[Objective]To explore the regulatory mechanism of hypoxia exposure on carbon metabolism pathway in spleen of mice.[Methods]C57BL/6 mice were raised at altitudes of 400 m and 4 200 m,with 5 mice in each group.After 30 days,spleen tissues were aseptically removed for analysis of differentially expressed genes,proteins,and metabolites using transcriptome sequencing,proteomics,and non-targeted metabolomics.GO and KEGG enrichment analysis were conducted to explore key pathways.The key genes and protein in the pathway were validated by RT-qPCR and Western blot.[Results]Transcriptome sequencing revealed a significant difference in the expression of 4 213 genes in hypoxic exposure,of which 1 947 were up-regulated and 2 266 were down-regulated.The analysis of differentially expressed proteins showed that 166 proteins were up-regulated and 39 proteins were down-regulated.The results of non-targeted metabolomics showed that 133 different metabolites were screened under high altitude hypoxia condition,of which 95 were up-regulated and 38 were down-regulated.KEGG enrichment analysis showed that differentially expressed genes,differentially expressed proteins and differentially expressed metabolites were enriched into the carbon metabolic pathway.Therefore,the key genes and proteins in the carbon metabolic pathway were verified.The mRNA and protein expressions of PGAM2、ENO3、PRPS2、PGLS、RPE、IDH3A、SUCLA2 and MDH2 were significantly down-regulated in the carbon metabolism pathway.[Conclusion]Low oxygen environment at high altitude weakens glycolysis,tricarboxylic acid cycle and pentose phosphate pathway by inhibiting the carbon metabolism pathway of the body,resulting in oxidative stress and energy metabolism imbalance.

Objective To screen and validate the key genes involved in hypoxia-induced inflammatory reactions in mice using transcrip-tome sequencing and bioinformatics. Methods C57/BL6 mice were bred at altitudes of 4200 m and 400 m,and mouse models were con-structed for the plateau hypoxia (HKT) group and the plain normoxia (PKC) group. Kidney tissues were aseptically removed after 30 days,renal pathological changes were analyzed by HE staining,blood gas analysis and renal index changes were measured in the mice under hypoxia. The kidney tissues of mice in the HKT and PKC groups were analyzed using transcriptome sequencing,key genes were screened using bioinformatics technology,and these genes were verified using real-time quantitative reverse transcription PCR (RT-qPCR) and Western blotting. Results HE staining showed glomerular atrophy in mice in the HKT group compared with the PKC group,and a decrease in blood gas analysis and renal index occurred in mice exposed to hypoxia. Transcriptome sequencing analysis revealed 3007 differentially expressed genes (DEGs) in the HKT group,of which 123 were inflammation-related DEGs (IR-DEGs). GO and KEGG enrichment analyses of IR-DEGs showed significant enrichment in inflammation-related signaling pathways,such as cytokine-cytokine receptor interactions and chemokines. The results of the protein-protein interaction (PPI) network construction of IR-DEGs showed that six hub genes,STAT3,TLR7,CD68,NFKBIA,LEP,and APOE,were identified,and the mRNA expression of these six genes was upregulated according to RT-qPCR results,which was in agreement with the results of transcriptome sequencing. Western blotting showed that CD68,NFKBIA,LEP,TLR7,and APOE expression was upregulated while STAT3 expression was downregulated. Conclusion STAT3,CD68,NFKBIA,LEP,TLR7,and APOE are the key genes involved in hypoxia-induced inflammatory reactions. A hypoxic environment induced inflammatory reactions in mouse kidney tissues by upregulating the expression of TLR7,CD68,STAT3,LEP,and APOE.

