| Background and Objective Chronic renal allograft failure has been one of themost common causes of end stage renal disease, and chronic allograft nephropathy (CAN) is the most prevalent cause of renal allograft failure in the first post-transplant decade. Morphological findings associated with CAN include glomerulosclerosis, widespread obliterative vasculopathy, progressive interstitial fibrosis and tubular atrophy. No effective treatment for fibrotic and sclerotic lesions is available, however, active intervention in early stages may retard renal-function loss and ameliorate renal fibrosis and sclerosis. It has been urgent to detect and eliminate early signs of chronic allograft loss. Several experimental models including retransplantation studies by Tullius et al confirmed the concept of early period chronic allograft nephropathy, which indicates a reversible lesion, particularly mononuclear cell infiltration and vascular smooth muscle cell proliferation and migration. The basis of molecular pathology of which is that cells leave their original position and migrate to another, in which matrix remodeling plays a pivotal role. It's widely believed that matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases(MMPs/TIMPs) system is crucial for matrix remodeling. It's reasonable for us to propose the following hypothesis: in the early period CAN, MMPs/TIMPs system is a pivotal figure for mononuclear cell infiltration and vascular smooth muscle cell proliferation and migration through its effects on matrix remodeling, thusinfluences the late survival of allograft. To test it, we have established a rat model of early period CAN to explore the role of MMP-9 in this lesion.[Methods] Fisher(F344) rat kidneys were orthotopically transplanted into Lewisrecipients(n=10) and treated with cyclosporine A(1.5mg/kg/day) for the first 10 days following transplantation, whereas uninephrectomized Fisher rats(n=9) and Lewis rats(n=8) as vehicles. Kidneys were harvested 12 weeks after operation for morphological and immunohistologic analysis. HE, PAS and MASSON stainingwere performed , as well as TGF- P i and MMP-9 were immunostained by LSAB+ kit(DAKO Co. Ltd). [Results I By 12 weeks after engraftment, (1)the count of interstitial mononuclearcells in graft increased significantly(24.14 5.82/HP vs. 8.17 2.96/HP in LEWcontrol, P<0.001; and vs. 9.59 2.97/HP in F344 control, P<0.001, respectively), accompanied with significant increase of the count of vascular smooth muscle cells(12.01 2.21 vs. 7.01 1.94 in LEW control, P<0.00 1; and vs. 7.86 2.16in F344 control, P=0.001, respectively). However, there were no significant difference in the ratio of interstitial fibrosis between graft and controls(0.083 1 0.0261 vs. 0.0614 + 0.0269 in LEW control, and vs.0.0679 0.0228 in F344 control, F=1.810, P=0.185), neither in the quantity of urinary protein of 24 hours(0.0298 0.0046 vs. 0.0283 0.0028, and 0.0266 0.0021, F=2.126, P=0.141), and Banff "eg" score(x2=4.854, P=0.156). The concentration of serum creatinine in graft was 88.65+12.73 y mol/1 compared with 75.07 11. 37 mol/1 in F344 control(P=0.026) and 76.83 + 13.33 u mol/1 in LEW control(P=0.073). (2)At this time point, the immunostaining of TGF- 1 and MMP-9 in graft tubulointerstitium increased significantly compared with that in LEW control (0.5825 0.0998 vs. 0.3288 0.1069, P<0.001; and 0.3250 0.0919 vs. 0.1206 + 0.0466, P<0.001, respectively), as well as compared with that in F344 control(0.0583 0.0998 vs.0.3361 0.0953, P<0.001; and 0.3250 + 0.0929vs. 0.1 744 0.05 16, PO.001, respectively); So as the immunostaining in vessel wall(0.0860 0.0171 vs. 0.0644 + 0.0097, P=0.006; and 0.0947 0.0198 vs. 0.0489 0.0100, PO.001, respectively), (0.0860 + 0.0171 vs. 0.0703 + 0.0124,P=0.037 and 0.0947 0.0198 vs.0.0708 0.015, P=0.01, respectively). (3)Immunostaining of MMP-9 in graft tubulointerstitium and vessel wall was correlated with interstitial infiltration of mononuclear cell(r=0.757, P-0.011) an...
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