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  • Title: [Effects of rhein on activity of caspase-3 in kidney and cell apoptosis on the progression of renal injury in glomerulosclerosis].
    Author: Ji ZQ, Huang CW, Liang CJ, Sun WW, Chen B, Tang PR.
    Journal: Zhonghua Yi Xue Za Zhi; 2005 Jul 13; 85(26):1836-41. PubMed ID: 16253190.
    Abstract:
    OBJECTIVE: To investigate the effects of rhein on the progression of renal injury and cell apoptosis in glomerulosclerosis, and further explore the protective mechanism of rhein on glomerulosclerosis. METHODS: Glomerulosclerosis models were made for SD rats by unilateral nephrectomy and being injected with Adriamycin into caudal vein, and randomly divided into control group, renal disease group, Rhein treatment group and Benazepril treatment group, and 6 rats in each group were killed at the 6th, 8th, 10th, 12th week respectively. The apoptosis protease-3 (caspase-3) in renal cortex was determined by immunohistochemistry stain method, and the activity of caspase-3 was measured by colorimetry, and the activity of nuclear factor-kappa B (NF-kappaB) was analyzed by gel electrophoretic mobility shift assay (EMSA), and renal tissue cell apoptosis was tested by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) in order to observe expressions of caspase-3 and NF-kappaB and cell apoptosis of renal tissue. RESULTS: Renal disease group presented with distinct proteinuria, decreasing of blood albumin content and increasing of cholesterol concentration. Glomerulosclerosis index, apoptosis index, activity of NF-kappaB and expression of caspase-3 in renal disease group were more significantly higher than those in control group (P < 0.05 or P < 0.01) as time passed. Compared with the other time points in renal disease group, there were a great number of TUNEL-positive cells observed at the 10th week, slightly higher than that at the 12th week (9.3 +/- 2.3 vs 8.4 +/- 1.2, P > 0.05), the expression of Caspase-3 was also most obvious at the 10th week, significantly higher than that at the 12th week (11.4 +/- 2.5 vs 8.2 +/- 1.7, P < 0.05), which mainly located around capillary vessel in renal cortex, tending to be consistent with apoptosis cells expression. After the 8 weeks treatment of rhein or Benazepril, the number of TUNEL-positive cells significantly decreased and maintained at a certain level, and the activity of NF-kappaB and expression of caspase-3 decreased (P < 0.05), and renal pathological changes and biochemical changes improved magnificently, moreover, the expression of caspase-3 showed positive correlation with apoptosis index (r = 0.836, P < 0.01). CONCLUSION: Rhein could have significant protective effects on the progression of renal injury, and might regulate pathological changes by influencing the activities of NF-kappaB and caspase-3 in the early phase of glomerulosclerosis. Therefore, down-regulating caspase-3 expression in kidney might be one of the molecular mechanisms in the way that rhein could alleviate renal tissue cell apoptosis in glomerulosclerosis.
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