miR-133b在紫檀芪抑制肾脏纤维化的作用研究  

Effect of miR-133b on pterostilbene inhibiting renal fibrosis

作　　者：李思睿 赵迅霞[3] 张玲 刘科良 宋斐 王凯 卢冠军[5] 杨晓玲[2,3] 刘志宏 LI Si⁃rui;ZHAO Xun⁃xia;ZHANG Ling;LIU Ke⁃liang;SONG Fei;WANG Kai;LU Guan⁃jun;YANG Xiao⁃ling;LIU Zhi⁃hong(Public Health and Management of Ningxia Medical University,Yinchuan,Ningxia 750004;NHC Key Laboratory of Metabolic Cardiovascular Diseases Research(Ningxia Medical University),Yinchuan,Ningxia 750004;Basic Medical School of Ningxia Medical University,Yinchuan,Ningxia 750004;Sanquan College of Xinxiang Medical University,Xinxiang,Henan 453003;General Hospital of Ningxia Medical Universitu,Yinchuan,Ningxia 750001,China)

机构地区：[1]宁夏医科大学公共卫生与管理学院,宁夏银川750004 [2]国家卫生健康委员会代谢性心血管疾病研究重点实验室(宁夏医科大学),宁夏银川750004 [3]宁夏医科大学基础医学院,宁夏银川750004 [4]新乡医学院三全学院健康管理学院,河南新乡453003 [5]宁夏医科大学总医院,宁夏银川750001

出　　处：《热带医学杂志》2020年第3期309-313,F0003,共6页Journal of Tropical Medicine

基　　金：国家自然科学基金(81760095,81560120);宁夏科技创新领军人才项目(KJT2016009)。

摘　　要：目的探讨miR-133b在紫檀芪(pterostilbene)抑制肾脏纤维化过程中的作用。方法选取ICR小鼠18只,随机分为对照组(皮下注射生理盐水7 mg/kg)、模型组(皮下注射异丙基肾上腺7 mg/kg)与治疗组(模型组基础上腹腔注射紫檀芪10 mg/kg),每组6只。采用HE染色和Masson染色观察小鼠肾脏的病理变化;通过生物信息学分析验证miRNA-133b与下游COL8A2(胶原蛋白VIII型α2链)、COL5A1(胶原蛋白V型α1链)的靶向调控关系;采用荧光定量聚合酶链反应(RT-qPCR)检验miRNA-133b以及胶原蛋白8A2(COL8A2)、胶原蛋白5A1(COL5A1)的mRNA相对表达水平。结果相比对照组,模型组miR-133b表达显著降低(P<0.01);治疗组miR-133b表达明显高于模型组(P<0.05)。通过生物信息学分析发现miR-133b与COL8A2和COL5A1存在潜在靶向结合关系。RT-qPCR显示,相比对照组,模型组COL8A2和COL5A1的m RNA表达水平均明显升高(P<0.01);相较于模型组,治疗组的mRNA水平明显降低(P<0.01)。且COL8A2、COL5A1与miR-133b之间具有显著负相关性(R2=0.689 4、0.780 8,P<0.01)。结论紫檀芪具有改善肾脏纤维化的作用,其机制可能与上调miR-133b表达有关。Objective To explore the role of miR-133 b in the inhibition of renal fibrosis by pterostilbene. Methods Eighteen ICR mouse were randomly divided into negative control group(subcutaneous injection of normal saline 7 mg/kg),model group(subcutaneous injection of isoproterenol 7 mg/kg)and treatment group(model group based on intraperitoneal injection of red sandalwood 10 mg/kg). The pathological changes of mouse renal were observed by HE staining and Masson staining. The targeted regulation relationship between miRNA-133 b and downstream COL8 A2 and COL5 A1 was verified by bioinformatics analysis. The relative expression levels of miRNA-133 b and collagen 8 A2(COL8 A2)and collagen 5 A1(COL5 A1)were examined by Quantitative Real-time PCR. Results Compared with the control group,the expression of miR-133 b was significantly decreased in the model group(P<0.01). The expression of miR-133 b in the treatment group was significantly higher than that in the model group(P<0.05). Bioinformatics analysis revealed a potential targeted binding relationship between miR-133 b and COL8 A2 and COL5 A1;compared with the control group,the mRNA expression levels of COL8 A2 and COL5 A1 in the model group were significantly increased(P<0.01),and the mRNA level of the treatment group was significantly lower than that in the model group(P<0.01). There was a significant negative correlation between COL8 A2,COL5 A1 and miR-133 b(R2=0.689 4,0.780 8,P<0.01). Conclusion Pterostilbene had the effect of improving renal fibrosis,and its mechanism might be related to the up-regulation of miR-133 b expression.

关 键 词：miRNA-133b 紫檀芪 肾脏纤维化 COL8A2 COL5A1 

分 类 号：R692[医药卫生—泌尿科学]