IGF-1R抑制剂对糖尿病肾病小鼠肾间质巨噬细胞浸润、lncRNA-Gm4419表达的影响  

Effects of IGF-1R Inhibitors on Renal Interstitial Macrophages Infiltration and Expression of lncRNA-Gm4419 in Diabetic Nephropathy Mice

作　　者：王延海[1] 张雷明[1] 张瑞星 樊涛[3] WANG Yanhai;ZHANG Leiming;ZHANG Ruixing(The First Affiliated Hospital of Nanyang Medical College,Henan,Nanyang,473058)

机构地区：[1]河南南阳医学高等专科学校第一附属医院血液净化科,南阳473058 [2]河南南阳医学高等专科学校第一附属医院肾脏内科,南阳473058 [3]河南南阳医学高等专科学校第一附属医院放射治疗科,南阳473058

出　　处：《中国中西医结合肾病杂志》2021年第4期296-299,共4页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：2016河南省科技攻关计划项目(No.162102310216)。

摘　　要：目的:探究胰岛素样生长因子1(IGF-1R)受体抑制剂对糖尿病肾病小鼠肾间质巨噬细胞浸润、lncRNA-Gm4419表达的影响。方法:选取60只雄性C57BL/6小鼠,采用随机数字表法分为:空白对照组、模型组和抑制剂组,每组20只。采用腹腔注射链脲佐菌素制成糖尿病肾病(DN)小鼠模型;采用免疫组化和流式细胞仪检测各组小鼠肾间质中CD_(68)^(+)细胞、F4/80^(+)细胞数目;采用蛋白质印迹检测各组小鼠肾脏组织中细胞因子信号转导抑制因子2(SOCS2)、Toll样受体4(TLR4)和IGF-1R的表达;采用RT-PCR检测各组小鼠肾组织中lncRNA-Gm4419及IGF-1R mRNA表达情况。结果:相比空白对照组,模型组小鼠CD_(68)^(+)细胞数目、F4/80^(+)细胞数目、TLR4蛋白相对表达、IGF-1R蛋白相对表达、Gm4419基因相对表达和IGF-1R9基因相对表达均显著升高,SOCS2蛋白相对表达水平显著降低(P<0.05);相比模型组,抑制剂组小鼠CD_(68)^(+)细胞数目、F4/80^(+)细胞数目、TLR4蛋白相对表达、IGF-1R蛋白相对表达、Gm4419基因相对表达和IGF-1R9基因相对表达均显降低高,SOCS2蛋白相对表达水平显著升高(P<0.05)。结论:抑制IGF-1R的表达可以有效抑制糖尿病肾病小鼠肾间质巨噬细胞浸润和lncRNA-Gm4419表达,其作用机制可能与促进SOCS2表达调控相关信号通路相关。Objective:To explore the effects of insulin-like growth factor 1 receptor(IGF-1R)inhibitors on renal interstitial macrophages infiltration and expression of lncRNA-Gm4419 in diabetic nephropathy(DN)mice.Methods:Sixty male C57BL/6 mice were enrolled.They were divided into blank control group,model group and inhibitor group by random number table method,20 cases in each group.Intraperitoneal injection of streptozotocin was conducted to prepare DN mice models.The counts of renal interstitial CD_(68)^(+)cells and F4/80^(+)cells in each group were detected by immunohistochemistry and flow cytometry.Expression of suppressor of cytokine signaling 2(SOCS2),Toll-like receptor 4(TLR4)and IGF-1R in renal tissues of each group was detected by Western blot.Expression of lncRNA-Gm4419 and IGF-1R mRNA in renal tissues of each group was detected by RT-PCR.The pathology changes of renal tissues in each group were observed by hematoxylin-eosin(HE)staining.Results:In inhibitor group,the structures of glomeruli and renal tubules were relatively complete,and there were only mild inflammatory cells infiltration and fibrosis.Compared with blank control group,CD_(68)^(+)cells count,F4/80^(+)cells count,relative expression of TLR4 protein,IGF-1R protein,Gm4419 gene and IGF-1R gene were significantly increased,while relative expression level of SOCS2 protein was significantly decreased in model group(P<0.05).Compared with model group,CD_(68)^(+)cells count,F4/80^(+)cells count,relative expression of TLR4 protein,IGF-1R protein,Gm4419 gene and IGF-1R gene were significantly decreased,while relative expression level of SOCS2 protein was significantly increased in inhibitor group(P<0.05).Conclusion:Inhibiting the expression of IGF-1R can effectively inhibit renal interstitial macrophages infiltration and expression of lncRNA-Gm4419 in DN mice.The action mechanism may be related to promoting SOCS2 expression and regulating related signal pathways.

关 键 词：糖尿病肾病 胰岛素样生长因子1 巨噬细胞 lncRNA-Gm4419 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]