Wang Shuai, Li Yi, Huang Yun-Jian
Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2011 Sep;27(9):1003-6.
To explore the effect of VEGF inhibitor SU5416 on podocytopathy of rats with type I diabetic nephropathy.
Thirty male SD rats were randomly divided into three groups: normal control group(NC), diabetic nephropathy group(DN) and diabetic nephropathy treated with SU5416 group(SU5416). Rats with DN were induced by STZ. At the end of 8 weeks after SU5416 treatment, body weight (BW), kidney weight (KW), 24 h urine albuminuria excretion rate(24 h UAER), plasma glucose and creatinine were detected respectively. Renal morphology were stained with periodic acid-Schiff (PAS). And the expression of podocyte-specific genes nephrin and podocin were detected by immunofluorescence. The mRNA levels of genes and VEGF were assessed by real time-PCR respectively.
Compared with NC group, DN rats'BW were decreased but the KW were increased, and the levels of blood glucose, creatinine, 24 h UAER and kidney cortex VEGF mRNA were significantly higher. The expression of nephrin and podocin were decreased(P<0.05), and GBM thickening and mesangial matrix expansion were developed. Treatment with SU5416 leads to a marked decrease of KW and the level of 24 h UAER. Concurrently, the expressions of nephrin and podocin were revert partly in response to SU5416(P<0.05), and pathological changes were successfully ameliorated. However, the KW, glucose, creatinine and the level of VEGF mRNA were not significantly affected by SU5416 treatment(P>0.05).
VEGF-R inhibitor SU5416 can obviously ameliorate albuminuria and histologic changes, and restore the expression of podocyte-specific genes nephrin and podocin in DN rats, suggesting that VEGF-R inhibitor is beneficial for the repair of podocytes in DN, which might be an important adjunct for podocytopathy therapy.
探讨血管内皮生长因子（VEGF）抑制剂SU5416对Ⅰ型糖尿病肾病大鼠足细胞病变的影响。
将30只雄性SD大鼠随机分为三组：正常对照组（NC）、糖尿病肾病组（DN）和SU5416治疗糖尿病肾病组（SU5416）。采用链脲佐菌素（STZ）诱导建立DN大鼠模型。SU5416治疗8周后，分别检测大鼠体重（BW）、肾重（KW）、24小时尿白蛋白排泄率（24 h UAER）、血糖及肌酐水平。采用高碘酸-希夫（PAS）染色观察肾脏形态。通过免疫荧光检测足细胞特异性基因nephrin和podocin的表达。分别采用实时荧光定量PCR检测相关基因及VEGF的mRNA水平。
与NC组相比，DN大鼠BW降低，KW增加，血糖、肌酐、24 h UAER及肾皮质VEGF mRNA水平显著升高。nephrin和podocin表达降低（P<0.05），肾小球基底膜（GBM）增厚，系膜基质扩张。SU5416治疗后KW及24 h UAER水平显著降低。同时，nephrin和podocin的表达部分恢复（P<0.05），病理改变得到改善。然而，SU5416治疗对KW、血糖、肌酐及VEGF mRNA水平无显著影响（P>0.05）。
VEGF受体抑制剂SU5416可明显改善DN大鼠蛋白尿及组织学改变，恢复足细胞特异性基因nephrin和podocin的表达，提示VEGF受体抑制剂对DN足细胞修复有益，可能是足细胞病变治疗的重要辅助药物。
