Mechanism Of Sesamin On Improving Oxidative Stress In Hippocampus And Cerebral Cortex Of Spontaneously Hypertensive Rats

Objective : To explore the underlying mechanisms involved in the effect of sesamin on improving oxidative stress in hippocampus and cerebral cortex of spontaneously hypertensive rats.Methods : 40 SHRs were randomly divided into 5 groups of SHR model,sesamin treatment in diverse dosages[80 and 160 mg/(kg·d)]and captopril intervention[30mg/(kg·d)],and 10 Wistar-Kyoto rats(WKY)were included as negative controls.All groups were gavaged with these dosages at 17 : 00 daily for 12 weeks.The diastolic blood pressure was measured on conscious rats by using the tail-cuff method before administration and after every 2 weeks respectively.After the end of the last blood pressure measurement,rats were fasted for 12 hours,then sedated by intraperitoneal anesthesia.The whole-brains were taken out to make samples.The change of rat neurons in hippocampus and cerebral cortex were detected with Nissl's staining,the MDA,H2O2,SOD and T-AOC levels were examined in the homogenate of hippocampus and cerebral cortex with MTT method.NO content was examined in the homogenate of hippocampus and cerebral cortex with nitrate reductase method.The expression of n NOS positive cells in hippocampus and cerebral cortex were observed by immunohistochemical.The expression of n NOS,p22 phox and p47 phox protein in hippocampus and cerebral cortex was examined by Western blotting.Results :(1)(1)Compared with WKY group,DBP of SHR group were significantly increased(P<0.05 or P<0.01).(2)Compared with the SHR group,sesamin groups and captopril group DBP decreased significantly with prolonged administration(P<0.05 or P<0.01),sesamin groups stabilized after 10 weeks.(2)(1)Compared with WKY group,Nissl's staining shows neuronal injury in hippocampus,compared with SHR group,the administration of Ses reduced the injury in hippocampus.(2)Compared with WKY group,Nissl's staining shows neuronal injury in cerebral cortex,compared with SHR group,the administration of Ses reduced the injury in cerebral cortex.(3)(1)Compared with WKY group,the hippocampal T-AOC activity was reduced in SHR group(P<0.05 or P<0.01).Compared with SHR group,the hippocampal T-AOC activity increased by different degrees in ses[160 mg/(kg·d)]and captopril group(P<0.05 or P<0.01).(2)Compared with WKY group,the T-AOC activity in cerebral cortex was reduced in SHR group(P<0.05 or P<0.01).Compared with SHR group,the T-AOC activity in cerebral cortex increased by different degrees in ses[160mg/(kg·d)],ses[80 mg/(kg·d)]and captopril group(P<0.05 or P<0.01).(3)Compared with WKY group,the hippocampal H2O2 level increased in SHR group(P<0.05).Compared with SHR group,it reduced in ses[160 mg/(kg·d)]and captopril group(P<0.05 or P<0.01).(4)Compared with WKY group,the H2O2 level in cerebral cortex increased in SHR group(P<0.05).Compared with SHR group,it reduced in ses[160 mg/(kg·d)]and captopril group(P<0.05 or P<0.01).(4)(1)Compared with WKY group,the hippocampal SOD level was reduced in SHR group(P<0.05).Compared with SHR group,the hippocampal SOD level increased by different degrees in ses[160 mg/(kg·d)],ses[80 mg/(kg·d)]and captopril group(P<0.05 or P<0.01).(2)Compared with WKY group,the SOD level in cerebral cortex was reduced significantly in SHR group(P<0.01).Compared with SHR group,the SOD level in cerebral cortex increased by different degrees in ses[160 mg/(kg·d)],ses[80mg/(kg·d)]and captopril group by afferent degrees(P<0.05 or P<0.01).(3)Compared with WKY group,the hippocampal MDA level increased in SHR group(P<0.05).Compared with SHR group,it reduced in ses[160 mg/(kg·d)]and captopril group(P<0.05 or P<0.01).