螺内酯对单肾切除糖尿病大鼠肾脏保护作用研究

目的：研究螺内酯对单肾切除糖尿病SD大鼠的肾脏保护作用及机制。方法：48只雄性SD大鼠随机分为单肾切除对照组C组、单肾切除糖尿病模型组D组、单肾切除糖尿病螺内酯干预组S组（50mg/kg/day灌胃）。给药6周后观察各组大鼠生化指标改变,肾组织形态学改变,RT-PCR及Western Blot检测肾组织中HGF水平的变化。结果：给药6周后,D组与C组相比,血糖、24h尿蛋白定量、尿素氮、血肌酐和肾重/体重显著增高（P〈0.05）,螺内酯治疗后可降低糖尿病大鼠的24h尿蛋白定量和肾重/体重,但对其它指标无明显影响;形态学显示,D组与C组相比肾小球系膜区细胞外基质增多及系膜细胞增生,肾小球基底膜增厚,足细胞足突融合、消失;螺内酯治疗后上述病理改变均有不同程度的减轻;RT-PCT、Western Blot结果显示D组和S组HGF表达均增加（P〈0.05）,而D组HGF表达明显低于螺内酯治疗组。结论：螺内酯可能通过上调HGF的水平从而起到保护糖尿病大鼠肾脏作用。

Protection of Spironolactone on the Kidney in Diabetic Rats Undergoing Mono-nephrectomy

Objective：To investigate the effect of spironolactone on the mono-nephrectomy diabetic SD rats and to explore the possible mechanism.Methods：48 male SD rats were randomly divided into three groups：mono-nephrectomy control rats（group C）,mono-nephrectomy diabetic rats（group D）,and mono-nephrectomy diabetic rats treated with spironolactone（group S,50mg/kg/day,intragastric administration）.6 weeks after treatment,biochemical indicators and renal tissue morphology were detected.The mRNA and protein expression levels of HGF were detected by RT-PCR and Western Blot respectively.Results：Blood sugar,24 hours urinary protein,serum creatinine（SCr）,urea nitrogen（BUN）,and ratio of renal weight/ body weight increased in mono-nephrectomy diabetic rats（group D） compared with those in the mono-nephrectomy control rats（group C）（P0.05）.Spironolactone could decrease the 24 hours urinary protein and ratio of renal weight/ body weight,but had no obvious effect on the other indicators in diabetic rats.Compared with group C,there was the expansion of extracellular matrix with proliferated intercapillary cells in the expanded mesangial area,the thickening of basement membrane（GBM） in group D.Foot processes even fused or disappeared in the rats of group D.Meanwhile,the renal pathologic changes as above were improved in the rats of group S..The mRNA and expression of HGF were up-regulated in the rats of group D and S,especially in the group S（P0.05）.Conclusion：Spironolactone ameliorates the glomerular injury in diabetic rats presumably via up-regulation of HGF expression level.