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Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury

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World Journal of Clinical Cases 2023年第3期11卷 487-492页

作者： Yi-Chao Wang Meng-Jun Wu Sheng-Liang Zhou Zhi-Hui Li Department of Thyroid&Parathyroid Surgery Center West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Laboratory of Thyroid and Parathyroid Disease Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Anesthesiology Chengdu Women and Children's Central HospitalSchool of MedicineUniversity of Electronic Science and TechnologyChengdu 610041Sichuan ProvinceChina

Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury(I/R).The guidelines for CPR suggest the use of therapeutic hypothermia(TH)as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury.During TH,sedative agents(propofol)and analgesia agents(fentanyl)are commonly used to prevent shiver and pain.However,propofol has been associated with a number of serious adverse effects such as metabolic acidosis,cardiac asystole,myocardial failure,and death.In addition,mild TH alters the pharmacokinetics of agents(propofol and fentanyl)and reduces their systemic clearance.For CA patients undergoing TH,propofol can be overdosed,leading to delayed awakening,prolonged mechanical ventilation,and other subsequent complications.Ciprofol(HSK3486)is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room.Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol.Therefore,we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.

关键词： HSK3486 Therapeutic cerebral ischemia-reperfusion injury Hypothesis

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Network Pharmacology-Based and Pharmacological Evaluation of the Effects of Curcumae Radixon cerebral ischemia-reperfusion injury

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World Journal of Traditional Chinese Medicine 2023年第2期9卷 201-211页

作者： Shang-Xia Zhang Yu-Hong Wang Hong-Ping Long Jian Liu Hong-Qing Zhao Jian Yi Jia Ling Science and Technology Innovation Center/State Key Laboratory Breeding Base of Chinese Medicine Powder and Innovative Medicine Hunan University of Chinese Medicine Changsha 410208China Central Laboratory The First Affiliated Hospital of Hunan University of Chinese Medicine Changsha 410007China

Objective: This study aimed to investigate the network pharmacology of curcumae radix(CR, Yujin) and explore the mechanism of CR in the treatment of cerebral ischemia-reperfusion injury(CIRI). Materials and Methods: Network analysis and pharmacological evaluation were performed to explore the protective role of CR to treat CIRI. The potential target genes of the active components and CIRI were identified using SwissTarget Prediction, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, GeneCards, and Online Mendelian Inheritance in Man. Furthermore, network analysis was performed using Cytoscape software.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the R software. In vivo experiments were performed using the water extract of CR(WECR) on PC12 cells induced by hypoxia/reoxygenation(H/R) to simulate ischemia/reperfusion injury. Results: The results exhibited that 21 active compounds identified in CR were associated with 73 targets of CIRI. Functional analysis showed that multiple pathways, including response to stress, regulation of apoptotic process, and hypoxia-inducible factor 1 signaling pathway, were significantly enriched. In addition, STAT3, IL4, HIFIA, and CTNNB1 were predicted to be the most important genes among the 36 hub genes. Furthermore, WECR treatment significantly improved PC12 cell injury and decreased apoptosis levels in cells induced by H/R, with malondialdehyde contents reduced and superoxide dismutase or glutathione peroxidase levels increased. Conclusions: Network analysis and pharmacological evaluation of CR could provide valuable directions for further research on CR and improve comprehension of CIRI.

关键词： cerebral ischemia-reperfusion injury curcumae radix network pharmacology pharmacological evaluation

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Research Progress on the Pharmacological Mechanisms of Chinese Medicines that Tonify Qi and Activate Blood Against cerebral ischemia/reperfusion injury

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World Journal of Traditional Chinese Medicine 2022年第2期8卷 225-235页

