The renal protective effects of cilostazol on suppressing pathogenic thrombospondin-1 and transforming growth factor-beta expression in streptozotocin-induced diabetic rats.
Diabetic nephropathy is a major complication facing patients with diabetes mellitus. The renal protective effects of the phosphodiesterase III inhibitor, cilostazol, were investigated in rats with streptozotocin-induced diabetes. Expression of thrombospondin-1 (TSP-1) and transforming growth factor-beta (TGF-beta) in the kidney was measured by immunohistochemistry and real-time reverse transcription-quantitative polymerase chain reaction analysis in diabetic rats, cilostazol-treated diabetic rats and control rats. Ultrastructural changes in the kidney were also analysed using microscopy. Four weeks after the induction of diabetes, TSP-1 and TGF-beta expression was significantly increased in the kidneys of diabetic rats compared with the control and was significantly lower in cilostazol-treated diabetic rats than in the untreated diabetic rats. Microscopy revealed characteristic renal pathology in the diabetic group, which was rarely seen in the cilostazol-treated diabetic rats. In conclusion, this study indicates that cilostazol treatment of diabetic rats effectively prevents pathological kidney changes, possibly via the down-regulation of TSP-1 and TGF-beta expression compared with untreated rats.
Wang
X
X
The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yan
L
L
Chen
W
W
Xu
L
L
Zhang
X
X
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D007668:Kidney / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000494:pharmacology; D013777:Tetrazoles / Q000627:therapeutic use*; D019700:Thrombospondin 1 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D001786:Blood Glucose; D012333:RNA, Messenger; D013777:Tetrazoles; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D013311:Streptozocin; D000077407:Cilostazol