摘要
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。
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.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2006年第1期84-88,共5页
Chinese Pharmacological Bulletin
基金
教育部归国人员启动基金资助项目
