维格列汀对糖尿病肾病保护作用机制探讨

摘要

目的：研究结缔组织生长因子（CTGF）和血管内皮生长因子（VEGF）在大鼠糖尿病肾病发生和发展中的作用，探讨维格列汀对糖尿病肾病的保护机制。方法将60只大鼠分为A、B、C 3组，A、B两组给予链脲佐菌素用于制备大鼠糖尿病肾病模型组，然后分别给予维格列汀8 mg／（kg · d）灌胃连续治疗8周和12周，C组为对照组，只给予生理盐水灌胃。处死大鼠，检测A、B两组大鼠血糖、24 h尿蛋白定量和血清CTGF和VEGF表达水平。进一步测定肾重指数，形态学观察肾小球体积及肾小球基底膜变化，测定肾小球平均截面积（MGA），计算肾小球平均体积（MGV），比较其MGA和MGV。结果大鼠糖尿病组血糖、24 h尿蛋白定量和CTGF、VEGF水平明显高于对照组。经维格列汀治疗后大鼠糖尿病肾病组血糖、24 h尿蛋白定量和CTGF、VEGF水平显著下降，治疗12周后以上各项指标比治疗8周下降更明显，肾重指数降低，肾脏肥大程度减轻，且治疗前、后CTGF和VEGF水平呈正相关。结论 CTGF和VEGF可作为糖尿病肾病患者病情评估有价值的指标，维格列汀可能部分通过调控CT‐GF和VEGF的表达而发挥肾脏保护作用。%Objective To study the role of CTGF and VEGF in the occurrence and development of rat diabetic nephropathy ,and to investigate the protection mechanism of vildagliptin to diabetic nephropathy .Methods 60 rats were divided into three groups :group A ,B and C .Group A and B were treated by streptozotocin for the preparation of diabetic nephropathy rat models .Then the diabetic nephropathy rats of group A and B were treated by continuous intragastric administration of 8 mg/(kg · d) vildagliptin for 8 and 12 weeks respectively .Group C was control group , and just given intragastric administration of saline .The rats were killed ,then blood glucose ,24 h urine protein ,and the expression levels of CTGF and VEGF of rats in group A and B were detected .Furthermore ,kidney weight index , morphological observation of glomerular volume ,glomerular basement membrane changes were determinated as well as the glomerular average sectional area (MGA) and the average calculated glomerular volume (MGV) were com‐pared .Results The levels of blood glucose ,24 h urine protein ,CTGF and VEGF of group A and B were significantly higher than those of control group .After vildagliptin treatment ,the levels of blood glucose ,24 h urine protein ,CTGF and VEGF reduced in both of group A and B ,and those in group B reduced more significantly than group A .At the same time ,both of the kidney weight index and the degree of renal hypertrophy reduced after treatment ,and the lev‐els of CTGF and VEGF were positively correlated before and after treatment .Conclusion CTGF and VEGF could serve as a valuable indexes of diabetic nephropathy .Vildagliptin might play a role of renal protection via partially reg‐ulate the expression of CTGF and VEGF .