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Background The exposure to diesel particulate matter (DPM) and its polycyclic aromatic hydrocarbons (PAH) is closely related to the morbidity and mortality of ischemic heart disease (IHD). However, it is unclear what key components and targets of DPM exposure involve in myocardial ischemia-hypoxia injury and associated mechanisms. Objective To identify key PAH components of DPM that act on myocardial hypoxic injury, andclarify the role of oxygen sensors-regulated anaerobic metabolism in DPM and key components-induced hypoxic injury and the targets of the key PAH components. Methods Human cardiomyocyte cell line AC16 cells were exposed to 0, 1, 5, and 10 μg·mL−1 DPM in a high glucose DMEM medium with 10% fetal bovine serum (FBS) (HGM) or low FBS (0.5%) in high glucose DMEM medium (LFM), for 12 h under 2% O2, and expression of hypoxia-inducible factor-1α (HIF-1α), Bax, and Cleaved-caspase3 was determined by Western blotting. Under normal condition, the cell viability was detected after PAH exposure for 12 h. Under the condition of ischemia-hypoxia model, cells were exposed to 0, 0.005, 0.5, and 5 µg·mL−1 PAH for 12 h, and the protein expression of HIF-1α, Bax, and Cleaved-caspase3 was determined. After exposure to DPM or PAH for 12 h, the contents of pyruvate and lactate in cells were detected. Pretreatment with glycolysis inhibitor GSK2837808A was used to explore the role of glycolysis in DPM and benzo[a]pyrene (BaP)-induced hypoxia injury. A molecular docking technique was used to analyze the binding affinity between PAH and oxygen sensors (prolyl hydroxylase domain-containing protein 2, PHD2, and factor-inhibiting hypoxia-inducible factor 1, FIH1), and the protein levels of PHD2, FIH1, and hydroxyl-HIF-1-alpha (OH-HIF-1α) after the DPM or BaP treatment were further determined. Results Under hypoxia, DPM exposure in the LFM induced the expression of HIF-1α, Bax, and Cleaved-caspase3 (P<0.01). Therefore, hypoxia and LFM were selected as the basic ischemia and hypoxia condition. Except for anthracene (Ant) (P>0.05), other PAH decreased cell viability when the concentration was above 1 μg·mL−1 (P<0.05). All concentrations of BaP induced the expression of HIF-1α protein (P<0.05), and the protein levels of Bax and Cleaved-caspase3 were up-regulated after the 0.5 and 5 µg·mL−1 BaP exposure (P<0.01). After exposure to DPM (1, 5 and 10 μg·mL−1) or BaP (0.5 and 5 μg·mL−1), the intracellular pyruvate and lactate contents increased (P<0.05). The glycolysis inhibitor co-treatment decreased the levels of HIF-1α, Bax, and Cleaved-caspase3 proteins compared with the DPM or BaP exposure group for 12 h (P＜0.05). The binding abilities of the five PAHs to the oxygen sensors PHD2 and FIH1 were strong, and BaP was the strongest. Although the DPM or BaP exposure had no effects on the protein levels of PHD2 and FIH1 in AC16 cells (P＜0.05), the protein level of OH-HIF-1α was decreased (P＜0.01). Conclusion BaP exposure can promote hypoxia and injury of myocardial cells and is the key PAH component of DPM that induces myocardial ischemia and hypoxia injury. BaP exposure inhibits the hydroxylation function of PHD2 on HIF-1α by combining with PHD2, decreases the level of OH-HIF-1α and induces HIF-1α accumulation. And then HIF-1α promotes anaerobic metabolism and accelerates ischemia and hypoxia injury of myocardial cells.
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BACKGROUND: Traditional Chinese medicine has certain value and significance in the treatment of ischemic cardiovascular and cerebrovascular diseases by regulating the ischemia-hypoxia microenvironment and improving the survival rate and differentiation rate of stem cells. OBJECTIVE: To sort out and analyze the research progress of traditional Chinese medicine on regulating ischemia-hypoxia microenvironment intervention on proliferation, differentiation, aging and autophagy of bone marrow mesenchymal stem cells in recent years. METHODS: The full-text database of Chinese journals, PubMed and Wanfang were retrieved with the keywords of “bone mesenchymal stem cells, ischemia-hypoxia microenvironment, proliferation, differentiation, aging” in English or “bone marrow mesenchymal stem cells, ischemia and hypoxia, proliferation, differentiation, aging” in Chinese for articles regarding effects of ischemia and hypoxia microenvironment on survival rate and differentiation rate of bone marrow mesenchymal stem cells published from 2002 to 2019. Fifty-five articles were selected for review, including 22 Chinese articles and 33 English articles. RESULTS AND CONCLUSION: The ischemia-hypoxia microenvironment is the important reason for the low survival rate and differentiation rate of bone marrow mesenchymal stem cells. There are many adverse reactions in the intervention of bone marrow mesenchymal stem cells with gene modification or cell molecules and drugs, which have become difficult problems to be solved in modern medicine. Exploring the internal relationship between microenvironment and stem cells using single or active components of traditional Chinese medicine combined with RNA transcriptomics is a new way to improve the viability of stem cells.
