Effects of the combined use of benazepril and valsartan on apoptosis in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis.
- Author:
Ziming HAN
1
;
Yan XING
;
Hongwei WANG
;
Xiuling LIANG
;
Jianhua ZHOU
Author Information
1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
- Publication Type:Journal Article
- MeSH:
Angiotensin II Type 1 Receptor Blockers;
administration & dosage;
Angiotensin-Converting Enzyme Inhibitors;
administration & dosage;
Animals;
Apoptosis;
drug effects;
Benzazepines;
administration & dosage;
Doxorubicin;
Drug Therapy, Combination;
Fas Ligand Protein;
Glomerulosclerosis, Focal Segmental;
chemically induced;
drug therapy;
pathology;
Kidney;
pathology;
Male;
Membrane Glycoproteins;
biosynthesis;
genetics;
Random Allocation;
Rats;
Rats, Sprague-Dawley;
Tetrazoles;
administration & dosage;
Tumor Necrosis Factors;
biosynthesis;
genetics;
Valine;
administration & dosage;
analogs & derivatives;
Valsartan;
fas Receptor;
biosynthesis;
genetics
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2004;24(3):254-258
- CountryChina
- Language:English
-
Abstract:
The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin II type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.