The Role Of Mitochondrial-Cyto C-caspase 9 Pathway In The Development Of Renal Tubular Epithelial Cell Apoptosis Of The Rats With Hyperoxaluria

Objective To investigate the role of Mitochondrial-Cyto C-caspase 9 pathway in the development of renal tubular epithelial cell apoptosis of the rats with hyperoxaluria.Methods Twenty four male grow-up wistar rats were divided into four groups at random, with six rats in each. The groups were named Normal Control Group, Hyperoxaluric Group, Interventional Control Group and Ciclosporin A (CsA)Interventional Group. The rats were sacrificed in 4 weeks after ephrectomy was then performed. The tissue sections obtained from kidneys that were examined under light microscopy for presences and degrees of Oxalate crystal deposition in the tubular lumina. Apoptotic changes in renal tubular cells were examined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick and labeling (TUNEL) method. Change of renal cytoplasmic Cytochrome C (Cyto C) was analyzed the means of Western blot. Expressions of Caspase 3 and Caspase 9 were examined by the method of the immunohistochemistry.Results Oxalate crystal deposition was evident in the renal tubular lumen in the Hyperoxaluric Group and the CsA Interventional Group, while there was no evidence in groups the Normal Control Group and the Interventional Control Group. Compared with other 3 groups, apoptic index (AI) in the Hyperoxaluric Group was increased obviously. The Cyto C, caspase 3(p20) and caspase 9(small) were enhanced more obviously (P<0.05). AI and the degree of protein expression of the CsA Interventional Group were less than the Hyperoxaluric Group (P<0.05), but more than the Normal Control Group and Interventional Control Group (P<0.05). Conclusions The Mitochondrial-Cyto C-caspase 9 pathway paticipates in the apoptosis of the renal tubular epithelial cell of rats with hyperoxaluria. Expressions of the Cyto C, Caspase 3(p20) and Caspase 9(small) were inhibited by CsA, and AI was also decreased by CsA.