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Myocardial ischemia/hypoxia often results in damaging the structure and function of heart. Baicalein, a widely distributed flavonoid, has been shown to play an important role in the cardioprotection of ischemia/hypoxia in recent years. The cardioprotection of baicalein was mediated by regulating the cell signaling pathways and controlling the phosphorylation of key signaling molecules. These signaling pathways involved in phosphatidylinositol-3-kinase-serine/threonine kinase (PI3K/Akt), mitogen-activated protein kinase (MAPKs), and nuclear factor-κB (NF-κB), and their down signaling proteins HMGB1, MMP-2/-9, and eNOS, and apoptosis proteins as well. The interaction mechanism of baicalein on signaling pathway in myocardial ischemia/hypoxia has been reviewed.
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Objective To study the impact of Xingnaojing (XNJ) injection (a preparation of Chinese herb medicine) on the permeability of blood-brain barrier and Caveolin-1 in cortex of brain after global ischemia-reperfusion.Methods Modified Pulsinelli method for four-vessel occlusion was employed to establish the global ischemia reperfusion model in rats.Male Wistar rats were randomly (random number) divided into three groups,namely sham group,model group and XNJ group.Each group was observed at 24 h,48 h and 72 h after ischemia reperfusion.The water content of brain tissue was determined by dry/wet weight ratio,while the Evans blue (EB) concentration in brain tissue was detected by spectrophotometer.Western blot was used to detect caveolin-1 level in the cerebral cortex.Results The water contents of brain tissue in model group and XNJ group were significantly higher than that in sham group 24 hour after ischemia-reperfusion (P ＜ 0.05).But at 48 h and 72 h after ischemia-reperfusion,the brain water content in model group was significantly higher than that in XNJ group and sham group (P ＜ 0.05).The EB concentrations in brain tissue in model group and XNJ group were higher than that in sham group 24 h after ischemia-reperfusion (P ＜ 0.05).EB levels in sham group and XNJ group were significantly lower than that in model group 48 h and 72 h after ischemia-reperfusion (P ＜ 0.05).Caveolin-1 levels in cerebral cortex in sham group and XNJ group were significantly higher than that in model group 24 h,48 h and 72 h after ischemia-reperfusion (P ＜ 0.05).Conclusions After global ischemia-reperfusion,Xingnaojing (XNJ) injection could protect blood-brain barrier in virtue of regulating caveolin-1 protein level.
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Objective To study the expression and significance of vascular endothelial growth factor(VEGF) in serum of umbilical blood from the newborns of women with severe pre-eclampsia.Methods Radioimmunoassay was used to measure the serum VEGF of umbilical blood from 26 newborns of women with severe pre-eclampsia (severe pre-eclmpsia group) and 30 newborns of normal pregnancy women (control group). According to birth weight-gestational age relation,severe pre-eclampsia group included 15 newborns small for gestational age (SGA group) and 11 newborns appropriate for gestational age (AGA group).Results (1)The VEGF level of umbilical vein blood and umbilical artery blood in severe pre-eclmpsia group was significantly higher than that in control group respectively(t = 2.16, P < 0.05;t = 4.82, P < 0.01). (2) In control group and severe pre-eclampsia group, the VEGF level in umbilical artery blood was significantly higher than that in umbilical vein blood (control group: t = 2.24, P < 0.05;severe pre-eclampsia group: t = 3.00, P < 0.01). (3)In both control group and severe pre-eclampsia group, there was no significant correlation respectively between VEGF levels in umbilical vein blood or umbilical artery blood and newborns' gestational age or birth weight. (4)VEGF level of umbilical artery blood in SGA group was significantly higher than that in AGA group as well as in control group(t = 3.22, P < 0.01 ;t = 6.80, P < 0.01). Conclusions The serum VEGF level of umbilical vein blood and umbilical artery blood from the newborns of women with severe pre-eclampsia was significantly higher than that of normal pregnancy women respectively. The VEGF level of umbilical artery blood can reflect the severity degree of the damage of hypertensive disorder complicating pregnancy to their newborns to some degree.
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@#Brain ischemia/hypoxia preconditioning(I/HPC) is one kind of endocardial protective phenomenon by organism against blood and oxygen deficit.Researches discovered various proteins such as hypoxic inducible factor-1(HIF-1),heat shock proteins(HSPs),erythropoietin(EPO),Bcl-2 family,calcitoningene related peptide(CGRP) and so on participated in brain I/HPC.This essay explains function and participating I/HPC mechanism of these proteins.
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@#Brain ischemia/hypoxia preconditioning(I/HPC) is one kind of endocardial protective phenomenon by organism against blood and oxygen deficit.Researches discovered various proteins such as hypoxic inducible factor-1(HIF-1),heat shock proteins(HSPs),erythropoietin(EPO),Bcl-2 family,calcitoningene related peptide(CGRP) and so on participated in brain I/HPC.This essay explains function and participating I/HPC mechanism of these proteins.
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Objective To explore the expression pattern and effects of hypoxia inducible factor-1? (HIF-1?) in experimental spinal cord injury. Methods The expression of HIF-1? at various time was detected at levels of mRNA and protein by using methods of reverse transcription-polymerase chain reaction (RT-PCR),in situ hybridization (ISH) and immunohistochemistry. Results HIF-1? expressed more significantly at levels of mRNA and protein in all kinds of cells in the injured spinal cord than in the normal spinal cord (P