作者： Xiao-Yu Zheng Ye-Hao Zhang Wen-Ting Song Dennis Chang Jian-Xun Liu Beijing University of Chinese Medicine Graduate SchoolBeijing 100029 Institute of Basic Medical Sciences of Xiyuan Hospital China Academy of Chinese Medical SciencesBeijing Key Laboratory of Pharmacology of Chinese MateriaBeijing 100091China NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2751Australia

cerebral ischemia-reperfusion injury(CIRI) refers to a pathological phenomenon that aggravates the injury after the restoration of blood perfusion and oxygen supply to the cerebral ischemia-induced tissues and organs, with a relatively high incidence. The traditional Chinese medicine(TCM) believes that Qi deficiency and blood stasis are the cause of CIRI. Therefore, Chinese medicine for tonifying Qi and activating blood is regarded as an important choice for the treatment of CIRI. In recent years, it has been found that many Chinese herbal medical ingredients and compound Chinese medicine(CCM) have significant anti-CIRI effects, and their mechanisms of action mainly include improving brain blood supply, neuroprotection, regulating signal pathways such as TLR4/HO-1/Bcl-2, protecting mitochondrial function, regulating related protein levels, and regulating oxidative molecule levels. This article summarizes and introduces the pharmacological mechanisms of Tonifying-Qi and activating-blood Chinese medicine and CCM which have the function of anti-CIRI. Our goal is to provide effective reference for further researches on the cerebral protection of related TCMs or compounds and their clinical application.

关键词： cerebral ischemia-reperfusion injury compound Chinese medicine ingredients of traditional Chinese medicine Qi deficiency and blood stasis Tonifying Qi and activating blood

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Salvianolate increases heat shock protein expression in a cerebral ischemia-reperfusion injury model

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Neural Regeneration Research 2013年第25期8卷 2327-2335页

作者： Jinnan Zhang Wei Lu Qiang Lei Xi Tao Hong You Pinghui Xie Department of Neurology Second Xiangya HospitalCentral South University

Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi- crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue following ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneally injected with salvianolate （18 mg/kg） or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smaller infarct area and a significantly lower number of apoptotic cells were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.

关键词： neural regeneration traditional Chinese medicine brain injury salvianolic acid B salvianolate heatshock protein 22 protein kinase B cerebral ischemia-reperfusion injury apoptosis neuroprotection neuroregeneration

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Effects of repetitive transcranial magnetic stimulation on adenosine triphosphate content and microtubule associated protein-2 expression after cerebral ischemia-reperfusion injury in rat brain

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Chinese Medical Journal 2008年第14期121卷 1307-1312页

作者： FENG Hong-lin YAN Li CUI Li-ying Department of Neurology First Hospital of Harbin Medical University Harbin Heilongjiang 150001 China Department of Neurology China-Japan Friendship Hospital of Beijing Beijing 100029 China Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China

Background Repetitive transcranial magnetic stimulation （rTMS） research has mainly been focused on the therapeutic effect of psychiatric disorders and Parkinson＇s disease. A few studies have shown that rTMS might protect against delayed neuronal death induced by transient ischemia, enhance long-term potentiation in ischemic conditions and affect regional brain blood flow and metabolism. The aim of this study was to determine the effects of repetitive transcranial magnetic stimulation （rTMS） on adenosine triphosphate （ATP） content and microtubule associated protein-2 （MAP-2） expression in rat brain after middle cerebral artery occlusion （MCAO）/reperfusion. Methods To study the effects of different timecourses of rTMS on ATP content and MAP-2 expression, 90 rats were randomly divided into three groups （30 rats in each group）. To study the effects of multiple rTMS parameters on ATP content and MAP-2 expression, the rats in each group were further divided into six subgroups （five rats each）. The rats were sacrificed at 1-hour, 24-hour and 48-hour intervals after reperfusion, and the brain tissues were collected for the detection of ATP and MAP-2. Results rTMS could significantly increase ATP content and MAP-2 expression in the left brain following ischemic insult （P 〈0.01） and different rTMS parameters had different effects on the ATP level and the MAP-2 expression in the left striatum. A high-frequency rTMS played an important role in MAP-2 expression and ATP preservation. Conclusions This study revealed that rTMS induced significant increase of ATP content and MAP-2 expression in the injured area of the brain, suggesting that the regulation of both ATP and MAP-2 may be involved in the biological mechanism of the effect of rTMS on neural recovery. Therefore, rTMS may become a potential adjunctive therapy for ischemic cerebrovascular disease.

