Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

Aim To observe the effect of lipopolysac-charide(LPS)induced supernatant of BV-2 cells on the inflammatory response and apoptosis of HT22 neu-rons.Methods After the concentration and time of LPS were determined by CCK-8 method,BV-2 cells were cultured with medium without LPS and medium containing LPS,the morphological changes of BV-2 microglia were observed by inverted microscope,and the CD86/CD206 ratio of BV-2 microglia was detected by immunofluorescence.Subsequently,BV-2 cell cul-ture supernatants were isolated and added to HT22 neuronal culture to observe the effect on the inflamma-tory response of HT22 neurons.The proliferation of HT22 neurons was detected by CCK-8 method and EdU method.The structural changes of HT22 neurons were observed under the microscope and examined by urani-um-lead staining.The levels of cytokines interleukin-1β(IL-1β),interleukin-10(IL-10),nuclear factor kappa-B(NF-κB)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent as-say(Elisa).Neuronal apoptosis was detected by the TUNEL method.The protein expressions of Bax,Bcl-2 and inflammatory factors were detected by Western blot.Results After induction with 1 mg·L-1 LPS,BV-2 cells exhibited increased cell body size,thicker protrusions on both side,and some cells showed de-formed protrusions,the CD86/CD206 ratio in BV-2 cells decreased,promoting the transformation of BV-2 cells from M2 type to M1 type.After treating with the culture supernatant of BV-2 cells,HT22 neuronal cell activity and proliferation were reduced,axons short-ened,and the number of cells decreased.Neuronal cell bodies were enlarged and some cells were de-formed,with damaged cell membranes,round cell nu-clei but displaced nucleoli from the normal position,swollen mitochondria with vacuoles,reduced internal ridge structures,and increased levels of inflammatory factors NF-κB,IL-1 β,and TNF-α(P＜0.05 or P＜0.01),while the anti-inflammatory factor IL-10 de-creased(P＜0.05),protein expression of the pro-apoptotic indicator Bax increased(P＜0.01),and the protein expression of the anti-apoptotic indicator Bcl-2 decreased(P＜0.05).Conclusion After induction of BV-2 cell polarization by LPS,the supernatant could inhibit HT22 neuronal cell viability,upregulate inflam-matory factor expression and promote apoptosis.

Aim To infer novel therapeutic and phar-macological targets related to lung cancer treatment through multiomics approaches,so as to provide new directions for developing more personalized and effec-tive treatment strategies.Methods Genome-wide as-sociation study(GWAS)data analysis,pan-cancer,single-cell,transcriptomics,and protein-protein interac-tion analysis were employed in this study.Results We analyzed biomarkers and therapeutic targets associ-ated with lung cancer.The study identified key bio-markers closely related to lung cancer progression and explored the interrelationships between these biomark-ers and viral infections.According to KEGG pathway annotation,the number of genes related to metabolic processes increased significantly.In particular,metab-olites such as alanine and isoleucine emerged as pivotal factors in therapeutic interventions.The IgD+CD24+and IgD+CD24-B cell subsets were identified as cen-tral elements in immune evasion and treatment re-sponse.Concurrently,the Lachnospiraceae and Prevo-tella were shown to modulate host immune responses and the tumor microenvironment by regulating short-chain fatty acid levels,thereby opening novel avenues for cancer research.Conclusions Through mul-tiomics analysis combined with transcriptomics and pro-teomics analysis,we identify several potential therapeu-tic targets for lung cancer,providing key insights for developing novel treatment strategies.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

AIM:To investigate the types and mechanisms of lung injury induced by high-altitude exposure in mice.METHODS:Eight-week-old male C57BL/6 mice were randomly assigned to a normoxia group and a hypobaric hy-poxia exposure group,with 10 mice in each group.The hypobaric hypoxia group was continuously exposed to a hypobaric hypoxia environment simulating an altitude of 6 000 m for 3 d to establish an acute lung injury model.Lung tissues were collected.Lung pathological changes were evaluated using HE and Masson staining.Transcriptome analysis was conducted using DESeq2 and ClusterProfiler to identify differentially expressed genes and pathways,and hub genes were screened us-ing the STRING database.RESULTS:Compared with the normoxia group,the hypobaric hypoxia group exhibited signifi-cant increases in alveolar septal thickness,hyaline membrane formation,and neutrophil infiltration both in the alveolar space and the interstitial space,along with elevated lung injury scores(P<0.01),with no significant fibrosis observed.The mRNA levels of Alas2,Slc4a1,Rhag,Car1,Car2,Hbb,Agtr1b,Bmp2,Bmper,Vegfc,Foxm1,Fgf18,Igf1,Cx-cl12 and Mmp14 genes were significantly elevated(P<0.01),while Notch1,Notch4 and Cxcr4 mRNA levels were signifi-cantly decreased(P<0.01).Protein levels of inducible nitric oxide synthase(iNOS),cleaved caspase-3,cleaved PARP,fibronectin,elastin,tenascin C,tissue inhibitor of metalloproteinase-1(TIMP1),WNT3a,and β-catenin were signifi-cantly increased(P<0.05).CONCLUSION:Short-term high-altitude hypobaric hypoxia exposure induced acute lung in-jury in mice by significantly altering the expression of genes involved in apoptosis,vascular permeability regulation,extra-cellular matrix remodeling,and type Ⅱ alveolar epithelial cell proliferation.

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

AIM To investigate the effects of Liangxue Heying Formula-medicated serum(LXHY-MS)on human umbilical vein endothelial cells(HUVECs)induced by lipopolysaccharide(LPS).METHODS CCK-8,DCFH-DA fluorescence probe and Western blot method were used to screen the LPS concentration in modeling and the serum LXHY concentration for treatment.The HUVECs divided into the normal group,the model group and the LXHY-MS group had their SOD activity detected by automatic biochemical analyzer;their MDA level detected by colorimetry;their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 detected by Western blot;and their mROS expression and recruitment effect on THP-1 photographed with high connotation.With the use of JAK2/STAT3 pathway inhibitor(AG490),the HUVECs divided into the normal group,the AG490 group,the LPS group,the LPS+AG490 group,the LPS+LXHY-MS group,and LPS+LXHY-MS+AG490 group were subjected to the corresponding treatment,followed by the detection of their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 by Western blot.RESULTS Compared with the normal group,the model group displayed decreased SOD activity(P＜0.01),increased MDA level(P＜0.05),increased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),and increased mROS expression and THP-1 cells recruitment.Compared with the model group,the LXHY-MS group shared increased SOD activity(P＜0.05),decreased MDA level(P＜0.01),decreased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),reduced mROS expression and THP-1 cells recruitment.Given the use of AG490,the model group displayed increased protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 in contrast to the normal group(P＜0.05,P＜0.01);each intervened group showed decreased expressions of related proteins in contrast to the model group(P＜0.05,P＜0.01).CONCLUSION LXHY-MS may protect the injury due to the activation of HUVECs by inhibiting the JAK2/STAT3 signaling pathway.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.