陈 洁,罗敏虹,陈兴强,张 萌,符薇薇.miRNA-9-5p与NF-κB信号通路在2型糖尿病肾病发病中的作用机制[J].,2019,19(17):3239-3243 |
miRNA-9-5p与NF-κB信号通路在2型糖尿病肾病发病中的作用机制 |
The Role of microRNA9-5p and NF-kappa B Signaling Pathway in the Pathogenesis of Type 2 Diabetic Nephropathy |
投稿时间:2019-03-15 修订日期:2019-04-10 |
DOI:10.13241/j.cnki.pmb.2019.17.008 |
中文关键词: 糖尿病肾病 核转录因子-κB miRNA-9-5p 细胞因子 |
英文关键词: Diabetic nephropathy NF-κB miRNA-9-5p Cell factor |
基金项目:海南省普通医学科研资助项目(14A210072) |
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中文摘要: |
摘要 目的:探讨miRNA-9-5p与NF-κB信号通路在2型糖尿病肾病发病中的作用机制。方法:将80只db/db小鼠随机分为糖尿病肾病组、糖尿病肾病+罗格列酮组、糖尿病肾病+miRNA-9-5p组、糖尿病肾病+阴性对照组,每组20只,分别给予生理盐水、噻唑烷二酮类抗糖尿病药马来酸罗格列酮、miRNA-9-5p、miRNA-9-5p阴性对照核酸,10 μg/d腹腔注射。另将20只健康db/m小鼠作为对照组。观察各组空腹血糖(FBG)、餐后血糖(PBG)、肾脏指数、24h尿量、肾脏组织变化,检测血清NF-κB信号通路关键因子单核细胞趋化因子蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6),及肾脏组织NF-κB mRNA、NF-κB p65蛋白水平。结果:糖尿病肾病组FBG、PBG、24 h尿量均高于对照组,肾脏指数低于对照组(P<0.05)。糖尿病肾病+罗格列酮组和糖尿病肾病+miRNA-9-5p组小鼠FBG、PBG、24 h尿量低于糖尿病肾病组,肾脏指数高于糖尿病肾病组(P<0.05)。糖尿病肾病组小鼠血清MCP-1、TNF-α、IL-6水平,肾脏组织NF-κB mRNA、NF-κB p65蛋白水平均高于对照组(P<0.05)。糖尿病肾病+罗格列酮组和糖尿病肾病+miRNA-9-5p组血清MCP-1、TNF-α、IL-6水平,肾脏组织NF-κB mRNA、NF-κB p65蛋白水平低于糖尿病肾病组(P<0.05)。结论:NF-κB在糖尿病肾病发病中起到重要作用,miRNA-9-5p可以阻断NF-κB信号通路,下调MCP-1、TNF-α、IL-6的表达,抑制糖尿病肾病的发生和发展。 |
英文摘要: |
ABSTRACT Objective: To investigate the role of miRNA-9-5p and NF-κB signaling pathway in the pathogenesis of type 2 diabetic nephropathy. Methods: 80 cases of db/db mice were randomly divided into diabetic nephropathy group, diabetic nephropathy+rosiglitazone group, diabetic nephropathy+miRNA-9-5p group, diabetic nephropathy+negative control group, 20 cases in each group, which were respectively given physiological saline, thiazolidinediones two antidiabetic drugs rosiglitazone maleate, miRNA-9-5p, miRNA-9-5p negative control nucleic acid with 10 μg/d intraperitoneal injection. Selected another 20 cases of healthy db/m mice as the control group. Fasting blood glucose (FBG), postprandial blood glucose (PBG), renal index, 24 h urine volume and renal tissue changes were observed in each group, and detected levels of serum NF-κB signaling pathway critical factor monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and expression of NF-κB mRNA, NF-κB p65 in renal tissue. Results: FBG, PBG, 24h urine volume of diabetic nephropathy group were higher than that of control group, renal index was lower than that of control group (P<0.05). FBG, PBG, 24h urine volume of diabetic nephropathy+rosiglitazone group,diabetic nephropathy+ miRNA-9-5p group were lower than that of diabetic nephropathy group,renal index was higher than that of diabetic nephropathy group (P<0.05). The levels of serum MCP-1, TNF-α, IL-6 and expression of NF-κB mRNA, NF-κB p65in renal tissue in the diabetic nephropathy were higher than control group (P<0.05). The levels of serum MCP-1, TNF-α, IL-6 and expression of NF-κB mRNA, NF-κB p65 in renal tissue of the diabetic nephropathy+rosiglitazone group, the diabetic nephropathy+miRNA-9-5p group were lower than that of in the diabetic nephropathy group (P<0.05). Conclusion: NF-κB plays an important role in the pathogenesis of diabetic nephropathy, miRNA-9-5p can block the signal pathway of NF-κB, down regulate the expression of MCP-1, TNF-α, IL-6, inhibit the occurrence and development of diabetic nephropathy. |
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