舒洛地特对SUMO4介导的2型糖尿病大鼠肾脏的保护作用

目的：探讨舒洛地特对小泛素养修饰蛋白（SUMO）4介导的2型糖尿病大鼠肾脏功能的保护作用.方法：将20只GK大鼠按数字表法随机均分为糖尿病组（DM组）、舒洛地特治疗组（DM＋S组）,SPF级同龄雄性Wistar大鼠10只作为健康对照组,DM＋S组给予舒洛地特10mg· kg-1·d-1腹腔注射,连续8周,其余两组给予等体积生理盐水注射.分别于用药前1d和用药结束后次日测定24 h尿微量白蛋白量,光镜下观察肾脏组织的结构变化,免疫组化法检测三组大鼠肾脏组织中核转录因子-κB（NF-κB）、SUMO4、NF-κB抑制剂（IκB）的表达.结果：（1）用药前DM组与DM＋S组大鼠的血糖及24 h尿白蛋白排泄率显著高于健康对照组（P＜0.01）；用药后DM＋S组24 h尿白蛋白排泄率显著低于DM组（146.90±10.92）％比（314.63±20.42）％,P＜0.01]；（2）与健康对照组相比,光镜下GK大鼠的肾脏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.未见典型的结节性肾小球硬化,似为糖尿病肾损害的早期改变,DM＋S组肾脏组织病理改变较DM组明显减轻；（3）免疫组化示：DM＋S组和DM组SUMO4、NF-κB、IκB表达显著高于健康对照组；与DM组比较,DM＋S组SUMO4（29.8±0.6）比（34.2±0.7）]、IκB（25.5±0.7）比（37.3±0.6）]表达显著增加,NF-κB（43.9±0.9）比（27.0±0.6）]表达显著减少,P均＜0.05.结论：（1）小泛素养修饰蛋白4、NF-κB抑制剂在糖尿病GK大鼠肾脏组织表达增多；（2）舒洛地特对糖尿病GK大鼠肾脏组织有一定的保护作用.

Protection effect of sulodexide on kidney of rats with type 2 diabetes mellitus mediated by SUMO4

Objective：To explore protection effect of sulodexide on renal function of rats with type 2 diabetes mellitus （T2DM） mediated by small ubiquitin related modifier protein （SUMO） 4.Methods：A total of 20 GK rats were randomly and equally divided into DM group and sulodexide treatment group （DM ＋ S group） according to number table.Another 10 male Wistar rats of same age and SPF level were enrolled as healthy control group.DM ＋ S group received intraperitoneal injection of sulodexide 10mg · kg-1 · d-1 for continuous eight weeks,the other two groups received normal saline injection of the same volume.The 24h urinary microalbumin was measured 1d before and after medication.Light microscope was used to observe structural change of renal tissues,immunohistochemical method was used to measure expressions of nuclear factor-κB （NF-κB）,SUMO4 and inhibitor of NF-κB （IκB） in renal tissue of three groups of rats.Results：（1） Compared with healthy control group before treatment,there were significant increase in blood glucose and 24h urinary albumin excretion rate （UAER） in DM group and DM ＋ S group （P〈0.01） ; compared with DM group after treatment,there was significant decrease in 24h UAER （314.63 ± 20.42）% vs.（146.90± 10.92）%,P〈0.01] in DM ＋ S group; （2） Compared with healthy control group,there were glomerular capillary ball hypertrophy,mild thickening of basilar membrane,hyperplasia and hypertrophy of mesangial cells and renal tubular epithelial cell hypertrophy in kidney of GK rats under light microscope.There was no typical nodular glomerulosclerosis and was early change looked like renal damage of DM.Pathological change of renal tissue in DM ＋ S group was significantly relieved compared with that of DM group; 3.Immunohistochemistry indicated that compared with healthy control group,there were significant increase in expressions of SUMO4,NF-κB and IκB in DM ＋ S group and DM group; compared with DM group,there were significant increase in expressions of SUMO4（29.8±0.6） vs.（34.2±0.7）] and IκB（25.5±0.7） vs.（37.3±0.6）],and significant decrease in N F-κB expression （43.9 ± 0.9） vs.（27.0 ± 0.6）] in D M ＋ S group,P〈0.05 all.Conclusion：（1） There are significant increase in expressions of small ubiquitin related modifier protein 4 and inhibitor of NF-κB in renal tissue of GK rats; （2） Sulodexide possesses certain protective effect on renal tissue of GK rats.