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Hypothermia ameliorates gastrointestinal ischemic injury sustained in a porcine cardiac arrest model

Chinese Medical Journal 2012年第24期125卷 4406-4411页

作者： LU Yi WANG Shuo LI Chun-sheng Department of Emergency Medicine Beijing Chaoyang Hospital Capital Medical University Beijing 100020 China

Background During cardiac arrest, the gastrointestinal tract is sensitive to ischemia. Protection of the gastrointestinal tract is a critical factor in determining prognosis following cardiopulmonary resuscitation （CPR）. This study seeks to determine the extent of gastrointestinal tract injury and the potential protective effect of inducing hypothermia following a porcine cardiac arrest model and CPR. Methods Ventricular fibrillation was induced by programmed electrical stimulation in 16 male domestic pigs （n=8 per group）. Four minutes after ventricular fibrillation, CPR was performed. Pigs that successfully restored spontaneous circulation then received intravenous infusions of saline at either 4℃ or room temperature to produce hypothermic and control conditions respectively. Serum diamine oxidase and gastrointestinal adenosine triphosphate enzyme activity were determined and histopathology of the gastrointestinal tract was performed by light microscopy and electron microscopy. Results Significant injury of the gastrointestinal tract after CPR was found. Na＋-K＋ and Ca2＋ adenosine triphosphate enzyme activity in the gastric tissue were significantly high in animals receiving hypothermia treatment compared to controls. Hypothermia also significantly reduced serum diamine oxidase after CPR compared to the control group. Moreover, severe injury sustained by the gastrointestinal tissue was significantly ameliorated under hypothermic conditions compared to controls. Conclusions Gastrointestinal injury and abnormal energy metabolism are strikingly evident following CPR. Hypothermia, which is induced by an infusion of 4℃ saline, can rapidly reduce internal body temperature, improve energy metabolism, and ameliorate injury to the gastrointestinal mucosa after CPR.

关键词： cardiac arrest cardiopulmonary resuscitation gastrointestinal tract hypothermia ischemic injury

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Acupuncture activates signal transduction pathways related to brain-tissue restoration after ischemic injury

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Neural Regeneration Research 2012年第24期7卷 1866-1872页

作者： Haomei Tian Hong Zhang Junbao Zhu Juan Zhang Hening Cai Yuchen Zhang Chutao Chen Key Laboratory of Meridians and Viscera Hunan University of Traditional Chinese MedicineChangsha 410007Hunan ProvinceChina Liuzhou Hospital of Traditional Chinese Medicine Liuzhou 545001Guangxi Zhuang Autonomous RegionChina Ningxiang Hospital of Traditional Chinese Medicine Ningxiang 410600Hunan ProvinceChina Postgraduate College Hunan University of Traditional Chinese MedicineChangsha 410007Hunan ProvinceChina Laboratory of Acupuncture Bioinformatics Hunan University of Traditional Chinese MedicineChangsha 410007Hunan ProvinceChina

A middle cerebral artery occlusion-model was established in rats using the improved thread embolism *** were treated with acupuncture at either Dazhui（DU14）,Renzhong（DU26）, Baihui（DU20）,or a non-meridian *** with protein-chip technology showed that the level of protein phosphorylation in both groups was upregulated or downregulated depending on the signaling pathway compared with the model group that did not receive *** of proteins showing downregulated phosphorylation revealed that five signaling pathways were activated in the acupuncture-treatment group,while only two were activated in the acupuncture-control *** contrast,analysis of proteins showing upregulated phosphorylation revealed only one pathway was activated in the acupuncture-treatment group,whereas four pathways were activated in the acupuncture-control ***,the number of activated proteins in the acupuncture-treatment group was not only higher than the acupuncture-control group,but unlike the acupuncture-control group,the majority of activated proteins were key proteins in the signaling *** findings indicate that acupuncture at specific points can activate multiple signaling pathways to promote the restoration of brain tissue following ischemic injury,and that this is based on a combination of effects resulting from multiple pathways,targets,and means.