Objective To screen and validate the key genes involved in hypoxia-induced inflammatory reactions in mice using transcrip-tome sequencing and bioinformatics. Methods C57/BL6 mice were bred at altitudes of 4200 m and 400 m,and mouse models were con-structed for the plateau hypoxia (HKT) group and the plain normoxia (PKC) group. Kidney tissues were aseptically removed after 30 days,renal pathological changes were analyzed by HE staining,blood gas analysis and renal index changes were measured in the mice under hypoxia. The kidney tissues of mice in the HKT and PKC groups were analyzed using transcriptome sequencing,key genes were screened using bioinformatics technology,and these genes were verified using real-time quantitative reverse transcription PCR (RT-qPCR) and Western blotting. Results HE staining showed glomerular atrophy in mice in the HKT group compared with the PKC group,and a decrease in blood gas analysis and renal index occurred in mice exposed to hypoxia. Transcriptome sequencing analysis revealed 3007 differentially expressed genes (DEGs) in the HKT group,of which 123 were inflammation-related DEGs (IR-DEGs). GO and KEGG enrichment analyses of IR-DEGs showed significant enrichment in inflammation-related signaling pathways,such as cytokine-cytokine receptor interactions and chemokines. The results of the protein-protein interaction (PPI) network construction of IR-DEGs showed that six hub genes,STAT3,TLR7,CD68,NFKBIA,LEP,and APOE,were identified,and the mRNA expression of these six genes was upregulated according to RT-qPCR results,which was in agreement with the results of transcriptome sequencing. Western blotting showed that CD68,NFKBIA,LEP,TLR7,and APOE expression was upregulated while STAT3 expression was downregulated. Conclusion STAT3,CD68,NFKBIA,LEP,TLR7,and APOE are the key genes involved in hypoxia-induced inflammatory reactions. A hypoxic environment induced inflammatory reactions in mouse kidney tissues by upregulating the expression of TLR7,CD68,STAT3,LEP,and APOE.

Antiviral Agents/pharmacology* ; COVID-19 ; Coronavirus 3C Proteases ; Humans ; Lactams ; Leucine ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Nitriles ; Proline ; Protease Inhibitors/pharmacology* ; SARS-CoV-2

To investigate the active compounds from on the heart and brain of mice at simulated high altitude.Fifty healthy male adult BALB/c mice were randomly divided into normal control group, hypoxic model group, acetazolamide group, petroleum ether extract of (PESI) group and octacosan group with 10 mice in each group. Acetazolamide group, PESI group and octacosan group were treated with acetazolamide PESI (200 mg/kg) or octacosan by single tail vein injection, respectively. Except normal control group, the mice were exposed to a simulated high altitude of for in an animal decompression chamber. After the mice were sacrificed by cervical dislocation, the heart and brain were histologically observed by HE staining; superoxide dismutase (SOD) activity, total anti-oxidant capacity (T-AOC) and the content of malondialdehyde (MDA) in plasma, heart and brain tissues were detected by WST-1 method, ABTS method and TBA method, respectively; lactic acid and lactate dehydrogenase (LDH) activity in plasma, heart and brain tissues were detected by colorimetric method and microwell plate method, respectively; ATP content and ATPase activity in heart and brain tissues were detected by colorimetric method. PESI and octacosane significantly attenuated the pathological damages of heart and brain tissue at simulated high altitude; increased SOD activity, T-AOC and LDH activity, and decreased the contents of MDA and lactic acid in plasma, heart and brain tissues; increased the content of ATP in heart and brain tissues; increased the activities of Na-K ATPase, Mg ATPase, Ca ATPase and Ca-Mg ATPase in myocardial tissue; and increased the activities of Mg ATPase, Ca-Mg ATPase in brain tissue. PESI and octacosan exert anti-hypoxic activity by improving the antioxidant capacity, reducing the free radical levels, promoting the anaerobic fermentation, and alleviating the energy deficiency and metabolic disorders caused by hypoxia in mice.
Altitude ; Animals ; Brain/metabolism* ; Heart ; Male ; Malondialdehyde ; Mice ; Mice, Inbred BALB C ; Superoxide Dismutase/metabolism*

OBJECTIVE:To work out the quality control standard of Penqiangyan tablets.METHODS:The major herbs in the preparation were identified by TLC.The contents of total ferulic acid in Radix Angelia Sinensis and Rhizoma Chuanxiong were determined by HPLC.RESULTS:Ferulic acid had a good linearity in the range of1.244～124.4?g/ml(r=0.9984).The recovery and RSD were97.06%and1.44%(n=6)respectively.CONCLUSION:The method is simple and feasible and had a good repeatability.It can be used for the quality control of Penqiangyan tablets.

AIM: To study the influence of ginkgolides on expression of inducible nitric oxide synthase (iNOS) in rats. METHODS: Middle cerebral artery occlusion(MCAO) model was induced by ligating internal carotid artery of Sprague Dawley(SD) rats.In this model,the behavioral deficits performance of SD rats was analyzed after given ginkgolides and nimo dipin, respectively, and iNOS gene expression changes in MCAO group were investigated. RESULTS:The expression of iNOS was increased in MCAO models and inhibited in ginkgolides groups. CONCLUSION:Ginkgolides have inhibitive efficacy of iNOS on cerebral ischemia and can reduce brain damage.