腺嘌呤所致大鼠慢性肾功能衰竭肾组织中TGF-β1、TSP-1、VEGF的表达

王国强; 陈卫东

腺嘌呤所致大鼠慢性肾功能衰竭肾组织中TGF-β1、TSP-1、VEGF的表达

The expressions of transforming growth factor-β1,thrombospondin-l and vascular endothelial growth factor in rat renal tissue in adenine-induced chronic renal failure

摘要

摘要: 目的:探讨腺嘌呤所致大鼠慢性肾功能衰竭(chronic renal failure,CRF)肾组织中转化生长因子-β1(transforning growth-β1,TGF-β1)、血小板反应因子-1(thrombospondin-1,TSP-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达情况。方法:雄性SD大鼠60只,随机分为两组:模型组(n=30),以2.5%腺嘌呤悬混液灌胃;正常对照组(n=30),给相同体积淀粉溶液灌胃。两组分别于7天、14天、21天留尿标本后,各处死大鼠10只,取血、肾脏标本。测定体重(BW)、24 h尿蛋白定量(24 h U-TP)、尿N-乙酰-β-D-氨基葡萄糖酐酶(NAG)、肾重指数(肾脏重量/体重,KI)、血肌酐(SCr)、血尿素氮(BUN)、血白蛋白(ALB),光镜下观察肾组织的病理变化,免疫组织化学法检测肾脏、TGF-β1、TSP-1、VEGF的表达情况。结果:7天时模型组大鼠与同时相点对照组相比,BW增加缓慢(P<0.01),ALB无明显变化;14天和21天时模型组大鼠与同时相点对照组和前一时相点自身对照比较,BW明显下降(P<0.01),血ALB明显降低(P<0.01);7天、14天和21天时模型组大鼠24 h U-TP、KI、尿NAG、SCr、BUN呈进行性升高(P<0.01)。7天、14天和21天时模型组大鼠TGF-β1和TSP-1表达均呈进行性增高(P<0.01)。在对照组肾组织中,VEGF广泛表达于肾小管上皮细胞及足突细胞,随着肾间质病理损害程度加重,模型组肾组织中VEGF的表达逐渐减少。在模型组大鼠各时相点中,肾间质TGF-β1表达量与肾小管TGF-β1表达量呈显著正相关(r_s=0.940,P<0.01);肾小管VEGF与TGF-β1表达量呈显著负相关(r_s=-0.945,P<0.01),同时与肾间质TSP-1呈显著负相关(r_s=-0.923,P<0.01)。各时相点对照组各指标无明显改变。结论:TSP-1-TGF-β1轴表达增强促使肾间质纤维化发生、发展,推测TSP-1在腺嘌呤灌胃法制备CRF模型中可能具有重要作用;VEGF表达下降也是导致肾间质纤维化发生、发展因素。

Abstract: Objective:To study the expressions of transforming growth factor-β1 (TGF-β1),thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF) in rat renal tissue in adenine induced chronic renal failure (CRF).Methods:Sixty male SD rats were randomly divided into two groups:model group (n=30),2.5% Adenine solution was administered by gastric garage daily;control group (n=30),the same volume torch solution was administered by gastric garage daily.At the 7th,14th and 21th day,ten rats in every group were sacrificed.Urine sample,blood sample and kidney tissue were reserved.The body weight (BW),kidney weight/body weight index (KI),the levels of 24 hours urine protein (24 h U-TP),N-acety1-β-D-glucosaminidase (NAG) in urine sample,blood urea nitrogen (BUN),serum creatinine (SCr) and blood albumin (ALB) in blood sample were examined.The histological changes of kidney were observed by light microscopy,and the expressions of TGF-β1,TSP-1,VEGF were examined by immunohistochemistrical method.Results:At the 7th day,rat BW in model group was increased slowly than that in control group (P<0.01);ALB was no significant change in these two groups.At the 14th and 21th day,BW and ALB in model group were decreased clearly than those in the same group at 7th day (P<0.01);At 7th,14th and 21th day,the levels of 24 h U-TP,NAG,BUN and SCr in model group were progressively increased (P<0.01).And the expressions of TGF-β1 and TSP-1 were also progressively increased.In control group,VEGF was broadly expressed in renal tubular epithelial cells and podocytes.With the aggravation of pathological injury in renal tubulointerstitial tissue,VEGF expression was decreased in model group.In different times in model group,the expressions of TGF-β1 in renal tubulointerstitial tissue and tubule were positive correlation (r_s=0.940,P<0.01).The expression of VEGF in renal tubule was negative correlation with the expression of TGF-β1 in renal tubule (r_s=-0.945,P<0.01) and TSP-1 in renal tubulointerstitial tissue (r_s=-0.923,P<0.01).Conclusions:The increase of TSP-1-TGF-β1 axis expressions enhanced renal interstitial fibrosis and development,the TSP-1 may play an important role in adenine induced chronic renal failure;the decline of VEGF expression also led to renal interstitial fibrosis.

HTML全文

参考文献(0)

施引文献

资源附件(0)