关键词： acupuncture cerebral ischemia Dazhui Baihui Renzhong protein-chip technology signal-transduction pathways nerve injury brain injury ischemic injury neural regeneration

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Kanglexin, a novel anthraquinone compound,protects against myocardial ischemic injury in mice by suppressing NLRP3 and pyroptosis

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中国药理学与毒理学杂志 2019年第10期 770-771页

作者： BIAN Yu LI Xin PANG Ping WANG Ning WANG Jin-hui XIAO Wei DU Wei-jie YANG Bao-feng Department of Pharmacology Harbin Medical University Department of Medicinal Chemistry and Natural Medicine Chemistry Harbin Medical University Jiangsu Kanion Pharmaceutical Co. Ltd.

OBJECTIVE To investigate the myocardial protection effect of a novel anthraquinone compound（4,5-dihydroxy-7-methyl-9,10-anthraquinone-2-ethyl succinate） named Kanglexin（KLX） in vivo and in vitro. METHODS Male C57 BL/6 mice were pre-treated either with KLX(20, 40 mg·kg;·d;, ig) or vehicle for 7 consecutive days prior to ligation of coronary artery to induce permanent MI. Neonatal mouse cardiomyocytes（NMCMs） were exposed to hypoxia or LPS to detect the myocardial protection effect of KLX. Echocardiographic and myocardial infarct size were used to evaluate the effect of KLX on MI treated mice. Electron microscopic examination and H&E staining were preformed to determine morphological changes of each group. Western blotting and q PCR were used to detect the expressions of pyroptosis relative proteins. The numbers of TUNEL and PI-positive cells were measured to assess pyroptotic cell *** KLX reduced myocardial infarct size and LDH release and improved cardiac function as compared to vehicle-treated mice 24 h after MI. We found that MI triggered NLRP3 inflammasome activation leading to conversion of IL-1β and IL-18 into their active mature forms in the heart. We also showed that MI induced pyroptosis, as evidenced by increased DNA fragmentation, mitochondrial swelling and cell membrane rupture as well as increased levels of several pyroptosis-related proteins, including GSDMD, N-GSDMD and cleaved caspase-1. All these detrimental alterations were prevented by KLX administration. In hypoxia-or LPS-treated NMCMs,we showed that 10 μmol·L;KLX decreased the elevated levels of TUNEL-and PI-positive cel s as wel as pyroptosisrelated proteins. CONCLUSION KLX prevents MI-induced cardiac damages and cardiac dysfunction at least partly through attenuating NLRP3 and subsequent cardiomyocyte pyroptosis, and it is worthy of more rigorous investigations for its potential for alleviating ischemic heart disease.

关键词： myocardial infarction anthraquinone Kanglexin ischemic injury NLRP3 inflammasome pyroptosis

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Cell polarization in ischemic stroke: molecular mechanisms and advances

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Neural Regeneration Research 2025年第3期20卷 632-645页

作者： Yuanwei Li Xiaoxiao Xu Xuan Wu Jiarui Li Shiling Chen Danyang Chen Gaigai Li Zhouping Tang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

关键词： astrocyte polarization immune regulation inflammation ischemic injury microglia polarization neutrophil polarization signaling pathways stroke

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Curcumin protects against ischemic spinal cord injury The pathway effect

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Neural Regeneration Research 2013年第36期8卷 3391-3400页

作者： Jinhua Zhang Hao Wei Meimei Lin Chunmei Chen Chunhua Wang Maobai Liu Department of Pharmacy Union Hospital Fujian Medical University Department of Neurosurgery Union Hospital Fujian Medical University

Inducible nitric oxide synthase and N-methyI-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin, Reverse transcrip- tion-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tadov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective ef- fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyI-D-aspartate receptor expression.

