SOCS2在1型糖尿病肾病肾小管上皮细胞间质转分化中的作用  

Role of SOCS2 in renal tubular epithelial mesenchymal transition in type 1 diabetic nephropathy

作　　者：孙翼[1] 高永棣 董蓉[1] 俞佳丽[1] 查艳(指导)[1,2] SUN Yi;GAO Yong-Di;DONG Rong;YU Jia-Li;ZHA Yan(Department of Immunology,Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学免疫学教研室,贵阳550004 [2]贵州省人民医院,贵阳550002

出　　处：《中国免疫学杂志》2019年第19期2391-2395,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金(81760134);黔科合LH字[2014]7003号;贵州省卫计委基金(gzwjkj2014-2-137)资助

摘　　要：目的:研究细胞因子信号传导抑制因子(SOCS)2在1型糖尿病肾病(T1DN)肾小管上皮细胞间质转分化(EMT)的作用。方法:28只雄性C57/BL6小鼠随机分为对照组(n=7)和T1D组(n=21)。T1D组单次空腹腹腔注射链脲佐菌素(STZ)100 mg/kg,48 h后随机血糖测定结果≥16.7 mmol/L,确诊为1型糖尿病(T1D)。建模成功后,将21只T1D小鼠随机分为3组:T1DN组(n=7)、联合组(贝那普利联合胰岛素用药,n=7)、胰岛素组(胰岛素单独用药,Insulin,n=7)。持续给药8周后处死小鼠,收集血清、尿和肾组织,分别进行生化、病理和相关蛋白与mRNA的检测。结果:与对照组[(3.81±0.24)mmol/L,(32±4.68)μg/24 h]相比,T1DN组血糖、尿蛋白[(21.70±2.26)mmol/L,(286±42.41)μg/24 h]均明显增高(P<0.001),联合组血糖、尿蛋白[(11.84±0.69)mmol/L,(173±17.83)μg/24 h]均明显下降(P<0.001),而Insulin组[(13.05±0.81)mmol/L]血糖明显下降(P<0.001),但对尿蛋白[(262±34.40)μg/24 h]作用不明显。天狼星红染色结果显示对照组肾组织结构完整,肾间质未见胶原纤维沉积;T1DN组肾组织结构破坏,间质胶原纤维沉积明显增多(P<0.001);联合组上述病变明显减轻(P<0.001),Insulin组减轻效果不明显。T1DN组肾组织中FN和SOCS2表达明显增加,E-cadherin表达明显减少(P<0.001);联合组E-cadherin表达明显增加,FN和SOCS2表达明显减少(P<0.001);Insulin组的效果不明显。Pearson相关性分析显示,T1DN小鼠肾组织中SOCS2的表达水平与肾组织胶原纤维沉积量和FN呈正相关,与E-cadherin呈负相关。结论:SOCS2在T1DN肾组织的EMT过程中发挥重要作用。Objective:To investigate the role of suppressor of cytokine signaling(SOCS)2 in renal tubular epithelial to mesenchymal transition(EMT)in type 1 diabetic nephropathy(T1DN).Methods:28 male C57/BL6 mice were randomly divided into control group(n=7)and T1D group(n=21).The T1D group received a single fasting intraperitoneal injection of 100 mg/kg streptozotocin(STZ).After 48 hours,the random blood glucose level was 16.7 mmol/L,which was diagnosed type 1 diabetes(T1D).After T1D mice model successfully established,21 T1D mice were randomly divided into 3 groups:T1DN group(n=7),benazepril and insulin combined as combined group(n=7),insulin alone as insulin group(n=7).After continuous administration for 8 weeks,serum,urine,and kidney tissue were collected for biochemical,pathological,and related protein and mRNA detection.Results:Compared with the control group[(3.81±0.24)mmol/L,(32±4.68)μg/24 h],the blood glucose and urinary protein in the T1DN group[(21.70±2.26)mmol/L,(286±42.41)μg/24 h]were significantly increased(P<0.001);blood glucose and urinary protein in the combination group[(11.84±0.69)mmol/L,(173±17.83)μg/24 h]were greatly decreased(P<0.001);while blood glucose in the Insulin group[(13.05±0.81)mmol/L]decreased significantly(P<0.001),but the effect on urinary protein[(262±34.40)μg/24 h]was not obvious.Sirius red staining showed that the kidneys in the control group were structurally intact and no collagen fibers deposited in the renal interstitium;renal tissue structure in the T1DN group was destroyed and interstitial collagen fibers deposition was significantly increased(P<0.001);the above-mentioned lesions in the combined group were significantly alleviated(P<0.001),while the effect was not obvious in the Insulin group.The expressions of FN and SOCS2 in the renal tissue of T1DN group were significantly increased,and the expression of E-cadherin was greatly decreased(P<0.001);the expression of E-cadherin in the combined group was significantly increased,and the expression of FN and SOCS2 was greatl

关 键 词：1型糖尿病肾病 上皮-间质细胞转分化 细胞因子信号传导抑制因子2 

分 类 号：R392.6[医药卫生—免疫学]