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目的:探讨血管生成素(angiopoietins,Ang)及其受体Tie-2和血管内皮生长因子(VEGF)在糖尿病大鼠肾组织中的表达以及罗格列酮对其表达的影响。方法:18只SD大鼠随机分为正常对照组(C组)、糖尿病组(D组)和糖尿病罗格列酮治疗组(R组)。实时定量RT-PCR和免疫组化方法分别检测3组大鼠肾组织中Ang-1、Ang-2、Tie-2和VEGF的表达;Western印迹法检测3组大鼠肾组织中Ang-2的蛋白表达。结果:实时定量RT-PCR和与Western印迹法结果显示,Ang-2糖尿病组[(80.88±28.30)&(0.76±0.19)]表达,较对照组[(47.81±20.50)&(0.28±0.07)]明显升高(P<0.05);经罗格列酮治疗后,Ang-2表达[(52.35±8.50)&(0.45±0.04)]显著下调(P<0.05)。相关分析显示,Ang-2mRNA水平与尿蛋白/肌酐值(Upro/Ucr)、平均肾小球体积(VG)和肾小球细胞外基质相对含量(RM)呈显著正相关(r=0.505,P=0.027;r=0.490,P=0.033;r=0.471,P=0.042)。结论:Ang-2的异常表达可能在早期糖尿病肾病的发病机制中起了重要的作用。罗格列酮可能通过下调糖尿病大鼠肾组织Ang-2的表达而发挥肾保护作用。
Objective: To investigate the expression of angiopoietins (Ang) and its receptors Tie-2 and vascular endothelial growth factor (VEGF) in the kidney of diabetic rats and the effect of rosiglitazone on their expression. Methods: Eighteen SD rats were randomly divided into normal control group (C group), diabetic group (D group) and diabetic rosiglitazone treatment group (R group). The expression of Ang-1, Ang-2, Tie-2 and VEGF were detected by real-time quantitative RT-PCR and immunohistochemistry in each group. Western blotting was used to detect Ang-2 Protein. Results: Compared with the control group [(47.81 ± 20.50) vs (0.28 ± 0.07)), the expression levels in Ang-2 diabetic group [(80.88 ± 28.30) vs (0.76 ± 0.19) ] (P <0.05). After rosiglitazone treatment, the expression of Ang-2 was significantly decreased (52.35 ± 8.50 vs 0.45 ± 0.04) (P <0.05). Correlation analysis showed that there was a significant positive correlation between Ang-2mRNA and Upro / Ucr, mean glomerular volume (VG), and glomerular extracellular matrix (RM) (r = 0.505, P = 0.027; r = 0.490, P = 0.033; r = 0.471, P = 0.042). Conclusion: The abnormal expression of Ang-2 may play an important role in the pathogenesis of early diabetic nephropathy. Rosiglitazone may exert renal protective effect by down-regulating the expression of Ang-2 in the kidney of diabetic rats.