关键词： transcranial magnetic stimulation repetitive cerebral ischemia-reperfusion injury adenosine triphosphate microtubule associated protein-2

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Enhanced treatment for cerebral ischemia-reperfusion injury of puerarin loading liposomes through neutrophils-mediated targeted delivery

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Nano Research 2021年第12期14卷 4634-4643页

作者： Wei Liu Haowei Lu Xiaoyong Rao Xiang Li Hongdan Lu Feifei Li Yan He Riyue Yu Rongsheng Zhong Yao Zhang Xiaojian Luo Hongliang Xin National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine Jiangxi University of Traditional Chinese MedicineNanchang330006China The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine Nanchang330006China Department of Pharmaceutics and Key Laboratory of Cardiovascular&Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing211166China Department of Pharmacy Kangda College of Nanjing Medical UniversityLianyungang222000China

The recovery of blood circulation following cerebral infarction-associated thrombolysis brings new damage to the brain,which is cerebral ischemia-reperfusion injury(CIRI).Inflammation is the main pathological mechanism of CIRI.The inflammatory response triggered by cerebral ischemia-reperfusion provides neutrophils with a special opportunity to facilitate drug delivery to the site of ischemic penumbra through the chemotaxis of inflammatory factors by neutrophils.Puerarin is an isoflavone derivative with a significant neuroprotective effect in vitro.But the blood-brain barrier(BBB)impedes its therapeutic efficacy on CIRI within the brain.Inspired by the pathological process,we have used neutrophils as carriers to enhance the BBB penetration of liposomes loaded with puerarin and improve the concentration of puerarin in the brain parenchyma in this study.These results showed that puerarin-containing liposomes were released in response to inflammatory conditions associated with brain injury to enhance the neuroprotection effect at the ischemic penumbra.

关键词： cerebral ischemia-reperfusion injury neuroprotection neutrophils puerarin liposomes

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Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global cerebral ischemia-reperfusion injury in Rats

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Chinese Journal of Integrative Medicine 2009年第1期15卷 54-59页

作者：吴海琴郭荷娜王虎清常明则张桂莲赵英贤 Department of Neurology the Second Affiliated HospitalMedical College of Xi'an Jiaotong University

Objective:To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats,and to explore its mechanism of action.Methods:The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats.Rats were intraperitoneally injected with puerarin(100 mg/kg) 1 h before ischemia and once every 6 h afterwards.The learning-memory ability was evaluated by the passive avoidance test.Th...

关键词： puerarin cerebral ischemia-reperfusion injury learning-memory disorder

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Expression of nerve growth factor precursor, mature nerve growth factor and their receptors during cerebral ischemia-reperfusion injury

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Neural Regeneration Research 2011年第22期6卷 1701-1708页

作者： Guoqian He Jian Guo Jiachuan Duan Wenming Xu Ning Chen Hongxia Li Li He Department of Neurology West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China Joint Laboratory of Reproductive Medicine Sichuan University-The Chinese University of Hongkong Joint Laboratory for Reproductive Medicine （SCU-CUHK） Institute of Women and Children＇s Health Department of Obstetrics and Gynecology West China Second University Hospital Sichuan University Chengdu 610041 Sichuan Province China

We investigated nerve growth factor precursor （proNGF） and mature NGF expression in ischemic and non-ischemic cortices after cerebral ischemia-reperfusion injury. In both ischemic and non-ischemic cortices, proNGF was found to be present in the extracellular space and cytoplasm. In addition, mature NGF was expressed in extracellular space, but with a very low signal. In ischemic cortex only, proNGF was significantly decreased, reaching a minimal level at 1 day. Mature NGF was increased at 4 hours, then reached a minimal level at 3 days. The p75 neurotrophin receptor （p75NTR） was significantly decreased after ischemia, and increased at 3 days after ischemia. These results confirmed that proNGF was the predominant form of NGF during the pathological process of cerebral ischemia-repeffusion injury. In addition, our findings suggest that ischemic injury may influence the conversion of proNGF to mature NGF, and that proNGF/p75NTR may be involved in reperfusion injury.

