Integrated Treatment of Prostaglandin E1 and Angiotensin-Converting Enzyme Inhibitor in Diabetic Kidney Disease Rats: Possible Role of Antiapoptosis in Renal Tubular Epithelial Cells
Autor: | Yaqin Zhang, Yaru Mou, Jianjun Dong, Junyu Zhao, Xiaojun Zhou, Lin Liao, Zhongwen Zhang, Congcong Guo |
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Rok vydání: | 2018 |
Předmět: |
Male
Urinary protein medicine.medical_specialty Drug Evaluation Preclinical 030232 urology & nephrology Angiotensin-Converting Enzyme Inhibitors Apoptosis Disease 030204 cardiovascular system & hematology Diabetes Mellitus Experimental 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Genetics medicine Animals Diabetic Nephropathies cardiovascular diseases Alprostadil Rats Wistar Prostaglandin E1 Molecular Biology Endothelin-1 biology Diabetic kidney Angiotensin II Macrophages Epithelial Cells Angiotensin-converting enzyme Cell Biology General Medicine Renal Tubular Epithelial Cells Kidney Tubules Endocrinology chemistry Enzyme inhibitor biology.protein Nephritis Interstitial lipids (amino acids peptides and proteins) |
Zdroj: | DNA and Cell Biology. 37:133-141 |
ISSN: | 1557-7430 1044-5498 |
DOI: | 10.1089/dna.2017.3690 |
Popis: | To investigate the therapeutic mechanisms underlying prostaglandin E1 (PGE1) and angiotensin-converting enzyme inhibitor (ACEI) on reducing urinary protein in diabetic kidney disease (DKD). DKD rats were established and randomly divided into four groups: PGE1 (10 μg/kg/day) (P group), ACEI (10 mg/kg/day) (A group), combination of PGE1 with ACEI treatment (P + A group), and saline treatment group (DKD group). Untreated rats were used as normal control (N group). Urinary albumin, endothelin-1 (ET-1), angiotensin II (AngII), TUNEL assay, Masson's trichrome staining, and immunohistochemistry staining for CD68 were evaluated in all groups. Ten days after treatment, urinary albumin was significantly decreased in the P and P + A groups (p 0.01 vs. the DKD group). At the end of 8 weeks, the albumin was still significantly reduced in the P + A group (p 0.05 vs. the A group). ET-1 and AngII were also significantly decreased in three treatment groups (p 0.01 vs. the DKD group), especially in the P + A group. Few cells underwent apoptosis in glomerular regions in DKD rats, while amounts of apoptotic cells were seen in tubules regions. Further, apoptosis and the areas of fibrosis in tubulointerstitial were both decreased most in the P + A group compared with the DKD group. Apoptosis of renal tubular epithelial cells may participate in the development and progression of DKD in rats. Combination of PGE1 with AGEI remarkably protects renal function compared with PGE1 or ACEI monotherapy. The potential therapeutic mechanisms of PGE1 and AGEI might be via multiple targets and, at least in part, through inhibiting the apoptosis of renal tubular epithelial cells. |
Databáze: | OpenAIRE |
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