培哚普利对糖尿病肾病肾组织清道夫受体A基因表达的影响

Effect of perindopril on the expression of scavenger receptor A gene in diabetic nephropathy

目的 研究清道夫受体A（scavenger receptor A,SR-A）基因在糖尿病大鼠肾组织中的表达及血管紧张素转换酶抑制剂-培哚普利的干预作用.方法 将大鼠随机分为正常对照组,糖尿病组和ACEI干预组,采用一次性腹腔注射链脲佐菌素（STZ,60 mg/kg）的方法 建立糖尿病模型,ACEI干预组以培哚普利4mg/（kg·d）灌胃24周.检测各组大鼠的血糖和24 h尿白蛋白,行HE及Masson染色观察肾脏形态学变化,免疫组织化学检测肾小球和小管间质中CD68阳性的巨噬细胞,荧光实时定量PCR测定肾组织中SR-A mRNA表达水平.结果 与对照组相比,糖尿病组大鼠血糖和24 h尿白蛋白均显著上升[（5.3±0.6）mmol/L vs（26.7±3.3）mmol/L;（2.7±1.3）mg/24 h vs（26.7±1.8）mg/24 h;P＜0.05];细胞外基质增多,部分肾小管上皮细胞萎缩、空泡样变性;肾小球和小管间质CD68阳性的巨噬细胞数及肾组织SR-A mRNA的表达均显著上调[（0.77±0.24）个gcsvs（2.55±0.46）个/gcs;（6.13±0.50）个/HPF vs（11.9±2.12）个/HPF,5.6±1.2 vs 1.5±0.2,P＜0.05].ACEI干预后,上述指标除血糖外均被明显抑制[[（3.6±1.4）mg/24h;（1.03±0.37）/gcs;（8.28±1.19）/HPF;3.4±0.7,P＜0.05].结论 ACEI对糖尿病大鼠肾脏有保护作用,其机制可能部分与下调肾组织SR-A表达有关.

Objective To explore the effect of ACE-inhibitor perindopril on the expression of scavenger receptor A （SR-A） gene in the kidney of diabetic rats.Methods Diabetes were induced in male Sprague-Dawley rats by peritoneal injection with streptozotocin （60mg/kg）.The rats were then random di vided into normal control group, diabetes group and ACEI treatment group [4mg/（kg·d） for 24 weeks].Blood glucose concentration and 24h urinary albumin excretion were determined.The renal morphological change was observed.Immunohistochemistry was used to analyze CD68 positive macrophages,and the Mrna of SR-A in renal tissue was detected by quantitative real-time PCR.Results Compared with normal control group,blood glucose concentration,24h urinary albumin excretion and the number of CD68 positive macrophages were significantly increased [（5.3 ± 0.6） mmol/L vs （26.7 ± 3.3） mmol/L;（2.7 ± 1.3） mg/24h vs （26.7 ± 1.8）mg/24h;（0.77 ±0.24）/gcs vs （2.55 ±0.46）/gcs;（6.13 ±0.50）/HPF vs （11.9 ±2.12）/HPF;P 〈0.05],and the expression of SR-A Mrna were significantly up-regulated in diabetes group [ （5.6 ± 1.2 vs 1.5 ±0.2）,P 〈0.05].After intervention with ACE-inhibitor,the up-regulations of the above mentioned parameters,except blood glucose concentration,were all significantly inhibited [ （3.6 ±1.4）mg/24h;（1.03±0.37）/gcs;（8.28±1.19）/HPF;3.4±0.7;P 〈0.05].Conclusion ACE-inhibitor might have renoprotective effects of diabetic nephropathy,it probably was associated with inhibiting the expression of SR-A gene.