SUMO4、NF-κB、IκB在2型糖尿病大鼠肾脏中的表达及意义

摘要

Objective:To study expressions of small ubiquitin-related modifier protein (SUMO) 4 (SUMO4),nuclear factor (NF) -κB and inhibitory factor of NF-κB (IκB) in kidneys of rats with type 2 diabetes mellitus (T2DM).Methods:A total of ten 40-week-old male Goto-Kakizaki (GK) rats (with spontaneous diabetes mellitus) of specificpathogen free (SPF) grade,and ten 40-week-old male Wistar rats of SPF grade were selected.The lesion of renal tissue was observed by hematoxylin eosin (HE) staining.Experssions of SUMO4,NF-κB and IκB in renal tissue were observed by immunohistochemistry methods.Results:In the GK rats,glomerular capillary ball hypertrophy,basilar membrane slightly thickening; glomerular mesangial cells hyperplasia,hypertrophy and renal tubular epithelial cells hypertrophy were observed.Compared with normal Wistar rats,expression levels of NF-κB [ (0.232 ±0.034) vs.(0.634± 0.058)],IκB [ (0.242 ± 0.027) vs.(0.712 ± 0.078)] and SUMO4 [ (0.160 ± 0.031) vs.(0.545 ± 0.045)] significantly increased in renal tissue of GK rats (P＜0.01 all).Conclusion:Compared with Wistar rats,expressions of NF-κB,IκB and SUMO4 significantly increase in renal tissue of GK rats,suggesting that SUMO inhibiting transcriptional activity of NF-κB may exist in kidneys of T2DM rats.Therefore,sumoylation may be a new therapeutic target for inhibit renal microvascular lesion of diabetic disease.%目的:探讨2型糖尿病大鼠肾脏组织小泛素相关修饰蛋白4 (SUMO4)、核转录因子(NF) -κB、NF-κB的抑制因子(IκB)的表达及意义.方法:取10只40周龄的无特定病原体(SPF)级雄性自发性糖尿病(GK)大鼠,10只40周龄的SPF级雄性Wistar大鼠,通过HE染色法观察肾组织病变、免疫组化法观察肾组织的SUMO4与IκB、SUMO4与NF-κB表达情况.结果:GK大鼠的肾小球毛细血管球肥大,基底膜轻度增厚,肾小球系膜细胞增生、肥大,肾小管上皮细胞肥大.与正常Wistar大鼠比较,GK大鼠的肾脏NF-κB[ (0.232±0.034)比(0.634±0.058)]、IκB[(0.242±0.027)比(0.712±0.078)]及SUMO4[(0.160±0.031)比(0.545±0.045)]的表达水平均明显升高(P均＜0.01).结论:NF-κB、IκB及SUMO4在GK大鼠肾脏组织表达增多.从而推断在2型糖尿病大鼠肾脏SUMO可能抑制NF-κB转录活性,SUMO化可能成为治疗糖尿病肾脏微血管病变的一个新靶点.