Objective To investigate the inhibitory effects of rosiglitazone on the synthesis of reactive oxygen species (ROS) and the expression of monocyte chemoattractant protein 1 (MCP-1) induced by high glucose in rat mesangial cells. Methods The mesangial cells were divided into six groups: control group ( C, 5.6 mmol/L glucose), mannitol group (M, 24.2 mmol/L mannitol+group C), high glucose group( H, 30 mmol/L glucose), R1 group(R1, group H+10 μmol/ L rosiglitazone), R2 group (R2, group H+20 μmol/L rosiglitazone), N-acetylcysteine (NAC) group (N, group H+5 mmol/L NAC, NAC was added 1 h before the stimulation of high glucose). The level of ROS was measured by confocal laser scanning microscopy. The mRNA and the protein expression of MCP-1 were semi-quantitatively determined with reverse transcription-polymerase chain reaction and ELISA respectively. Results No significant differences of ROS and MCP-1 were found between control group and mannitol group. The intracellular ROS induced by high DOI:10.3760/cma.j.issn. 1001-7097.2009.01.011glucose increased by 4.1-fold compared to control group (P<0.01), which was prevented by rosiglitazone (20 μmol/L) and NAC respectively. The MCP-1 mRNA expression in group R2 and group N was significantly lower than that in group H (P<0.01). The MCP-1 protein level in group H [(940.9±20.3) ng/L] was higher than that in group C [(403.0±8.1) ng/L] (P<0.01), and the expression of MCP-1 protein in group R2 [(562.5±15.3) ng/L] and group N [(539.8±8.3) ng/L] was lower than that in group H (P<0.01). Conclusion Rosiglitazone may suppress high glucose-induced MCP-1 expression by reducing the level of ROS, which may be one of the mechanisms that rosiglitazone plays a direct role in the protection of kidney.

Objective To study the therapeutic value of Mongolian drug hatagaqi-7 for wound healing of diabetic ulcers in rats and preliminarily explore its molecular mechanism in regulating hypoxia-inducible factor-1α(HIF-1α).Methods Adult male SD rats were randomly divided into control,diabetes,Mongolian drug,and cytokine groups.Except in the control group,the other three groups were treated with an intraperitoneal injection of streptozotocin to establish the diabetes model.Ulcer wounds were prepared in the mouse back of the four groups.One week later,the Mongolian drug group was treated with hatagaqi-7,and the cytokine group was treated with recombinant bovine basic fibroblast growth factor for 2 consecutive weeks.Fasting blood glucose(FBG),wound area,wound pathology,expression levels of advanced glycation end products(AGEs),receptor of AGE(RAGE),HIF-1α and vascular endothelial growth factor(VEGF),secreted levels of interleukin-1β(IL-1β),interferon-γ(IFN-γ),and malondialdehyde(MDA),and the total antioxidant capacity(T-AOC)were assessed.Results FBG of diabetes,Mongolian drug and cytokine groups was higher than that in the control group(P<0.05),and no significant difference was observed among the three groups(P>0.05).Compared with the control group,the ulcer wound area,scope of unrepaired tissue,expression levels of AGEs and RAGE,and secreted levels of IL-1β,IFN-γ,and MDA in wound tissue of the diabetes group were increased,and T-AOC and expression levels of HIF-1α and VEGF of the diabetes group were decreased(P<0.05).Compared with the diabetes group,the ulcer wound area,scope of unrepaired tissue,expression levels of AGEs and RAGE,and secreted levels of IL-1β,IFN-γ,and MDA in wound tissue of Mongolian drug and cytokine groups were decreased,T-AOC and expression levels of HIF-1α and VEGF in Mongolian drug and cytokine groups were increased(P<0.05),and indexes of the Mongolian drug group were better than those of the cytokine group.Conclusions Mongolian drug hatagaqi-7 promotes ulcer wound healing in diabetic rats,the inhibiton of AGE and RAGE expression and induction of HIF-1 α are the possible molecular mechanism.