氟伐他汀对糖尿病肾病鼠血管内皮生长因子表达的影响

Effects of Fhvastatin on the Expression of Vascular Endothelial Growth Factor of Diabetic Nephropathy in Rats

目的:探讨氟伐他汀对糖尿病肾病(DN)大鼠肾组织血管内皮生长因子(VEGF)mRNA及蛋白质表达的影响。方法:SD大鼠分为对照组、DN组、氟伐他汀治疗组,链脲菌素腹腔注射诱导DN大鼠模型,诱导成功后氟伐他汀治疗组给予氟伐他汀经胃管灌服。试验12周末检测大鼠体重、血糖、尿肌酐、24 h尿白蛋白。采用RT-PCR检测VEGF mRNA及免疫组化检测蛋白质的表达。结果:DN组大鼠体重、血糖、尿白蛋白,VEGF mRNA及蛋白质的表达,肾小球细胞数,细胞外基质(ECM)聚积均高于对照组(P<0.01)。与DN组相比,氟伐他汀治疗组大鼠体重、血糖、尿白蛋白,肾脏VEGF mRNA及免疫组化检测蛋白质的表达,ECM聚积显著降低(P<0.01或P<0.05)。尿VEGF与尿白蛋白呈正相关(r=0.42,P=0.039),与尿肌酐亦呈正相关(r=0.35,P=0.043)结论:VEGF表达增加可能参与DN的发病机制。氟伐他汀可减轻DN大鼠体重、血糖,减少尿白蛋白的排泄,抑制肾小球系膜增殖及硬化,降低VEGFmRNA及蛋白质的表达。

Objective： To investigate the effects of fluvastatin on the expression of renal vascular endothelial growth factor（VEGF） mRNA and protein of diabetic nephropathy （DN） in rats. Method： SD rats were divided into control group, diabetic nephropathy group （DN group）, fluvastatin treated group. DN was induced by peritoneal injection of streptozotocin（ STZ）, with or without treatment by gastric perfusion of fluvastatin daily until 12 weeks after the experiment. The body weights, blood glouse, urine creatinine ,24 hour total urinary albumin were measured. The expression of VEGF mRNA was determined by reverse transeription-polymerase chain reaction （RT-PCR） and the protein was detected by immunohistoehemieal staining. Result： The body weight, blood glucose, urinary albumin, expression of VEGF mRNA and protein, glomerular cellularity and extraeellular matrix（ECM） increased significantly in nephritic rats without treatment with fluvastatin as compared to those in control rats （P 〈 0.01 ）. However, the body weight, blood glucose, urinary albumin, expression of VEGF mRNA and protein, ECM decreased significantly in fluvastatin-treated nephritic rats as compared to those in nephritic rats without treatment with fluvastatin（ P 〈 0.01 or P 〈 0.05 ）. The positive correlations were found between urinary levels of VEGF and urinary albumin（ r = 0.42, P = 0. 039） , and between urinary levels of VEGF and urine ereatinine （r = 0. 35, P = 0.043 ）. Conclusion： The overexpression of VEGF may participate in the pathogenesis of diabetic nephropathy. Fluvastatin could contribute to decrease body weights, blood glouse ,urinary albumin exereetion,inhibit glomerular cellularity and ECM proliferation, downregulate the expression of VEGF mRNA and protein.