Objective To investigate the protective effect and molecular mechanism of bloodletting acupuncture at Jing-well points on acute high-altitude hypoxia brain injury through regulating PI3K/AKT/mTOR signaling pathway-mediated mitochondrial autophagy,and to provide an effective target and theoretical basis for the clinical use of bloodletting acupuncture at Jing-well points to prevent and treat acute high-altitude hypoxia brain injury.Methods Male SD rats were randomly divided into Control group(n=15)and experimental group,and the experimental group was divided into Model group(n=15),Bloodletting Acupuncture at Jing-well Points of hand group(BAJP group,n=15),Bloodletting Acupuncture at Non-Acupoint group(BANA group,n=15).The low pressure oxygen chamber was depressurized to 6000 m altitude,and the rats in each experimental group were treated with low-pressure hypoxia for 72 h to replicate the acute high-altitude hypoxia brain injury rat model.The rats in the BAJP group were bled according to the order of"Shaoshang"(LU11),"Shangyang"(LI1),"Zhongchong"(PC9),"Guanchong"(SJ1),"Shaochong"(HT9),"Shaoze"(SI1),once a day for 7 days.The rats in the BANA group were bled by cutting the tail tip daily,and the amount of blood bled was 15-20 μL in both groups.The expression levels of PI3K,AKT and mTOR in hippocampal tissues of rats were detected by Western blot;AKT and mTOR mRNA expression levels in hippocampal tissues of rats were detected by PCR.Results Compared with the Control group,the number of degenerative necrotic vertebral cells in CA1 area of hippocampal tissue,swelling of mitochondria,appearance of autophagosomes,and increase of apoptosis in hippocampal tissue of Acute High-altitude Hypoxia(AHH)rats were significantly increased;After bloodletting acupuncture at Jing-well points of hand treatment,various brain injury manifestations in AHH rats were alleviated;Bloodletting acupuncture at non-acupoint had no significant ameliorating effect on AHH rats′ brain injury.Western blot detected a significant decrease in the phosphorylation levels of PI3K,AKT,and mTOR in the hippocampal tissues of AHH rats compared to Control group rats(P<0.01),and the phosphorylation levels of the three molecules were further decreased after bloodletting acupuncture at Jing-well points of hand treatment(P<0.01),and bloodletting acupuncture at non-acupoint treatment did not have significantly affect on the phosphorylation levels of these molecules(P>0.05),and AKT,mTOR mRNA expression levels further demonstrated the above trend.Conclusion Bloodletting acupuncture at Jing-well points of hand can play a protective role against acute high-altitude hypoxia brain injury with points specificity,and the mechanism may be related to the inhibition of PI3K/AKT/mTOR pathway to promote the elevated level of mitochondrial autophagy,improve mitochondrial physiology,and enhance the body′s ability to resist apoptosis and hypoxia.