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Experimental Study on the Effect of TSP-1 on the Activation of TGF-β1 in Chronic Allograft Nephropathy

Author: MiYongJie
Tutor: WuXiongFei
School: Third Military Medical University
Course: Surgery
Keywords: Chronic allograft nephropathy Kidney transplantation TGF-β1 Thrombospondin-1
CLC: R692.9
Type: Master's thesis
Year: 2005
Downloads: 27
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Abstract


Objective: To investigate the expression of TSP-1 in CAN rats and the effect of TSP-1 on the activation of TGF-β1, and whether inhibiting TSP-1-mediated activation of TGF-β1 could delay the progression of renal fibrosis in CAN.Methods:Naive male inbred Lewis (LEW, RT1) rats and Fisher rats(F344, RT1v1)were used respectively as recipients and donors of kidney allografts in the standard Fisher/Lewis kidney transplant model of CAN. The uninephrectomized Fisher rats were used as controls. All the rats were divided into three groups and treated simultaneously with one of the following regimens: (i) Uninephrectomized group(n=6): 0.5 ml saline i.p. daily ; (ii) SLKL-untreated group(n=10): 0.5 ml saline i.p. daily; (iii) SLKL-treated group (n=10):100μg SLKL in 0.5 ml saline i.p. daily. Serum creatinine and 24h urinary protein excretion were determined every 4 weeks until the end of the experiment. Sixteen weeks after renal transplantation, secreted active and total TGF-β1 in renal allograft tissue supernatant were detected by a well-established bioassay system using mink lung epithelial cells. The paraffin sections were stained with hematoxylin and eosin (HE)/periodic acid-Schiff (PAS) to analyze pathological changes and the expression of TGF-β1, TSP-1 andα-SMA by immunohistochemistral staining. The mRNA production of TSP-1 was evaluated by semiquantitative reverse transcription-PCR.Result:1 . Survival:Six in LSKL-untreated group died during the experiment, one in LSKL-treated group died, no one died in uninephrectomized group.2.Allograft function: Renal function, as indicated by serum creatinine and proteinuria, was markedly different between the two groups(LSKL-untreated and LSKL-treated group). The serum creatinine of LSKL-untreated group began to increase 8 weeks after transplantation and continued to increase thereafter. In contrast, the serum creatinine of LSKL-treated group remained stable. The mean serum creatinine of surviving recipients in

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CLC: > Medicine, health > Surgery > Urology ( urinary and reproductive system diseases) > Kidney disease > Other diseases
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