加减补阳还五汤对慢性间歇性低氧脑损伤的神经保护机制OA

Objective:To explore the protective mechanism of Modified Buyang Huanwu Decoction against brain injury induced by chronic intermittent hypoxia(CIH)through the protein kinase B1(Akt1),mitogen-activated protein kinase 3(MAPK3),and Wnt/β-catenin(CTNNB1)signaling pathways.Methods:Thirty male Sprague-Dawley(SD)rats were randomly divided into three groups:a normoxic control group,a model group,and a traditional Chinese medicine(TCM)group,with 10 rats in each group.The normoxic control group didn't receive any intervention.The model and TCM groups were subjucted to chronic intermittent hypoxia for 8 hours per day.The TCM group was orally administered Modified Buyang Huanwu Decoction(13.86 g/kg)twice daily,30 minutes before and after daily hypoxia exposure,for 18 consecutive weeks.The total number of arm entries and spontaneous alternation rate were evaluated using the Y-maze test.Brain tissue morphology was examined through hematoxylin-eosin(HE)staining.The ultrastructure of mitochondria in brain cells was inspected by transmission electron microscopy(TEM).Hippocampal cell apoptosis was detected by TUNEL staining.Serum levels of malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),and inter-leukin-6(IL-6)were measured using enzyme-linked immunosorbent assay(ELISA).Protein expression levels of Akt1,MAPK3,CTN-NB1,and Caspase-3 were detected by Western blot analysis.Results:Compared with the normoxic control group,rats in the model group exhibited a decreased spontaneous alternation rate(P<0.05).Histologically,these rats had disordered cellular arrangement in the brain tissue,accompanied by obvious inflammatory cell infiltration and nuclear pyknosis.Ultrastructurally,the brain mitochondria of these rats exhibited swelling,disrupted cristae,and vacuolar degeneration.Additionally,the number of TUNEL-positive cells in the brain tissue of these rats increased significantly,and the serum levels of TNF-α,MDA,and IL-6 were significantly elevated(P<0.05),while the SOD activity decreased significantly(P<0.05).Moreover,the protein expression levels of Akt1 and CTNNB1 were signifi-cantly downregulated(P<0.05),and the Caspase-3 protein expression was significantly upregulated(P<0.05).Compared with the model group,rats in the TCM group exhibited a significant increase in the spontaneous alternation rate(P<0.05).Their brain tissue had significantly improved cellular arrangement,with no obvious inflammatory cell infiltration.The brain mitochondria of these rats presented a normal morphology,with clear and intact cristae and no obvious vacuolar degeneration.Meanwhile,the number of TUNEL-positive cells in the brain tissue was significantly reduced,the serum levels of TNF-α,MDA,and IL-6 were significantly decreased(P<0.05),and the SOD activity significantly increased(P<0.05).The protein expression of Caspase-3 was significantly downregulated(P<0.05),whereas the expression of Akt1,MAPK3,and CTNNB1 was significantly upregulated(P<0.05).Conclu-sion:The Modified Buyang Huanwu Decoction can inhibit oxidative stress and inflammatory responses,thereby ameliorating CIH-induced brain injury in rats.The underlying mechanism might be associated with increased protein expression of Akt1,MAPK3,and CTNNB1,along with decreased protein expression of Caspase-3,in the hippocampal tissue.