Research On Effects And Mechansims Of Astragalus On Hippocampus And Pancreas Injury In Rats Induced By Intermittent Hypoxic

Objective: In this study，we established a rat intermittent hypoxia model tosimulate similar environment of OSAHS patient. We aim to explore effects ofastragalus against intermittent hypoxia-induced rats hippocampal neurons and isletβ-cell apoptosis and its concrete mechanisms. Furthermore we can seek a interventiontarget, which can provide a theoretical basis for prevention and treatment of thenervous system damage and glucose metabolism disorders that induced by OSAHS.Methods: Forty-eight male matule wistar rats were randomly divided into fourgroups：The normal control group,intermittent normoxia group,intermittent hypoxiagroup and astragalus intervention group. Plexiglass cabin was applied to establish ratintermittent hypoxia model.Cultured animals were exposed to intermittent hypoxia，throughout the eight hours of light time（8:00am–4:00pm). Intermittent hypoxiaprofiles consisted of alternating normoxia (21%O2) and hypoxia (5%O2) every90seconds. Treating intermittent hypoxia rats with astragalus injection as Astragalusintervention group. TUNEL was used to assay rat hippocampal nerve cells and isletβ-cell apoptosis rate; Reversed Transcription-PCR,immunohistochemistry andWestern blotting were applied to detect apoptosis-associated genes and proteinsexpression in each group.Results:1.The effects of Astragalus extract against intermittent hypoxia-induced hippocampal neurons apoptosis in rats and its possiblemechanisms:1)Applying TUNEL for hippocampal neurons apoptosis, wedemonstrated that the level of apoptosis rate in intermittent hypoxia group wassignificantly higher than that in intermittent normoxia group, while in astragalusgroup it was significantly lower than that in intermittent hypoxia group.2)UsingReversed Transcription-PCR,immunohistochemistry and Western blotting to examineHIF-1α and iNOSmRNA and its protein expression, we shows that compared withintermittent normoxic group, HIF-1α and iNOSmRNA and its protein expression wereobviously higher in intermittent hypoxia group, while in astragalus group, thoseexpression were less than that in intermittent hypoxia group significantly.2.Theeffects of Astragalus extract against intermittent hypoxia-induced islet β-cell apoptosis in rats and its possible mechanisms:1) Applying TUNEL for islet β cellsapoptosis we demonstrated that the apoptosis rate in intermittent hypoxia group wassignificantly higher than that in intermittent normoxia group, while in astragalusgroup it was significantly less than that in intermittent hypoxia group.2) Usingimmunohistochemistry and Western blotting to examine Bcl-2and Bax proteinexpression, we shows that compared with intermittent normoxic group, Bcl-2proteinexpression were obviously lower in intermittent hypoxia group, while Bax proteinexpression were obviously higher in intermittent hypoxia group.Howere in astragalusgroup, Bcl-2protein expression were obviously higher than that in intermittenthypoxia group, while Bax protein expression were obviously lower than that inintermittent hypoxia group.Conclusion:1.OSAHS-induced intermittent hypoxia will cause hippocampalneurons and pancreatic β cells apoptosis.2. Astragalus decrease intermittenthypoxia-induced hippocampal neurons and pancreatic β cells apoptosis throughintervene HIF-1α,iNOS,Bcl-2,Bax protein expression.3. Astragalus play a protectiverole in the intermittent hypoxia-induced nervous system damage and glucosemetabolism disorders.