Acute myocardial ischaemia is a common acute .disease and a common cause of sudden death.However, it is difficult to diagnose in patients who died within 6 hours after the onset of myocardial ischaemia. The occurrence...Acute myocardial ischaemia is a common acute .disease and a common cause of sudden death.However, it is difficult to diagnose in patients who died within 6 hours after the onset of myocardial ischaemia. The occurrence of sudden cardiac death often has pathological basis of primary heart diseases, which may lead to a series of changes in metabolism and gene expression.1 Recent research found that hypoxia inducible factor 1 alpha （HIF-1α） is a sensitive marker of hypoxia; its gene expression is upregulated within several minutes after acute myocardial ischaemia, followed by the upregulation of its protein and its expression will remain high if the inducement continues. Its expression in nonhypoxic cardiac muscle is very low. This characteristic may be used to differentiate hypoxic factors from nonhypoxic factors, and help to judge the cause of death. This study explored the expression of HIF-1α in hypoxic cardiac muscle by establishing an acute myocardial ischaemia model in mice, and observed its dynamic changes to provide reference for analysing causes of death within 48 hours after death.展开更多
This study used a novel combination of in vivo and in vitro experiments to show that Braintone had neuroprotective effects and clarified the molecular mechanisms underlying its efficacy. The Chinese herbal extract Bra...This study used a novel combination of in vivo and in vitro experiments to show that Braintone had neuroprotective effects and clarified the molecular mechanisms underlying its efficacy. The Chinese herbal extract Braintone is composed of Radix Rhodiolase Essence, Radix Notoginseng Essence, Fofium Ginkgo Essence and Rhizoma Chuanxiong. In vivo experiments showed that cerebral infarction volume was reduced, hemispheric water content decreased, and neurological deficits were alleviated in a rat model of permanent middle cerebral artery occlusion after administration of 87.5, 175 or 350 mg/kg Braintone for 7 consecutive days. Western blot analysis showed that Braintone enhanced the expression of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothe- lial growth factor in the ischemic cortex of these rats. The 350 mg/kg dose of Braintone produced the most dramatic effects. For the in vitro experiments, prior to oxygen-glucose deprivation, rats were intragastrically injected with 440, 880 or 1 760 mg/kg Braintone to prepare a Braintone-co ntaining serum, which was used to pre-treat human umbilical vein endothelial cells for 24 hours. Human umbilical vein endothelial cell injury was alleviated with this pre-treatment. Western blot and real-time PCR analysis showed that the Braintone-containing serum increased the levels of hy- poxia-inducible factor la mRNA and protein, heine oxygenase-1 protein and vascular endothelial growth factor mRNA in oxygen-glucose deprived human umbilical vein endothelial cells. The 1 760 mg/kg dose produced the greatest increases in expression. Collectively, these experimental findings suggest that Braintone has neuroprotective effects on ischemia-induced brain damage via the up-regulation of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothelial growth factor expression in vascular endothelial cells.展开更多
Background:Exercise induces blood flow redistribution among tissues,leading to splanchnic hypoperfusion.Intestinal epithelial cells are positioned between the anaerobic lumen and the highly metabolic lamina propria wi...Background:Exercise induces blood flow redistribution among tissues,leading to splanchnic hypoperfusion.Intestinal epithelial cells are positioned between the anaerobic lumen and the highly metabolic lamina propria with an oxygen gradient.Hypoxia-inducible factor(HIF)-la is pivotal in the transcriptional response to the oxygen flux.Methods:In this study,the pimonidazole hydrochloride staining was applied to observe the tissue hypoxia in different organs,which might be affected by the blood flow redistribution.The HIF-la luciferase reporter ROSA26 oxygen-dependent degradation domain(ODD)-Luc/^+mouse model(ODD domain-Luc;female,n=3-6/group) was used to detect the HIF-la expression in the intestine.We used 3 swimming models:moderate exercise for 30 min,heavy-intensity exercise bearing 5% bodyweight for 1.5 h,and long-time exercise for 3 h.Results:We found that 1 session of swimming at different intensities could induce tissue hypoxia redistribution in the small intestine,colon,liver and kidney,but not in the spleen,heart,and skeletal muscle.Our data showed that exercise exacerbated the extent of physiological hypoxia in the small intestine.Next,using ODD-Luc mice,we found that moderate exercise increased the in vivo HIF-1α level in the small intestine.The postexercise HIF-1α level was gradually decreased in a time-dependent manner.Interestingly,the redistribution of tissue hypoxia and the increase of HIF-la expression were not related to the exercise intensity and duration.Conclusion:This study provided evidence that the small intestine is the primary target organ for exercise-induced tissue hypoxia and HIF-la redistribution,suggesting that HIF-1α may be a potential target for the regulation of gastrointestinal functions after exercise.展开更多
Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/ reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxi- dative stress. By contr...Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/ reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxi- dative stress. By contrast, normobaric oxygen has the rapid and non-invasive characteristics and may have therapeutic effects on ischemic/hypoxic disease. Rats inhaled normobaric oxygen （95% 02） for 6 consecutive days, and then a rat model of focal cerebral ischemia was established. Nisst and 2,3,5-triphenyltetrazolium chloride （TTC） staining revealed that normobaric oxygen pretreat- ment improved neurological deficits and reduced infarct volume. Immunohistochemical staining and western blot assay revealed that the expression of hypoxia-inducible factor-la, Notch-l, vascular endothelial growth factor and erythropoietin were increased. Behavioral studies also verified that neurological deficit scores increased. The hypoxia-inducible factor inhibitor 2-methoxyestradiol treatment at 1 hour before administration of normobaric oxygen could suppress the protective effect of normobaric oxygen. Given these observations, normobaric oxygen pretreatment may alleviate cerebral ischemic injury via the hypoxia-inducible factor signal pathway.展开更多
基金National Natural Science Foundation of China(No.30500610)
文摘Acute myocardial ischaemia is a common acute .disease and a common cause of sudden death.However, it is difficult to diagnose in patients who died within 6 hours after the onset of myocardial ischaemia. The occurrence of sudden cardiac death often has pathological basis of primary heart diseases, which may lead to a series of changes in metabolism and gene expression.1 Recent research found that hypoxia inducible factor 1 alpha （HIF-1α） is a sensitive marker of hypoxia; its gene expression is upregulated within several minutes after acute myocardial ischaemia, followed by the upregulation of its protein and its expression will remain high if the inducement continues. Its expression in nonhypoxic cardiac muscle is very low. This characteristic may be used to differentiate hypoxic factors from nonhypoxic factors, and help to judge the cause of death. This study explored the expression of HIF-1α in hypoxic cardiac muscle by establishing an acute myocardial ischaemia model in mice, and observed its dynamic changes to provide reference for analysing causes of death within 48 hours after death.
基金supported by grants from the National Natural Science Foundation of China, No.30973510Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry, No. K513400110a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘This study used a novel combination of in vivo and in vitro experiments to show that Braintone had neuroprotective effects and clarified the molecular mechanisms underlying its efficacy. The Chinese herbal extract Braintone is composed of Radix Rhodiolase Essence, Radix Notoginseng Essence, Fofium Ginkgo Essence and Rhizoma Chuanxiong. In vivo experiments showed that cerebral infarction volume was reduced, hemispheric water content decreased, and neurological deficits were alleviated in a rat model of permanent middle cerebral artery occlusion after administration of 87.5, 175 or 350 mg/kg Braintone for 7 consecutive days. Western blot analysis showed that Braintone enhanced the expression of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothe- lial growth factor in the ischemic cortex of these rats. The 350 mg/kg dose of Braintone produced the most dramatic effects. For the in vitro experiments, prior to oxygen-glucose deprivation, rats were intragastrically injected with 440, 880 or 1 760 mg/kg Braintone to prepare a Braintone-co ntaining serum, which was used to pre-treat human umbilical vein endothelial cells for 24 hours. Human umbilical vein endothelial cell injury was alleviated with this pre-treatment. Western blot and real-time PCR analysis showed that the Braintone-containing serum increased the levels of hy- poxia-inducible factor la mRNA and protein, heine oxygenase-1 protein and vascular endothelial growth factor mRNA in oxygen-glucose deprived human umbilical vein endothelial cells. The 1 760 mg/kg dose produced the greatest increases in expression. Collectively, these experimental findings suggest that Braintone has neuroprotective effects on ischemia-induced brain damage via the up-regulation of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothelial growth factor expression in vascular endothelial cells.
