EGCG对实验性糖尿病大鼠肾脏的保护作用

目的观察表没食子儿茶素没食子酸酯(EGCG)对大鼠糖尿病肾脏的保护作用。方法采用链脲佐菌素(65 mg.kg-1)腹腔注射建立糖尿病大鼠模型,实验分4组:对照组、模型组、EGCG治疗组Ⅰ和治疗组Ⅱ,后两组于模型成功后1 wk和4 wk给予EGCG 5 mg.kg-1.d-1腹腔注射。分别测定各组4、8、12 wk时尿白蛋白/肌酐比值(A/C)。12 wk后,采用高效液相测定血浆同型半胱氨酸(tHcy)含量;观察肾脏损伤后病理形态学变化;应用免疫组化检测肾组织细胞外基质蛋白酶-9(MMP-9)的表达;生化分析肾脏氧化应激状态。结果模型组与对照组相比:大鼠肾重/体重明显升高;肾小球肥大,细胞增生,PAS阳性物质明显沉积;血浆tHcy含量及肾组织MMP-9的表达明显增加。经EGCG干预后大鼠生化指标和肾重/体重明显改善;肾脏的抗氧化能力增强和氧化应激降低;血浆tHcy含量下降和MMP-9的表达减弱。EGCG两治疗组相比较,其结果也存在差异。模型组大鼠尿A/C在不同时相点都维持在高水平,且随着时间的延长而逐渐升高,EGCG治疗组I在各时间点与模型组相比A/C明显降低(P<0.01),而治疗组Ⅱ在12 wk时明显低于模型组(P<0.05),在不同时间点治疗组I和治疗组Ⅱ之间存在差异。结论EGCG对糖尿病肾病具有保护作用,其作用机制可能是通过提高机体抗氧化应激能力,降低血浆tHcy含量,抑制肾组织MMP-9表达而减少糖尿病肾病损害。

Protective effect of EGCG on experimental diabetic nephropathy in rats

Aim To observe the protective effect of EGCG(epigallocatechin-3-gallate) on experimental diabetic nephropathy in rats.Methods SD rats were randomly divided into four groups: control group,model group,EGCG-treatment I group and EGCG-treatment II group.First,the latter three groups were induced to be diabetic nephropathy by intraperitoneal injection with 65 mg·kg~(-1) streptozoticin,and then,5 mg·kg~(-1)·d~(-1) EGCG was continuously given 1 wk after STZ injection in EGCG-treatment I group,and 4 wk after STZ injection in EGCG-treatment Ⅱ group.Urine albumen/creatinine value(A/C) was observed in the rats at week 4,8 and 12 respectively.Profile of kidney hypertrophy (KW/BW),mean glomerular area(MGA) and mean glomerular volume(MGV) were determined at week 12.Renal expression of MMP-9 were detected by immunohistochemical method and the plasm tHcy concentration was detected by high performance liquid chromatography(HPLC).Results After 12 weeks,the plasm Hcy concentration,urine A/C and the expression of MMP-9 increased in renal tissue of diabetic rats,compared with those of control group.EGCG markedly decreased the level of A/C,the plasm Hcy conceration and the expression of MMP-9 in renal tissue of diabetic rats(P<0.05).In addition,A/C was significantly reduced in EGCG-treatment I group from 4 to 12 wk,compared with that of model groups.However,A/C was significantly decreased in EGCG-treatment Ⅱ group from 12 wk.Conclusion EGCG can reduce the diabetic nephropathy impairment through inhibiting the plasm Hcy and the expression of renal MMP-9.