Experimental study on protective mechanism of the combined treatment of pyrrolidine dithiocarbamate and mycophenolale mofetil on kidneys of diabetic rats / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate protective effects of pyrrolidine dithiocarbamate (PDTC) and mycophenolate mofetil (MMF) on kidneys of diabetic rats and the possible mechanism. Methods Thirty-four streptozotocin-induced diabetic rats were randomly divided into 4 groups diabetic aminals without treatment (D group), diabetic rats treated with PDTC (P group), diabetic rats treated with MMF (M group), diabetic rats treated with combined PDTC and MMF (P+M group), and normal rats were considered as control group (C group). Blood glucose, blood urea nitrogen (BUN), serum creatinine (Scr), and 24 h urinary protein (24 h UP) were detected at the end of treatment lasting for 8 weeks. Kidneys were weighed in order to measure kidney weight/body weight ratio (KI) after rats were killed. Pathological changes in the kidneys were observed by light microscope and electron microscope. Expressions of interleukin-18 (IL-18), intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in renal glomerulus were detected by immunohistochemical staining.Results Blood glucose, BUN, Scr, 24 h UP, KI were significantly higher in D, P, M and P+M groups than those in C group (all P＜0.05). BUN, Scr, 24 h UP, KI were significantly lower in P, M and P+M groups than those in D group (all P＜0.05). 24 h UP was reduced in P+M groups compared with P,M groups (P＜0.05). Pathological changes were attenuated in P,M and P+M groups compared with D group. Expressions of IL-18, ICAM-1, TNF-α in renal glomerulus were much higher in D group than those in C group (all P＜0.05) and were reduced in P, M and P+M groups compared with D group (all P＜0.05). Expressions of IL-18, ICAM-1, TNF-α in P+M group were lower than those in P group (all P＜0.05), while expressions of IL-18, TNF-α were lower than those in M group (both P＜0.05). Conclusion The protective effects on kidneys of diabetic rats produced by combined use of PDTC with MMF were much better than by the application of either PDTC or MMF alone. The mechanism appears to be related with suppressing expressions of inflammatory cytokines.