基金supported by National Natural Science Foundation of China (Grant number:31471135,31701040, and 31801003)Shanghai Sailing Program (Grant number: 17YF1418000)Shanghai Municipal Education Commission (Grant number:Chenguang Program 16CG57)
文摘Background:Exercise induces blood flow redistribution among tissues,leading to splanchnic hypoperfusion.Intestinal epithelial cells are positioned between the anaerobic lumen and the highly metabolic lamina propria with an oxygen gradient.Hypoxia-inducible factor(HIF)-la is pivotal in the transcriptional response to the oxygen flux.Methods:In this study,the pimonidazole hydrochloride staining was applied to observe the tissue hypoxia in different organs,which might be affected by the blood flow redistribution.The HIF-la luciferase reporter ROSA26 oxygen-dependent degradation domain(ODD)-Luc/^+mouse model(ODD domain-Luc;female,n=3-6/group) was used to detect the HIF-la expression in the intestine.We used 3 swimming models:moderate exercise for 30 min,heavy-intensity exercise bearing 5% bodyweight for 1.5 h,and long-time exercise for 3 h.Results:We found that 1 session of swimming at different intensities could induce tissue hypoxia redistribution in the small intestine,colon,liver and kidney,but not in the spleen,heart,and skeletal muscle.Our data showed that exercise exacerbated the extent of physiological hypoxia in the small intestine.Next,using ODD-Luc mice,we found that moderate exercise increased the in vivo HIF-1α level in the small intestine.The postexercise HIF-1α level was gradually decreased in a time-dependent manner.Interestingly,the redistribution of tissue hypoxia and the increase of HIF-la expression were not related to the exercise intensity and duration.Conclusion:This study provided evidence that the small intestine is the primary target organ for exercise-induced tissue hypoxia and HIF-la redistribution,suggesting that HIF-1α may be a potential target for the regulation of gastrointestinal functions after exercise.
基金supported by the National Natural Science Foundation of China,No.81000523the grant from Peking University Health Science Center for the New Teacher Funding,No.BMU20090463
文摘Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/ reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxi- dative stress. By contrast, normobaric oxygen has the rapid and non-invasive characteristics and may have therapeutic effects on ischemic/hypoxic disease. Rats inhaled normobaric oxygen （95% 02） for 6 consecutive days, and then a rat model of focal cerebral ischemia was established. Nisst and 2,3,5-triphenyltetrazolium chloride （TTC） staining revealed that normobaric oxygen pretreat- ment improved neurological deficits and reduced infarct volume. Immunohistochemical staining and western blot assay revealed that the expression of hypoxia-inducible factor-la, Notch-l, vascular endothelial growth factor and erythropoietin were increased. Behavioral studies also verified that neurological deficit scores increased. The hypoxia-inducible factor inhibitor 2-methoxyestradiol treatment at 1 hour before administration of normobaric oxygen could suppress the protective effect of normobaric oxygen. Given these observations, normobaric oxygen pretreatment may alleviate cerebral ischemic injury via the hypoxia-inducible factor signal pathway.