关键词： cerebral ischemia-reperfusion injury nerve growth factor precursor mature nerve growth factor p75 neurotrophin receptor cell apoptosis

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Protection of Salvianolate Lyophilized Injection combined with Xueshuantong Injection (Lyophilized) against focal cerebral ischemia/reperfusion injury in rats through suppression of inflammatory response

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Chinese Herbal Medicines 2018年第1期10卷 46-53页

作者： fu-jiang wang zuo-yan sun rui-lin li li-min hu li-juan chai shao-xia wang hong guo yue zhang tianjin state key laboratory of modern chinese medicine tianjin university of traditional chinese medicinetianjin 300193China key laboratory of formula of traditional chinese medicine ministry of educationtianjin university of traditional chinese medicinetianjin 300193China

Objective： Inflammatory reactions induced by microglia in the brain play an important part in the pathogenesis of focal cerebral ischemia/reperfusion （I/R） injury, resulting in neuronal death. Salvianolate Lyophilized Injection （SLI） and Xueshuantong Injection （Lyophilized）（XST）, which have been widely used in the treatment of acutely cerebral infarction clinically in China, exhibit various biological activities. In this study, the neuroprotective properties of SLI combined with XST in a rat model of middle cerebral artery occlusion- reperfusion （MCAO/R） were investigated. Methods： In this study, male Wistar rats were subjected to 1.5h of middle cerebral artery occlusion followed by reperfusion for 24 h. The rats were randomly divided into the following six groups： normal group （NOR）, model group （MOD）, SLI group （21 mg/kg, SLI）, ）（ST group （100 mg/kg, ）（ST）, SLI combined with XST （XST 100 mg/kg ＋ SLI 21 mg/kg, 1X1S）, and Edaravone （as a positive control drug, 6 mL/kg, EDI）, once a day for 3 d. The neuronal injury, the expression of glial fibrillary acidic protein （GFAP） and ionized calcium binding adaptor molecule 1 （IBA-1）, and the changes of pro-inflammatory mediators interleukin- 6 （IL-6）, tumor necrosis factor alpha （TNF-α） and anti-inflammatory mediator interleukin-10 （IL-10） were observed. Results： 1X1S treatment significantly increased the number of neuron, compared with the MOD group, SH group and XST group. Gliosis （GFAP and IBA-1） and expression of pro-inflammatory mediators IL-6 and TNF-a were significantly reduced. Meanwhile, 1XIS significantly increased the expression of anti- inflammatory mediator IL-10 in the brains of MCAO/R rats, compared with the MOD group, SLI and XST groups. SLI and XST also remarkably down-regulated the expression of IL-6 and TNF-α compared with the MOD group. Conclusions： This study shows that SLI combined with XST （1X1S） can protect cerebral ischemia- reperfusion injury due to its anti-inflammatory property, and may provide a potential promising new therapeutic strategy f

关键词： cerebral ischemia-reperfusion injury inflammatory reaction Salvianolate Lyophilized Injection Xueshuantong Injection （Lyophilized）

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The effect of hyperglycemia on blood brain barrier of rats with focal cerebral ischemia/reperfusion injury

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Journal of Nanjing Medical University 2005年第5期19卷 241-246页

作者： Hongxin Wang Yuanwu Mei Neurology Department Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022. China

Objective： To determine whether hyperglycemia could aggravate the microvascular damage in ischemic stroke. Methods： Hyperglycemia model was made by injection of streptozocin through subcutaneous injection in wistar rats. Using the suture model, the rats were subjected to 3h of focal ischemia and different times of reperfusion, including 6,12,24,48,96h and 7d. TIC dyeing was used to Show the infarction area of rats. The infarctive volume of rats were calculated by computer imaging analysis system;Matrix metalloproteinase （MMP-2） and （MMP-9）were detected by immunohistochemistly and in situ hybridization histochemistly in Wistar rats. Results： The infarctive volume was siginificantly larger in hyperglycemic rats than that of nonhyperglycemic rats. The level of MMP-2, MMP-9 expression in the group of hyperglycemic rats was higher than that of nonhyperglycemic rats. Conclusion： Hyperglycemia aggravated the injury of focal ischmia-repeffusion in wistar rats and the higher expression of MMP-2,MMP-9 might be one of the mechanism in aggravation of focal ischemia/repeffusion injury.

关键词： hyperglycemia cerebral ischemia-reperfusion injury MMP-2 MMP-9

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