[1]袁 瑾,赵 灿,张渭涛.依普利酮通过靶向微小RNA-192和微小RNA-29a/b/c减轻糖尿病肾病模型大鼠肾损伤机制研究[J].陕西医学杂志,2022,51(3):293-297,302.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.007]
　YUAN Jin,ZHAO Can,ZHANG Weitao.Mechanism of eplerenone alleviating renal injury in diabetic nephropathy rat model by targeting miR-192 and miR-29a/b/c[J].,2022,51(3):293-297,302.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.007]
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依普利酮通过靶向微小RNA-192和微小RNA-29a/b/c减轻糖尿病肾病模型大鼠肾损伤机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年3期
页码:
293-297,302
栏目:
基础研究
出版日期:
2022-03-05

文章信息/Info

Title:
Mechanism of eplerenone alleviating renal injury in diabetic nephropathy rat model by targeting miR-192 and miR-29a/b/c
作者:
袁 瑾1; 赵 灿1; 张渭涛2
(1.西安市第一医院肾内科,陕西 西安 710002; 2.西安市第一医院内分泌科,陕西 西安 710002)
Author(s):
YUAN Jin; ZHAO Can; ZHANG Weitao
(Department of Nephrology,Xi'an No.1 Hospital,Xi'an 710002,China)
关键词:
糖尿病肾病;  依普利酮;  微小RNA-192;  微小RNA-29a/b/c;  机制
Keywords:
Diabetic nephropathy;  Eplerenone;  miR-192;  miR-29a/b/c;  Mechanism
分类号:
R 587.2
DOI:
DOI:10.3969/j.issn.1000-7377.2022.03.007
文献标志码:
A
摘要:
目的:探讨依普利酮通过靶向微小RNA(miR)-192和miR-29a/b/c减轻糖尿病肾病(DN)大鼠肾损伤的机制。方法:将30只成年雄性SD大鼠分为对照组、模型组、依普利酮组,每组10只。通过实时定量PCR(RT-qPCR)分析各实验组大鼠肾脏组织中miR-192和miR-29a/b/c的mRNA表达水平。使用血糖仪检测大鼠血糖,并对大鼠整体和肾脏组织样本进行称重。通过相关商用试剂盒检测大鼠尿蛋白、肌酐和血尿素氮的浓度。通过蛋白印迹分析大鼠肾脏组织中转化生长因子β1(TGF-β1)、Ⅰ型胶原蛋白(Col Ⅰ)、α平滑肌肌动蛋白(α-SMA)和Smad家族蛋白3(Smad3)的蛋白表达。通过免疫组化分析大鼠肾脏切片中TGF-β1、Smad3和α-SMA的表达。结果:模型组miR-29a、miR-29b、miR-29c的mRNA表达水平低于对照组,miR-192的mRNA表达水平高于对照组(均P<0.05)。依普利酮组miR-29a、miR-29b、miR-29c的mRNA表达水平高于模型组,miR-192的mRNA表达水平低于模型组(均P<0.05)。模型组体重低于对照组,空腹血糖和肾脏质量/体重高于对照组(均P<0.05)。依普利酮组体重高于模型组,空腹血糖和肾脏质量/体重低于模型组(均P<0.05)。模型组尿蛋白、肌酐和血尿素氮水平高于对照组,而依普利酮组低于模型组(均P<0.05)。三组大鼠GFR比较差异有统计学意义,且模型组低于对照组,依普利酮组高于模型组(均P<0.05)。模型组基底膜变薄,肾小球萎缩,近曲小管损伤,经依普利酮治疗后得到改善。模型组TGF-β1、Smad3和α-SMA平均光密度(MOD)高于对照组,而依普利酮组MOD低于模型组(均P<0.05)。结论:依普利酮通可减轻DN模型大鼠肾损伤,机制与靶向miR-192和miR-29a/b/c表达调控TGF-β1/Smad信号通路有关。
Abstract:
Objective:To investigate the mechanism of eplerenone alleviating renal injury in diabetic nephropathy(DN)rat model by targeting miR-192 and miR-29a/b/c.Methods:Thirty adult male SD rats were divided into control group,model group and eplerenone group,with 10 rats in each group.The mRNA expression of miR-29a/b/c and miR-192 in the kidney of rats in each experimental group were analyzed by RT-qPCR.The blood glucose of rats was measured by blood glucose meter,and the body and kidney tissue samples of rats were weighed.The concentrations of urinary protein,creatinine and blood urea nitrogen were detected by relevant commercial kits.TGF-β1,Col Ⅰ,α-SMA and Smad3 in rat kidney was analyzed by Western blot.TGF-β1,Smad3 and α-SMA expression in rat kidney sections was analyzed by immunohistochemistry.Results:The mRNA expression levels of miR-29a/b/c in the model group were lower than those in the control group,and the mRNA expression level of miR-192 was higher than that in the control group(all P<0.05).The mRNA expression levels of miR-29a/b/c in eplerenone group were higher than those in the model group,and the mRNA expression level of miR-192 was lower than that in model group(all P<0.05).The body weight of the model group was lower than that of the control group,and the fasting blood glucose and renal mass to body weight ratio of the model group were higher than those of the control group(all P<0.05).The body weight of eplerenone group was higher than that of model group,and the fasting blood glucose and renal mass to body weight ratio were lower than those of model group(all P<0.05).The levels of urinary protein,creatinine and blood urea nitrogen in the model group were higher than those in the control group,while those in the eplerenone group were lower than those in the model group(all P<0.05).There was significant difference in GFR among the three groups,and the GFR in the model group was lower than that in the control group,and that in the eplerenone group was higher than that in the model group(all P<0.05).In the model group,basement membrane thinning,glomerular atrophy and proximal convoluted tubule injury were improved after treatment with eplerenone.The mean optical density(MOD)of TGF-β1,Smad3 and α-SMA in the model group were higher than those in the control group,while those in the eplerenone group were lower than those in the model group(all P<0.05).Conclusion:Eplerenone can reduce renal injury in DN rat model.The mechanism is related to targeting the expression of miR-192 and miR-29a/b/c and regulating TGF-β1/Smad signal pathway.

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备注/Memo

备注/Memo:
基金项目:陕西省重点研发计划项目(2021SF-335)
更新日期/Last Update: 2022-03-04