(4)Compared with WKY group,the MDA level in cerebral cortex increased significantly in SHR group(P<0.01).Compared with SHR group,it reduced in ses[160 mg/(kg·d)],ses[80 mg/(kg·d)]and captopril group by different degrees(P<0.05 or P<0.01).(5)(1)Compared with WKY group,the hippocampal NO content was increased in SHR group(P<0.05).Compared with SHR group,the content decreased by different degrees in ses[160 mg/(kg·d)]and captopril group(P<0.05 or P<0.01).(2)Compared with WKY group,the NO content in cerebral cortex was increased in SHR group(P<0.05).Compared with SHR group,the NO content in cerebral cortex decreased in ses[160 mg/(kg·d)]and captopril group by different degrees(P<0.05 or P<0.01).(6)(1)Compared with WKY group,neuronal nitric oxide synthase(n NOS)positive cells expressing significantly increased in the different hippocampal regions of SHR,AIOD value significantly increased(P<0.01).Compared with SHR group,neuronal nitric oxide synthase(n NOS)positive cells expressing significantly decreased in different administration groups by different degrees(P<0.05 or P<0.01).Especially in DG region,AIOD value decreased(P<0.01 ? P<0.05)Compared with SHR group,neuronal nitric oxide synthase(n NOS)positive cells expressing decreased in ses[160 mg/(kg·d)]and captopril group by different degrees in CA1,CA2 and CA3 regions(P<0.05 ? P<0.01),AIOD value decreased(P<0.01 ? P<0.05).(2)Compared with WKY group,neuronal nitric oxide synthase(n NOS)positive cells expressing significantly increased in cerebral cortex,AIOD value increased significantly(P<0.01),Compared with SHR group,neuronal nitric oxide synthase(n NOS)positive cells expressing significantly decreased in ses[160 mg/(kg·d)]and captopril group(P<0.01),AIOD value decreased significantly(P<0.01).(7)(1)Compared with WKY group,the hippocampal neuronal nitric oxide synthase(n NOS)protein expression was increased in SHR group(P<0.01).Compared with SHR group,the expression decreased significantly in ses[160 mg/(kg·d)]and captopril group(P<0.01).(2)Compared with WKY group,the NO content in cerebral cortex was increased in SHR group(P<0.01).Compared with SHR group,the neuronal nitric oxide synthase(n NOS)protein expression in cerebral cortex decreased significantly in ses[160 mg/(kg·d)]and captopril group(P<0.01).(8)(1)Compared with WKY group,the hippocampal p47 phox protein expression has increased in SHR group significantly(P<0.01).Compared with SHR group,the expression decreased significantly in ses[160 mg/(kg·d)]and captopril group(P<0.01).(2)Compared with WKY group,the p47 phox protein expression in cerebral cortex was significantly increased in SHR group(P<0.01).Compared with SHR group,the p47 phox protein expression in cerebral cortex decreased in ses[160 mg/(kg·d)]and captopril group by different degrees(P<0.05 or P<0.01).(3)Compared with WKY group,the hippocampal p22 phox protein expression was increased in SHR group significantly(P<0.01).Compared with SHR group,the expression decreased by different degrees in ses[160 mg/(kg·d)],ses[80 mg/(kg·d)]and captopril group(P<0.01).(4)Compared with WKY group,the p22 phox protein expression in cerebral cortex was increased in SHR group significantly(P<0.01).Compared with SHR group,the expression decreased significantly in different administration group(P<0.01).Conclusions :(1)Sesamin could effectively reduce SHR blood pressure and improve the pathological injury in hippocampus and cerebral cortex of SHR.(2)The mechanism may be sesamin could improve oxidative stress in hippocampus and cerebral cortex of spontaneously hypertensive rats by reducing H2O2 level,increasing T-AOC activity and SOD level;reducing MDA level and NO content in hippocampus and cerebral cortex of spontaneously hypertensive rats;down regulating of n NOS,p22 phox and p47 phox protein expression and inhibiting these oxidative-stress-inducing factors mentioned above.