糖尿病肾损伤大鼠空腹血清脂肪细胞型脂肪酸结合蛋白、游离脂肪酸的动态观察及意义

Fasting serum FABP4,FFA in STZ-induced diabetic rat model renal damage in diabetes mellitus

目的动态观察链脲佐菌素(STZ)诱发1型糖尿病肾损伤大鼠空腹血清脂肪细胞型脂肪酸结合蛋白(FABP4)、游离脂肪酸(FFA)的含量和血糖、血脂、血肌酐、尿素氮、尿白蛋白等指标的变化,探讨FABP4及FFA与糖尿病肾损伤发病的关系。方法选择健康的无特定病原体(specific pathogen free,SPF)级雄性Wistar大鼠28只作为建模对象,随机分为两组:对照组n=8、糖尿病组(DM组)n=20。收集3天,1,2,4,8周24小时尿,用酶联免疫吸附实验(ELISA)法检测24小时尿白蛋白。1,2,4,8周取空腹末梢静脉血(眼内眦静脉),统一测定FABP4、FFA、血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)和其他血生化指标。结果与对照组相比,DM组血清FABP4及FFA水平第1周即升高,2、4、8周血清FABP4及FFA水平均高于对照组,差异有统计学意义(P<0.05);DM组FABP4、FFA每个时间点差异均无统计学意义(P>0.05);Spearman相关分析显示,空腹血清FABP4水平与FFA(r=0.512,P<0.01)、FBG(r=0.434,P<0.01)、TG(r=0.360,P<0.05)、24小时尿白蛋白(r=0.583,P<0.01)呈明显正相关,与血ALB(r=-0.485,P<0.01)呈负相关,与TC(r=0.13,P>0.05)无相关性,空腹血清FFA水平与FBG(r=0.490,P<0.01)、TG(r=0.542,P<0.01)、TC(r=0.370,P<0.01)、24小时尿白蛋白(r=0.634,P<0.01)呈明显正相关,与血ALB(r=-0.278,P<0.01)呈负相关。结论糖尿病肾损伤大鼠第1周即有空腹血清FABP4、FFA有意义增高,这种升高比空腹血糖的升高更敏感,代谢紊乱是糖尿病的早期事件,提示空腹血清FABP4、FFA测定可能作为糖尿病肾损伤早期诊断的指标。

Objective To dynamically observe the changes of fasting serum adipocyte fatty acid binding protein （FABP4）,free fatty acids （FFA）,fasting blood glucose（FBG）,serum lipid,creatinine（CRE）,blood urea nitrogen （BUN）and urinary albumin in streptozotocin（STZ）-induced renal damage of diabetic rats,and then to explore the relationship between FABP4,FFA and renal damage of diabetes mellitus.Methods 28 male SPF Wistar rats were randomly divided into two groups：control group （group C,n = 8 ）and STZ-induced renal damage of diabetic rats （group DM,n =20）.Urine of each rat in both groups was collected at 3 d,1,2,4 and 8 w after the modeling for the determination of 24 h urine albumin using ELISA.Fasting serum samples at 1,2,4 and 8 w after the modeling were obtained by separating the peripheral venous blood and stored at -20 ℃ for the detection of FABP4,FFA,FBG,lipid （TG,TC）and other biochemical indicators.Results The fasting serum levels of FABP4 and FFA in DM group increased gradually after the modeling and were significantly higher than those in the control group at 2,4 and 8 w after modeling （P 〈0.05,respectively）.However,there were no significant difference among the four time points （P 〉0.05）.The correlation analysis showed that fasting serum level of FABP4 was positively correlated with FFA （r =0.5 12,P 〈0.01）,FBG（r =0.434,P 〈0.01）,TG（r =0.360,P 〈0.05）and 24 h urine albumin （r =0.583,P 〈0.01）,but was negatively correlated with serum ALB （r = -0.485,P 〈 0.01 ）and uncorrelated with TC （P 〉0.05）.Similarly,the fasting serum level of FFA was positively correlated with FBG （r =0.490,P 〈0.01）,TG（r =0.542,P 〈0.01 ）,TC（r = 0.37,P 〈 0.01 ）and 24 h urine albumin （r = 0.634,P 〈 0.01 ）,but was negatively correlated with serum ALB （r =-0.278,P 〈0.01）.Conclusion The elevation of serum FABP4 and FFA may be the early event in renal damage of diabetes mellitus and probably associated with the pathogenesis of this disease.