VEGF、bFGF和TGF-β_1在大鼠马兜铃酸肾损伤中的表达

目的观察3种致纤维化细胞因子:血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和转化生长因子-β1(TGF-β1)在大鼠马兜铃酸肾病肾损伤过程中的表达。方法实验组:Wistar大鼠20只,马兜铃酸Ⅰ(AAⅠ)50 mg.kg-1.d-1灌胃,连续7 d,分别于停药后第1、2、3、4周宰杀。对照组大鼠6只,纯净水灌胃,连续7 d,分别于第2和4周宰杀。免疫组织化学二步法观察各组大鼠肾脏VEGF、bFGF和TGF-β1的表达及产生规律。结果实验组于第2周起,出现明显的肾小管上皮细胞损害,初期以近曲肾小管病变为主,至第4周时病变累及各段肾小管,损害更为明显。VEGF、bFGF和TGF-β1的表达具有共同特点,阳性表达范围均随实验时间的延长呈逐渐扩大趋势,弥漫分布于肾皮髓质各段损伤的肾小管上皮细胞。各实验组与正常对照组VEGF、bFGF和TGF-β1的平均表达率比较差异均有统计学意义(P均<0.01)。结论马兜铃酸可以刺激致纤维化细胞因子VEGF、bFGF和TGF-β在肾小管上皮细胞内表达。VEGF、bFGF、TGF-β的早期、过度表达可加重马兜铃酸肾病的进展。

Expression of VEGF, bFGF and TGF-β1 in Nephropathy Induced by Aristolochic Acid I in Rats

Objective To observe the expression of VEGF,bFGF and TGF-β₁ in nephropathy induced by aristolochic acid I in rats.Methods 20 female Wistar rats were in the experiment group and their stomachs were perfused with 50 mg·kg^-1·d^-1(AAⅠ) one time per day for 7 d continuously,and 6 rats were in the control group whose stomachs were perfused with pure water per day for 7 d,too.In the test group,every week 5 rats were killed from the first to the fourth week respectively,and in the control group,3 rats were killed in the second and fourth week respectively.The expression and regulation of VEGF,bFGF and TGF-β₁ in kidney in all groups were examined with 2-step immunohistochemistry.Results Since the second week,the transparent renal tubular epithelial defect were found in each test group;in the initial stage,the lesion mainly situated in the proximal convoluted tubule,in the fourth week,the lesion involved all of the renal tubules. From the first to the fourth week,the positive expression of VEGF,bFGF and TGF-β₁ in the test groups showed a tendency to expand gradually,and which were wide spreadly distributing over every segment of the renal tubular epithelial cells in the cortex and medulla.The quantity and degree of positive cells increased strikingly,and there was significant difference between the control and the test groups in the mean expression quantity(P<0.01).Conclusion AAⅠ can injure the renal tubular epithelial cell directly and induce the expression of VEGF,bFGF and TGF-β₁.The early and super expression of VEGF,bFGF and TGF-β₁ in the renal tubular epithelial cells may be the important cause of renal tubular interstitial lesion and interstitial fibrosis.