Effect Of Tibetan Medicine Siwei Huangqi Powder On Autophagy Of Rat Hippocampal Neurons Induced By Hypobaric Hypoxia

Objective To explore the effect of Tibetan medicine Siwei Huangqi Powder on autophagy of rat hippocampal neurons induced by hypobaric hypoxia.Methods A total of 72 male Sprague Dawley rats were randomly divided into normoxic control group(NC,n=24),hypoxic control group(HC,n=24)and hypoxic drug group(HD,n=24),then every group was subdivided into 3,7,15 and 30 d group with 6 rats per each group according to different time points.HC and HD rats were put in a hypobaric chamber where rats were simulated altitude of 5 000 meters for hypobaric hypoxia environment.HD,HC and NC rats were treated with 1mL Tibetan medicine Siwei Huangqi power aqueous extract and 1mL 0.9% normal saline,respectively.Elisa was used to detect serum HIF-1? levels.Transmission electron microscopy was used to observe autophagosomes in each group.Expression level and intracellular localization of LC3 were observed under confocal microscopy.The pathological morphological changes of hippocampal neurons was observed by Nissl staining method.The expression levels of autophagy-related protein(LC3?/?,p62)and neuron-related protein(PKC?,BDNF)were assessed by western blot.Results 1.Compared with the normoxic control group,the hypoxic control group,at 3 d and 7 d,the HIF-1? level in the serum increased(p<0.05);the hippocampal neuronal damage degree aggravated,the PKC? and BDNF protein levels decreased(p<0.05);the number of autophagosomes in hippocampal nrurons increased,and the LC3?/? protein level increased(p<0.05),the p62 protein level decreased(p<0.05);at 15 d and 30 d,there was no significant change in serum HIF-1? level(p>0.05);the hippocampal neuronal damage degree aggravated,the PKC? and BDNF protein levels increased(p<0.05);at 15 d,in hippocampal nrurons,the LC3II/I protein level decreased(p<0.05),the p62 protein level increased(p<0.05);at 30 d,the LC3II/I and p62 protein levels were not significantly changed in hippocampal nrurons(p>0.05).2.After intervention with Tibetan medicine Siwei Huangqi Powder,compared with the hypoxic control group,the hypoxic drug group,at 3 d and 7 d,the HIF-1? level in the serum decreased(p<0.05);the hippocampal neuronal damage degree alleviated,and the PKC? and BDNF protein levels increased(p<0.05);the number of autophagosomes in hippocampal nrurons decreased,the LC3?/? protein level decreased(p<0.05),the p62 protein level increased(p<0.05);at 15 d and 30 d,there was no significant change in serum HIF-1? level(p>0.05);the hippocampal neuronal damage degree alleviated,the PKC? protein level decreased(p<0.05),and the BDNF protein level increased(p<0.05);at 15 d,in hippocampal nrurons,the LC3II/I protein level increased(p<0.05),the p62 protein level decreased;at 30 d,there was no significant change in the protein levels of LC3II/I and p62(p>0.05).3.PKC? positively correlated with BDNF protein level change in the hypoxic control group(r= 0.976,p<0.01);PKC? and BDNF negatively correlated with LC3?/? protein level change in the hypoxic control and the hypoxic drug group in the third and seventh days(r=-0.981,p<0.05;r=-0.899,p<0.05,n=6).Conclusion 1.In the acute hypoxic phase,hypobaric hypoxia can promote the formation of autophagosomes and overexpression of autophagy proteins,inhibit PKC? and BDNF protein levels,and damage hippocampal neurons.2.Tibetan medicine Siwei Huangqi Powder can decrease the autophagy activity,up-regulate PKC?,BDNF protein levels,and alleviate hippocampal neuronal damage.