).The urinary albumin excretion rate and urinary protein excretion rate of the rats in various groups were detected. HE staining was used to detect the morphology of the kidney tissue of the rats in various groups after treated for 8 and 16 weeks; miRNAs chips were used to screen the expressions of miRNAs in the kidney tissue of the rats.The positive miRNAs were screened out from those with differentially expression amounts higher than 1.74 times as well as high abundance,and RT-qPCR was used to verify the relative expression amounts of miRNAs. Results: Compared with model group,the glomeruli matrix accumulation of the rats in HACE group(after treated for 8 and 16 weeks) was significantly improved and the urinary albumin excretion rates were decreased(P<0.05).The miRNAs chips results showed that there were 35 differentially expressed miRNAs in control and model groups and there were 17 differentially expressed miRNAs in model and HACE groups. The RT-qPCR results showed that after treated for 8 weeks, compared with control group,the relative expression amounts of miR-1306-3p(P<0.05),miR-672-5p(P<0.05) and miR-3550(P<0.01) in the kidney tissue of the rats in model group were decreased;compared with model group,the relative expression amount of miR-672-5p in the kidney tissue of the rats in HACE group was increased (P<0.05).After treated for 16 weeks,compared with control group,the relative expression amount of miR-21-5p in the kidney tissue of the rats in model group was increased(P<0.01),the relative expression amounts of miR-1306-3p(P<0.05),miR-672-5p(P<0.01) and miR-466d(P<0.05) were decreased;compared with model group,the relative expression amounts of miR-21-5p(P<0.05) and miR-1306-3p(P<0.05) in the kidney tissue of the rats in HACE group were decreased,and the relative expression amount of miR-672-5p was increased(P<0.05). Conclusion: The miRNAs expression profile in kidney tissue of diabetic rats were changed after HACE treatment.HACE has the protectively effect on the kidney tissue of diabetic rats and the mechanism may be associated with miRNAs.

Key words: microRNAs, diabetic nephropathy, herba artemisiae capillaris extracts, expression profile

中图分类号:

R587.2

孙成博, 孙波, 刘春禹, 李星儒, 王志琴, 张璟祎, 张雪绵, 王泽红, 于晓艳. 茵陈提取物对糖尿病大鼠肾组织中miRNAs表达谱的影响及其肾脏保护作用[J]. 吉林大学学报(医学版), 2018, 44(03): 493-498.

SUN Chengbo, SUN Bo, LIU Chunyu, LI Xingru, WANG Zhiqin, ZHANG Jingyi, ZHANG Xuemian, WANG Zehong, YU Xiaoyan. Effect of herba artemisiae capillaris extracts on expression profile of miRNAs in kidney tissue of diabetic rats and its protective effect on kidney[J]. Journal of Jilin University Medicine Edition, 2018, 44(03): 493-498.

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茵陈提取物对糖尿病大鼠肾组织中miRNAs表达谱的影响及其肾脏保护作用

Effect of herba artemisiae capillaris extracts on expression profile of miRNAs in kidney tissue of diabetic rats and its protective effect on kidney

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