| ObjectiveTo explore and analyze the protective effect and mechanism ofα-mangostin on cerebral ischemia-reperfusion injury in rats.MethodsAfter the middle cerebral artery occlusion(MCAO)models of rats have been established,SD rats were randomly divided into 5 groups according to weights,including the sham operated group,the model group(I/R group),low,medium and high dose treatment of α-mangost group(α-M-L,α-M-M,α-M-H group).After 14 days of routine feeding,the neurobehavioral scores of rats in each group were measured.Then the rats were killed by decollation and their brain tissues were taken.After brain stem and cerebellum were removed,the area of cerebral infarction was measured by 2,3,5-triphenyl tetrazolium chloride(TTC)staining and the moisture content of brain tissue was measured by dry weighing method.The cell morphology of cerebral ischemia area was observed under optical microscope.Under fluorescence microscope,the survival neurons in the ischemic area of each group were observed.The content of superoxide dismutase(SOD)and malondialdehyde(MDA)in rats’ brain tissue were detected by the assay kit.Enzyme Linked Immuno Sorbent Assay(ELISA)was used to detect the content of inflammatory factors and Western blot was used to detect the expression of protein related to NF-κB signal pathway and apoptosis in brain tissue of rats in each group.Results(1)The model group had the highest neurobehavioral score(P<0.05).Theneurobehavioral score of high dose group was significantly lower than that of medium dose group and low dose group(P<0.05).(2)The volume of cerebral infarction in the low,middle and high dose group was significantly smaller than that in the model group(P<0.05),and the volume of cerebral infarction in high dose group was also significantly smaller than that in low dose group and middle dose group(P<0.05).(3)Compared with the sham group,the water content of brain tissue in other groups was significantly higher(P<0.05).The water content of brain tissue in high dose group was significantly lower than that in low and medium dose groups(P<0.05).(4)Under the light microscope,the morphology of the cells in the ischemic area of the brain tissue in model group changed obviously,the volume of the cells narrowed obviously,and the nuclear pyknosis was significant.Compared with the model group,the cellular edematous state of the brain ischemia area in the low,medium and high dose groups of α-mangostin was improved.In the high-dose α-mangostin group,the degree of cell swelling was most obviously relieved,and the cell morphology was basically normal.(5)The number of surviving neurons in the model group was the least and significantly less than that in the sham operation group and each α-mangostin treatment group(P<0.05).The number of surviving neurons in high dose group was significantly higher than that in low and medium dose groups(P<0.05).(6)The SOD activity of the model group was significantly lower than that of each α-mangostin treatment group(P<0.05).The MDA content of the model group was significantly higher than that of eachα-mangostin treatment group(P<0.05).(7)Compared with the model group,the levels of IL-1β,IL-6,TNF-α and other inflammatory factors in the low-,medium-,and high-dose α-mangostin groups were significantly reduced(P<0.05).The levels of IL-1β and IL-6 in the high-dose α-mangostin group were significantly lower than those in the low-and medium-dose α-mandolin groups(P<0.05).(8)Compared with the model group,the expression levels of the three NF-κB signaling pathway-related proteins p-NF-κB,Cyclin D1 and c-Myc in the low-,medium-,and high-dose α-mangostin groups were significantly reduced(P<0.05).The expression of Cyclin D1 and c-Myc protein in the high-doseα-mangostin group was significantly lower than that in the low-and medium-dose groups(P<0.05).(9)Compared with the model group,the expression levels of the three apoptosis-related proteins Bax,Cleared caspase-3 and Cleaned caspase-9 in the brain tissues of rats in each group were reduced significantly(P<0.05),while the expression levels of Bcl-2 were increased significantly(P<0.05).Conclusionsα-Mangostin can lessen cerebral infarction area by anti-oxidation,reducing inflammation after brain tissue reperfusion injury,inhibiting the activation of NF-κB signaling pathway,and inhibiting mediated apoptosis through mitochondrial apoptosis signaling pathway,which has a protective effect on cerebral ischemia-reperfusion injury in rats. |
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