The Effects Of Perindopril And Atorvastatin On AngⅡ In The Brains Of Rabbits With Hypercholesterolemia And The Protective Effects Against Oxidative Stress

ObjectiveTo establish model of rabbit with hypercholesterolemia-atherosclerosis and observe the expression of angiotensinⅡ(AngⅡ) and heme oxygenase-1(HO-1),the activity of SOD,the amount of MDA in the brain tissues. We will investigate the influence of Perindopril and Atorvastatin to them.MethodsThirty-two healthy male New-Zealand albino rabbit were divided into four groups randomly: (Group A) Normal control(n=8); (Group B) high cholesterol diet(n=8); (Group C) high cholesterol diet and Perindopril(0.5mg/kg/day)(n=8); (Group D) high cholesterol diet and Atorvastatin(2.5 mg/kg/day)(n=8).After feeding for eight weeks, we will collect the empty stomach blood samples of these rabbits through central artery at awake state at the end of eight weeks (fasting about twelve hours), centrifugalization(3000rpm, 10min), blood serum was stored at -20℃and evaluate the density of the total cholesterol(TC)and low density lipoprotein(LDL)by BackmaanLX20 automatic biochemistry analyzer. To observe carotid artery and brain tissue by pathomorphology observation. To determine the expression of AngⅡand HO-1 by immunohistochemistry and the results were demonstrated by Positive Unit(PU); To determine the expression of HO-1 by Western blot and the results were demonstrated by average optical; To determine the activity of SOD and the amount of MDA by spectrophotometric method.Result1)The level of TC and LDL:The level of TC and LDL in B Group and C Group is increased significantly compared to A group(P<0.05); The level in D group is decreased significantly compared to B group(P<0.05),while there is no significant differences in D group compared to A group(P>0.05), There is no significant differences in C group compared to B group(P>0.05).2)The AngⅡexpression of brain tissue:The AngⅡexpression of B Group is increased significantly compared to A group(17.07±2.74 vs 5.24±1.26, P<0.05);The AngⅡexpression of C Group is decreased significantly compared to B group(12.40±1.44 vs 17.07±2.74, P<0.05),while is still increased than A group(12.40±1.44 vs 5.24±1.26 , P<0.05);The AngⅡexpression of D Group is decreased significantly compared to B group (15.32±1.68 vs 17.07±2.74, P<0.05),while is still increased than A group(15.32±1.68 vs 5.24±1.26, P<0.05).3)The HO-1 expression of brain tissue:The HO-1 expression of B Group is increased significantly compared to A group(immunohistochemistry:16.20±2.33 vs 6.16±2.05;Western-blot:0.68210±0.001853 vs 0.41820±0.001874,P<0.05);The HO-1 expression of C Group and D Group is increased significantly compared to B group(immunohistochemistry:21.65±2.26,24.26±3.04 vs 16.20±2.33;Western-blot:0.81040±0.001265,0.91880±0.001549 vs 0.68210±0.001853, P<0.05).4)The level of SOD,MDA in brain tissue:The activity of SOD in B Group is decreased significantly compared to A group(271.79±13.46 vs 424.03±14.45,P<0.05), but the amount of MDA is increased significantly compared to A group(40.87±2.78 vs 16.66±2.55,P<0.05);The activity of SOD in C Group and D Group is increased significantly compared to B group(375.34±9.41 ,402.38±7.35vs 271.79±13.46,P<0.05), but the amount of MDA is decreased significantly compared to B group(32.13±2.46, 21.57±2.19 vs 16.66±2.55,P<0.05).Conclusion1) The expression of AngⅡin brain tissue is increased significantly in cholesterol diet Group compared to Normal control Group; That explains RAAS in brain tissue is activated when hypercholesterolemia taking place. Perindopril and Atorvastatin can inhibit RAAS, and cut down the AngⅡexpression of rabbit atherosclerosis model.2) The brain tissue is at the state of oxidative stress when AS taking place. Perindopril and Atorvastatin can alleviate this oxidative stress damage on brain tissue and step down the proceeding of AS.