Ischemic stroke is one of the most common public diseases that increase mortality.In the ischemic brain,blood flow restoration can cause the generation of excess reactive oxygen species(ROS).Endogenous anti-oxidases i...Ischemic stroke is one of the most common public diseases that increase mortality.In the ischemic brain,blood flow restoration can cause the generation of excess reactive oxygen species(ROS).Endogenous anti-oxidases in the living system,including catalase(CAT)and superoxide dismutase(SOD),can consume the excess ROS by catalysis to regulate inflammation.However,these natural enzymes are difficult to be widely used in the treatment of stroke.Taking advantages of high stability,low cost,and long-term storage,antioxidative nanozymes-mediated treatments have been proven as a promising method against ischemic stroke.To highlight the progress,we summarize the advances in nanozymes with the antioxidative ability for treating ischemic stroke.It is believed that such a promising therapeutic strategy of antioxidative nanozymes will significantly contribute to the field of ischemic stroke.We expect that antioxidative nanozymes will play significant roles in both basic research and clinical applications.展开更多
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin an...Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.展开更多
基金supported by the National Natural Science Foundation of China (82102335 and 82101184)the Postdoctoral Science Foundation of China (2021TQ0218 and 2022M722207)+5 种基金Shenzhen Fundamental Research Program (JCYJ20210324102809024)Shenzhen PhD Start-up Program (RCBS20210609103713045)the International Coop-erative Project of Shenzhen Science and Technology Innovation Committee (GJHZ20200731095602009)the Shenzhen Key Laboratory of Translational Medicine of Biomaterials,the Science and Technology Innovation Commission of Shenzhen (ZDSYS20200811142600003)the Shenzhen Medical Cure and Prevention Integration Program of Nervous System Diseasethe Quality Control and Improvement Program of Treatment of Acute Ischemic Stroke.
文摘Ischemic stroke is one of the most common public diseases that increase mortality.In the ischemic brain,blood flow restoration can cause the generation of excess reactive oxygen species(ROS).Endogenous anti-oxidases in the living system,including catalase(CAT)and superoxide dismutase(SOD),can consume the excess ROS by catalysis to regulate inflammation.However,these natural enzymes are difficult to be widely used in the treatment of stroke.Taking advantages of high stability,low cost,and long-term storage,antioxidative nanozymes-mediated treatments have been proven as a promising method against ischemic stroke.To highlight the progress,we summarize the advances in nanozymes with the antioxidative ability for treating ischemic stroke.It is believed that such a promising therapeutic strategy of antioxidative nanozymes will significantly contribute to the field of ischemic stroke.We expect that antioxidative nanozymes will play significant roles in both basic research and clinical applications.
基金supported by the National Natural Science Foundation of China,No.81430102(to QGW)
文摘Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.
