ABSTRACT
Aim To evaluate the reno-proteetion of saxagliptin combined with metformin in mice with T2DM anrl its relationship with redox balance.Meth¬ods C57BL/6J mice were fed with high fat diet and injected with low dose STZ intraperitoneally to establish T2DM mouse model.Then they were randomly divided into T2DM group, glibenclamide group ( Gli group), metformin group ( Met group) , saxagliptin group ( Sax group) and saxagliptin + metformin group ( S + M group) , and normal control group ( NC group) with 8 mice in each group.Eight weeks after intervention the mice were weighed.Blood, urine and renal tissue sam¬ples were collected to measure GHbA,c, FBG, Alb, 8-OHdG, 8-iso-PG, SOD, GSH, GSSG and Ucr.The pathological morphology of renal tissues in each group was observed.Results Saxagliptin combined with metformin reduced significantly the levels of Alb/Ucr ( UACR) , 8-0HdG/Ucr( UOCR) , 8-iso-PG/Ucr( UP- CR) , increased the activity of SOD and GSH/GSSG ratio, and improved the pathological changes of renal tissues, which were superior to those in Met group and Sax group.Conclusions Saxagliptin combined with metformin have a synergistic protective effect on the kidneys of type 2 diabetic mice.The mechanism is partly related to alleviating oxidative stress and impro¬ving redox balance in vivo.
ABSTRACT
Objective To compare the characteristics of ulcer wound healing in current commonly used C57BL/6J-db/db mouse models of spontaneous gene mutation-induced type 2 diabetes and in C57BL/6J mice with diabetes induced by streptozotocin (STZ), and to provide a basis for related experimental studies on diabetic ulcer in animal models.Methods To establish the mouse models of diabetic ulcer wound, observe the healing time and calculate the wound healing rate at 0, 3, 5, 7, 10, 14 days.Tissue samples were collected at days 7 and 14.HE and Masson staining, and immunohistochemistry (CD31 and PCNA) were used to observe the pathological changes of the wound tissues.Gene expressions of collagen-IIIα, fibronectin and α-SMA were detected by fluorescent quantitative analysis.Results The wound healing time of db/db mice was significantly delayed compared with the STZ mice, which was extended from 16.6±0.8 d to 20.2±1.3 d (P< 0.001).Compared with the STZ group, the growth of granulation tissue in the db/db group was slow, the length of newly formed epithelium was insufficient, the collagen deposition was disordered, and the wound healing was poor.At 7 days, the expression of CD31 and PCNA was significantly lower in the db/db group (P< 0.01), and at 7 and 14 days, the increase of collagen-IIIα and α-SMA genes up-regulation was significantly lower in the db/db group than in the STZ group.Conclusions Both the two types of diabetic mice show delayed wound healing.However, compared with the STZ-induced diabetic mice, the gene mutation db/db mice are more suitable for studies of diabetic ulcer wound healing as regarding the extent of the delay and the degree of difficulty of wound healing.