Inhibition Of Early Atherogenesis By Telmisartan And Rosiglitazone In Male Rats With Diabetes Mellitus

Objective Diabetic macrovascular complicaton is one of the most common complication of the type-2 DM, which is also the main reason leading to be disabled or die. Artherosclerosis(AS) is a independent risk factor and one of the main reason caused the diabetic macrovascular complication and promoted it, however, the initial change of the atherosclerosis is the damage of the vascular endothelial cell. The anti-atherosclerosis drug application, has a very important significance for prevention and treatment of heart and cerebrovascular diseases. This research takes SD rats who has similar AS formation with human being as example,to observe the expression of PPAR-γ,VCAM-1 and ICAM-1 on the arterial vessel wall and the changes of the monocytes infilitrating under the intima when early AS occurs. The objective is to identify the effects of telmisartan and rosiglitazone on early atherogenesis in male rats with type 2 Diabetes Mellitus and to discuss the mechanism as the theoretical suport for T2DM early AS treatment.Method The rat model who had early atherogenesis in atery was established by high-fat, high-sugar feeding[2]. Forty SD rats were divided into four group radomly. Group A was the rats with normal control (Group NC). Group B was the rats with Type 2 diabetes mellitus(Group T2DM). Group C was the rats with T2DM intervened with Rosiglitazone maleate(Group RGZ). Group D was the rats with T2DM intervened with telmisartan (Group TM). There was 10 rats for each group. Group B, C and D were feeded with high-fat and high-sugar food (10% lard,20% sucrose,2.5% cholesterol,1% sodium cholate and 66.5% conventional feed) and fructose water (12%). One month later,the rats were shot sigle dose of 25mg/kgSTZ(made by 0.1mol/L citrate buffer preparation with pH4.2, the concentration is 0.25%) intraperitoneal injection after fasting for 24 hours. Group A was shot citrate buffer. Group C was taken intragastric administration with 5mg/kg·d Rosiglitazone maleate. Group D was taken intragastric administration with telmisartan.The intragastric administration was done 2 times per day at morning and night. Group A and B were taken intragastric administration with saline as control. All rats were raised in 4 cases according to the standard.of clean grade animal. The probation last 16 weeks.Results:Compared with the control group, the level of TC,TG,LDL-C,BG in blood were increase significantly (P<0.01) in type 2 Diabetic group. The telmisartan and rosiglitazone treatment decrease blood TC, TG, LDL-C and BG. The expression of PPARγin type 2 diabetic group, telmisartan and rosiglitazone group had significant differences compared with the control group, but there wasn't any significant differences (P>0.05) among those three groups. Expression of VCAM-1,ICAM-1 and the monocytes infilitrating into the intima of the aortas telmisartan and rosiglitazone group was significantly lower than those in diabetic group(P<0.01). The endothelial damage of the aortas in telmisartan and rosiglitazone group was less severe than that in diabetes mellitus group.Conclusion:telmisartan and rosiglitazone can prevent early atherogenesis through alleviating the damage to the arterial wall by increasing the activation of PPAR-γand inhibiting the VCAM-1,ICAM-1 expression and the monocytes infilitrating into the arterial wall.