| ObjectiveTo establish rabbit high cholesterol atherosclerosis model and observe the expression of AngⅡ(AngiotensinⅡ) ,NF-κB(Nuclear factor Kappa B) and the activity of iNOS (inducible nitric oxide synthase) in brain tissue , investigate the influence of Perindopril﹑Valsartan and Atorvastatin to the three above index and the possible mechanisms.Methodsforty healthy male New-Zealand white rabbit were divided into five 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 Valsartan(10mg/kg/day)(n=8); (Group E) high cholesterol diet and Atorvastatin(2.5 mg/kg/day)(n=8).After feeding for eight weeks, Collecting the empty stomach blood preparation through central artery at awake state at the end of eight weeks (fasting diet 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. the expression of AngⅡin brain tissue were examined by immunohistochemistry, the expression of NF-κB were detected by Western blot and immunohistochemistry, the activity of iNOS were measured by chemical colorimetry assay.Result(Group A)Normal control ; (Group B) high cholesterol diet ; (Group C) high cholesterol diet and Perindopril; (Group D) high cholesterol diet and Valsartan; (Group E) high cholesterol diet and Atorvastatin .the five groups were compared:⑴The level of TC and LDL:The level of TC and LDL in Group B,Group C and Group D is increased significantly compared to A group(P<0.05); There is no significant differences in the three group(P>0.05);The level in Group E is decreased significantly compared to B group (P<0.05),while there is no significant differences in Group E compared to A group(P>0.05);⑵immunohistochemistry:The AngⅡexpression in five groups respectively: 5.2±1.3,17.1±2.7,12.40±1.44,17.24±1.51,15.3±1.7;The NF-κB expression respectively: 9±1.6,22.2±2.6,12.64±1.39,14.34±2.30,9.5±1.16,The NF-κB expression in the three Medication groups is decreased significantly compared to AS group ( P <0.01) . The AngⅡexpression of Perindopril Group and Valsartan Group is lower than high cholesterol diet Group( P <0.01), The AngⅡexpression of Valsartan Group have no difference with high cholesterol diet Group( P>0.05);⑶Western blot: optical density of NF-κB respectively:0.5621±0.0024,0.9988±0.0041,0.6821±0.0027,0.6805±0.0031,0.5810±0.0020,The NF-κB expression of high cholesterol diet Group is higher than the rest four Groups( P <0.01);⑷the activity of iNOS respectively: 3.4±0.4,10.0±0.9,5.55±0.53,5.51±0.65,4.8±0.6,the activity of iNOS in the three Medication groups is lower than in the high cholesterol diet Group( P <0.01),but higher than Normal control Group(P <0.01)Conclusion1)The AngⅡexpression of in brain tissue of High-Cholesterol Atherosclerotic Rabbits is higher than Normal control Group. That explain brain tissue RAAS is at the state of activation when AS taking place.2)the expression of NF-κB(Nuclear factor Kappa B) and the activity of iNOS (inducible nitric oxide synthase) in brain tissue increased in AS. That explain there is inflammatory activator expression when AS taking place.3)Perindopril or Valsartan could decrease the expression of NF-κB, iNOS, So could ameliorate the lesions of brain tissue through interrupting RAS activiation.4)Atorvastatin. can significantly decrease the content of AngⅡ,NF-κB and iNOS. It suggests that Atorvastatin can inhibite brain tissue RAAS and alleviate the brain injury induced by inflammation following high cholesterol... |
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