基于TLR4/NF-κB信号通路沉默miR-21对糖尿病肾病大鼠的干预效果  

Intervention effect of silencing miR-21 on rats with diabetic nephropathy by regulating the TLR4/NF-κB signaling pathway

作　　者：张琳萍[1] 姚筱 朱燕亭 金刚[1] ZHANG Linping;YAO Xiao;ZHU Yanting(Nephrotic Hemodialysis Center,Shaanxi Provincial People’s Hospital,Shaanxi,Xi’an 710068,China;不详)

机构地区：[1]陕西省人民医院肾病血透中心,西安市710068 [2]陕西省人民医院医务处,西安市710068

出　　处：《河北医药》2023年第19期2891-2894,2900,共5页Hebei Medical Journal

基　　金：陕西省自然科学基础研究计划(编号:2021JQ-905)。

摘　　要：目的探究基于Toll样受体4(Toll-like receptor 4,TLR4)/核转录因子-κB(nuclear factor kappa B,NF-κB)信号通路沉默微小RNA-21(MicroRNA-21,miR-21)对糖尿病肾病大鼠的干预效果。方法选取45只大鼠,10只作为空白组,其余35只建立糖尿病肾病模型,最终有30只建模成功,将最终建模成功的30只大鼠分为模型组、上调组和下调组,每组10只。做miR-21转染,将10μl miR-21过表达慢病毒悬液、miR-21沉默慢病毒悬液分别注射于上调组、下调组大鼠胃组织中,空白组、模型组注射同剂量的蒸馏水灌胃,注射24 h后观察大鼠变化。结果与空白相比,模型组、上调组、下调组白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1(interleukin-1,IL-1)、C-C基序趋化因子2(CC chemokine ligand 2,CCL2)、内皮素-1(endothelin 1,ET-1)、结缔组织生长因子(connective tissue growth factor,CTGF)、转化生长因子-β1(transforming the growth factor-β1,TGF-β1)水平、TLR4、NF-κB表达量上升,一氧化氮(nitric oxide,NO)水平下降(P<0.05);与模型组相比,上调组IL-6、IL-1、CCL2、ET-1、CTGF、TGF-β1水平、TLR4、NF-κB表达量上升(P<0.05),NO水平下降(P<0.05),下调组IL-6、IL-1、CCL2、ET-1、CTGF、TGF-β1水平、TLR4、NF-κB表达量下降(P<0.05),NO水平上升(P<0.05);与上调组相比,下调组IL-6、IL-1、CCL2、ET-1、CTGF、TGF-β1水平、TLR4、NF-κB表达量下降(P<0.05),NO水平上升(P<0.05)。结论沉默miR-21可缓解糖尿病肾病大鼠炎性反应、肾纤维化,改善内皮功能,其机制可能与TLR4/NF-κB信号通路被抑制有关。Objective To explore the intervention efficacy of silencing miR-21 on rats with diabetic nephropathy by regulating the toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway.Methods Forty-five rats were selected,involving 10 rats treated with blank control(blank group),and 35 subjected to the modeling of diabetic nephropathy.Finally,30 rats were successfully modelled and randomly divided into model group(oral gavage of isodose distilled water),upregulation group(10μl of suspension of cells transfected with miR-21 overexpression lentivirus injected into rat gastric tissues)and downregulation group(10μl of suspension of cells transfected with miR-21 knockdown lentivirus injected into rat gastric tissues),with 10 in each group.Changes of rats were observed at 24 h after injection.Results Compared with those of blank group,relative levels of interleukin-6(IL-6),interleukin-6(IL-1),C-C motif chemokine ligand 2(CCL2),endothelin 1(ET-1),connective tissue growth factor(CTGF),transforming growth factorβ1(TGF-β1),TLR4 and NF-κB were significantly higher in rats of model group,upregulation group and downregulation group,but the nitric oxide(NO)level was significantly lower(P<0.05).Compared with those of model group,significantly higher levels of IL-6,IL-1,CCL2,ET-1,CTGF,TGF-β1,TLR4 and NF-κB,and significantly lower NO level were detected in rats of upregulation group(P<0.05).The opposite trends were detected in rats of downregulation group than those of model group(P<0.05).Compared with those of upregulation group,significantly lower levels of IL-6,IL-1,CCL2,ET-1,CTGF,TGF-β1,TLR4 and NF-κB,and significantly higher NO level were detected in rats of downregulation group(P<0.05).Conclusion Silencing of miR-21 alleviates inflammatory response and renal fibrosis,and improves endothelial function in rats with diabetic nephropathy by inhibiting the TLR4/NF-κB signaling pathway.

关 键 词：糖尿病肾病 微小RNA-21 TOLL样受体4 核转录因子-ΚB 

分 类 号：R587[医药卫生—内分泌]