CAJ | 학술논문

目的:探讨在2型糖尿病大鼠心肌损伤时肿瘤坏死因子(TNF)-α、核转录因子(NF)-κB介导的炎症反应中小泛素相关修饰蛋白1 (SUMO 1)可能的作用.方法:20只自发性糖尿病(GK)大鼠被随机分为DM1组(单纯糖尿病组,n=10)、DM2组(糖尿病+高脂饮食组,n=10),另10只Wistar大鼠为健康对照组,以免疫组织化学法检测SUMO1、TNF-α和NF- κB的表达.结果:1、DM1、DM2组血糖及TG水平明显高于健康对照组,DM2的又显著高于DM1组的(P均＜0.05)；2、光镜下:DM1组心肌细胞排列整齐,无明显肥大；DM2组心肌细胞肥大呈疏松样排列；3、免疫组化显示:SUMO 1表达在DM2组和DM1组较健康对照组明显增加[(44.5±1.1)比(27.2±2.2)比(21.7±3.0)],且DM2组的较DM1组的显著增加(P均＜0.01)；TNF-α表达在DM2组和DM1组较健康对照组明显增加[(27.5±1.5)比(20.2±2.7)比(13.1±1.6)],且DM2组的较DM1的显著增加(P均＜0.01)；NF-κB表达在DM2组和DM1组较健康对照组明显增加[(30.1±1.7)比(40.7±1.5)比(16.0±2.6)],但DM1组的较DM2组的显著增加(P均＜0.01).结论:2型糖尿病大鼠存在着明显的糖脂代谢紊乱,伴有与人类糖尿病心肌病变相似的心肌组织形态学改变；且血SUMO1、TNF-α和NF-κB的表达均显著增加,提示SUMO1参与了2型糖尿病大鼠心肌病变由NF- κB、TNF-α介导的炎症反应,并有抑制NF-κB,保护心肌的作用.
목적:탐토재2형당뇨병대서심기손상시종류배사인자(TNF)-α、핵전록인자(NF)-κB개도적염증반응중소범소상관수식단백1 (SUMO 1)가능적작용.방법:20지자발성당뇨병(GK)대서피수궤분위DM1조(단순당뇨병조,n=10)、DM2조(당뇨병+고지음식조,n=10),령10지Wistar대서위건강대조조,이면역조직화학법검측SUMO1、TNF-α화NF- κB적표체.결과:1、DM1、DM2조혈당급TG수평명현고우건강대조조,DM2적우현저고우DM1조적(P균＜0.05)；2、광경하:DM1조심기세포배렬정제,무명현비대；DM2조심기세포비대정소송양배렬；3、면역조화현시:SUMO 1표체재DM2조화DM1조교건강대조조명현증가[(44.5±1.1)비(27.2±2.2)비(21.7±3.0)],차DM2조적교DM1조적현저증가(P균＜0.01)；TNF-α표체재DM2조화DM1조교건강대조조명현증가[(27.5±1.5)비(20.2±2.7)비(13.1±1.6)],차DM2조적교DM1적현저증가(P균＜0.01)；NF-κB표체재DM2조화DM1조교건강대조조명현증가[(30.1±1.7)비(40.7±1.5)비(16.0±2.6)],단DM1조적교DM2조적현저증가(P균＜0.01).결론:2형당뇨병대서존재착명현적당지대사문란,반유여인류당뇨병심기병변상사적심기조직형태학개변；차혈SUMO1、TNF-α화NF-κB적표체균현저증가,제시SUMO1삼여료2형당뇨병대서심기병변유NF- κB、TNF-α개도적염증반응,병유억제NF-κB,보호심기적작용.
Objective:To study effect of small ubiquitin related modifier protein 1 (SUMO1) in inflammatory reactions mediated by tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB in myocardial damage of rats with type 2diabetes mellitus (T2DM).Methods:A total of 20 Goto-Kakizaki (GK) rats with spontaneous diabetes mellitus (DM) were randomly divided into group DM1 (pure DM group,n=10) and group DM2 (DM+high-fat diet group,n=10),and another 10 normal Wistar rats wereregard as healthy control group.Expressions of SUMO1,TNF-αand NF-κB were measured by immunohistochemical method.Results:1.Levels of blood glucose and TG in group DM1 and group DM2 were significantly higher than those of healthy control group,and those of group DM2 were higher than those of group DM1,P＜0.05 all; 2.Myocardial cells lined up in order and there was no hypertrophy in group DM1; but those in group DM2 showed cells loosely lined up and hypertrophy under light microscope; 3 Immunohistochemical assay indicated that expression of SUMO1 in group DM2 and group DM1 were significantly higher than those of healthy control group [(44.5±1.1) vs.(27.2±2.2) vs.(21.7±3.0)],and of group DM2 was significantly higher than that of group DM1(P＜0.01 all) ; expression of TNF-α in group DM2 and group DM1 were significantly higher than that of healthy control group [(27.5±1.5) vs.(20.2±2.7) vs.(13.1± 1.6)],and of group DM2 was significantly higher than that of group DM1 (P＜0.01 all) ;expression of NF-κB in group DM2 and group DM1 were significantly higher than that of healthy control group [ (30.1 ± 1.7) vs.(40.7 ± 1.5) vs.(16.0 ± 2.6) ],but of group DM1 was significantly higher than that of group DM2 (P＜0.01 all).Conclusion:There are obvious metabolic disorders of glucose and lipid in T2DM rats,and complicated morphological changes of myocardial tissues similar to myocardial lesions in DM humans; the expressions of SUMO1,NF-κB and TNF-α significantly increase,suggest SUMO1 takes part in inflammatory reaction mediated by NF-κB,TNF-α in myocardial lesion of rat with T2DM,and may inhibit NF-κB,possesses effect of protect myocardium.