| Objective Renal injury induced by abdomen radio-therapy, known as radiation nephropathy, is one of the serious complications of this therapy. The pathological characteristics and mechanisms of radiation nephropathy have not been fully understood. Renal osteodystrophy is characterized by various in pathological representations and mechanisms. The present study has established a rat model of renal osteodystrophy by directly irradiation of both kidneys with γ rays. Meanwhile, the primary renal tubule cells and osteoblasts were used to study the pathological characteristics of kidney and bone as well as the possible cellular molecular mechanisms of this disease. By doing so, it is hoped to provide some useful information for preventing and therapy of this disease. Methods Rat model of irradiation-induced renal injury was established by subjecting both kidneys to 15 Gy Cs137 γ-rays after surgical exposure. 5/6 nephrectomy model was used as compare. Serum and urinal parameters were analyzed by means of RIA, MIA and autoanalyzer. Pathological characteristics of kidneys and bones were studied by light microscope, SEM and TEM. Bone mineral density of lumbar and femurs were determined by DEXA and physical density detector. The dry weight and ash weight of lumbar and femurs were measured. Decalcified slides of lumbar and un-decalcified slides of tibia were made for bone histomorphometry. Biomechanical property of lumbar and femurs were also detected. The mRNA level of TGF-β,OPN,IGF-I,COL-I,VDR,1α-hydroxylase and 24- hydroxylase in the kidney and of TGF-β,OPN,IGF-I,COL-I,VDR,OPG and RANKL in the bone were determined by RT-PCR. The protein level of TGF-β,OPN,IGF-I was determined by Western blot. Primary renal tubule epithelial cells were subjected to 1Gy,5Gy,10Gy γ rays, as well as to PTH(1～34) and 25(OH)D3.The effects of these factors on proliferation and function of renal tubule epithelial cells were studied. Finally, the effects of culture medium of renal tubule epithelial cells on proliferation and function of primary osteoblasts were studied.Results Irradiation of both kidneys with 15 Gy Cs137 γ-rays resulted in progressive letdown of renal function, especially of tubule function. The pathological exhibition includes reducing in mass, swell of glomerular, that Bowman's capsules straitened or disappeared, and some epithelia denaturalized or died. The Mitochondria of tubule epithelial cells were tumefied and the cristae were shortened, lessened and disordered. Progressive fibrosis in renal matrix was found. The mRNA and protein level of TGF-β1 were augmented. The mRNA level of 1α-hydroxylase,24 –hydroxylase and VDR was decreased. The dry weight and ash weight, BMD of femur and lumbar were significantly reduced. TV/BV,Tb.Th,Tb.N of tibia and lumbar were distinctly decreased and Tb.Sp was increased. The mRNA level of TGF-β1,IGF-I,OPN in bone was increased, and the ratio of RANKL/OPG was increased. The maximum load of lumbar and femur were significantly reduced. In the serum, PTH,total ALP were increased and 1,25(OH)2D3 was significantly decreased. The Pyd/Cr in urine was increased. Treating rat with BONE-ONE after irradiation had little effect on renal function and structure, but could result in increasing in bone mass and bone biomechanical property. Irradiation of renal tubule cells with 1Gy,5Gy,10Gyγ-rays resulted in decreasing in proliferation and cell number. The mRNA level of 1α-hydroxylase and 24 –hydroxylase were also reduced, while TGF-βmRNA level was increased. PTH(1～34) significantly suppressed proliferation of tubule epithelial cells, while promoted expression of 1α-hydroxylase and suppressed expression of 24-hydroxylase. 25(OH)D3 had little effect on proliferation of tubule epithelial cells, but promoted expression of 24-hydroxylase and suppressed expression of 1α-hydroxylase. The culture medium of renal tubule epithelial cells significantly promoted proliferation and differentiation of osteoblasts, enhanced expression of related genes (and), reduced the ratio... |
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