The Islet Cells Protective Effect Of Irbesartan Intervention On Oxidative Stress And Apoptosis Of Islet Cells In Islet Cells Apoptosis Model

Objective:Establish acute islet β cell apoptosis model in mice by streptozotocin in a low, non-diabetogenic dose, To observe effects of irbesartan intervention on oxidative stress and apoptosis of islet β-cells in islet β-cells apoptosis model.Methods:BABL/C mice were injected intrapertoneally with a single different-dose of stceptozoein(STZ)(60mg/kg、80mg/kg、100mg/kg).The changes of blood glucose and the result of TUNEL were monitored,the tissue sections of pancreas were stained by HE after 6h、12h and 24h.Irbesartan+ STZ group fed a week later to be 300mg/kg Irbesartan then injection of 80mg/kg STZ; STZ group were injected with 80mg/kg STZ. HE、immunohistochemistry、 TUNEL would be monitored, using real-timePCR detected AT1R, Caspase3, P38MAPK, ROS and NADPH mRNA expression.Result:(1) At all test time points, glucose levels ranged between 6-llmmol/L, which were below the level of diabetes model. The highest rate of apoptosis occurred in 12h.Compared with the control group were significantly elevated blood glucose (P<0.000), but the blood glucose level<10mmol/L. compared with the control group。Islet cell apoptosis rate of STZ group and irbesartan group were increased (P<0.001); Compared with STZ group, irbesartan+ STZ group apoptosis rate decreased significantly (P<0.001). (2) expression of insulin in Irbesartan+ STZ group compared with STZ group increased significantly(P<0.001).AT1R、Caspase3 mRNA and oxidative stress-related indicators P38MAPK、ROS、NADPH mRNA expression up-regulation in STZ group(P<0.05). After irbesartan intervened that showed a significant downward trend (P<0.05).Conclusion:(1) Establish acute islet βcell apoptosis model in mice by streptozotocin in a low, non-diabetogenic dose streptozotocin is successful within the compensatory of islet. The highest rate of apoptosis occurred in 12h after intervention.Irbesartan can reduce islet β cell apoptosis. (2)STZ can induce islet cells ATIR expression increased, therefore islet cell apoptosis and injure by activation of RAS system. As well as elevated levels of oxidative stress and increased apoptosis, and irbesartan protreatment can reduce oxidative stress and apoptosis and to protect the islet cells.