title: Chymase inhibition protects diabetic rats from renal lesions.
abstract: The present study aimed to investigate the effects of a chymase inhibitor on renal injury in diabetic rats. A total of 24 Sprague-Dawley rats were randomly divided into the following groups: The control group (n=7), the diabetes group (DM group; n=7), and the DM + chymase inhibitor group (DM + Chy‑I group; n=10). Diabetes was induced via an intraperitoneal injection of streptozotocin (65 mg/kg). Rats in the DM + Chy‑I group were administered 1 mg/kg chymase inhibitor [Suc-Val-Pro-PheP-(OPh)2] daily for 12 weeks by intraperitoneal injection. Subsequently, kidney weight, various biochemical parameters and blood pressure were measured. In addition, the expression levels of fibronectin (FN), type IV collagen (ColIV), transforming growth factor (TGF)‑β1 and vascular endothelial growth factor (VEGF) were determined by immunohistochemistry and reverse transcription polymerase chain reaction. Compared with in the DM group, the levels of serum cholesterol and urinary albumin/creatinine were decreased in the DM + Chy‑I group (P<0.05). Furthermore, chymase inhibition reduced the overexpression of FN, ColIV, TGF‑β1 and VEGF (P<0.05) in the renal tissue of diabetic rats. These results indicated that chymase inhibition may reduce the excretion of urinary albumin and the deposition of extracellular matrix components in the kidney of diabetic rats. These effects may be mediated by altered expression of the VEGF and TGF‑β1 pathways. In conclusion, chymase inhibition may be considered a potential method for the treatment of renal damage.
authors.affiliation: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D053818:Chymases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D020011:Protective Agents; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D053818:Chymases