关键词： neural regeneration traditional Chinese medicine curcumin spinal cord injury ischemic injury N-methyI-D-aspartate receptor inducible nitric oxide synthase neuroprotection grants-supported paper neuroregeneration

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Induction of ischemic tolerance as a promising treatment against diabetic retinopathy

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Neural Regeneration Research 2014年第17期9卷 1581-1584页

作者： Ruth E.Rosenstein Diego C.Fernandez Laboratory of Retinal Neurochemistry and Experimental Ophthalmology Department of Human BiochemistrySchool of Medicine/CEFyBOUniversity of Buenos Aires/CONICET Present address:Johns Hopkins University Department of Biology

Diabetic retinopathy is a leading cause of acquired blindness, and it is the most common ischemic disorder of the retina. Available treatments are not very effective. Efforts to inhibit diabetic reti- nopathy have focused either on highly specific therapeutic approaches for pharmacologic targets or using genetic approaches to change expression of certain enzymes. However, it might be wise to choose innovative treatment modalities that act by multiple potential mechanisms. The resis- tance to ischemic injury, or ischemic tolerance, can be transiently induced by prior exposure to a non-injurious preconditioning stimulus. A complete functional and histologic protection against retinal ischemic damage can be achieved by previous preconditioning with non-damaging isch- emia. In this review, we will discuss evidence that supports that ischemic conditioning could help avert the dreaded consequences that results from retinal diabetic damage.

关键词： diabetic retinopathy ischemic tolerance retina ischemic injury ischemic conditioning

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Sclerosing cholangitis in critically ill patients： an important and easily ignored problem based on a German experience

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Frontiers of Medicine 2014年第1期8卷 118-126页

作者： Ting Lin Kai Qu Xinsen Xu Min Tian Jie Gao Chun Zhang Ying Di Yuelang Zhang Chang Liu Department of Hepatobiliary Surgery Surgical Intensive Care Unit Department of Imaging the First Affiliated Hospital School ofMedicine Xi 'an Jiaotong University Xi 'an 710061 China

Intensive care unit （ICU） is important in the rehabilitation of critically ill patients. In the past decades, many patients who received aggressive treatment in ICU developed sclerosing cholangitis in multiple centers. Sclerosing cholangitis in critically ill patients （SC-CIP） is a relatively new issue. To investigate the causes, clinical manifestation, treatment, and prognosis of SC-CIP, we searched for published cases in the databases of PubMed, Highwire, and Elsevier from 2001 to 2012. Data were extracted using a standard form and retrospectively analyzed. Twelve eligible studies covering 88 patients, with 64 men and 24 women, were mainly reported by German centers. The mean age was 49.8 years. All of the patients recovered from critical illnesses, such as trauma, infection, burn, and major surgeries. High pressure positive end-expiratory pressure （PEEP, peak level at 12.8 cm H20） was utilized for all patients, with the average duration of 36.3 d. In addition, vasopressor agents were administered in approximately 60% of SC-CIE A rapid increase in cholestasis and irregular strictures in the intrahepatic bile ducts was observed in the following months. With an average follow-up period of 17.9 months, poor outcomes were observed in 54 patients, including 34 deaths. In conclusion, ischemic injury of the biliary tree, which may be affected by PEEP and/or vasopressor administration, affects cholangiopathic procedure. As a newly discovered type of secondary sclerosing cholangitis, SC-CIP is a severe progressive complication of patients in ICU and should be carefully monitored by clinicians.

关键词： intensive care unit sclerosing cholangitis ischemic injury prognosis systemic review

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New-onset hyperglycemia immediately after liver transplantation:A national survey from China Liver Transplant Registry

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Hepatobiliary & Pancreatic Diseases International 2018年第4期17卷 310-315页

作者： Qing-Hong Ke Hai-Tao Huang Qi Ling Ji-Min Liu Si-Yi Dong Xiang-Xiang He Wen-Jin Zhang Shu-Sen Zheng Department of Hepatobiliary Pancreatic Surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Combined Multi-Organ Transplantation Ministry of Public HealthHangzhou 310003China Department of Pathology and Molecular Medicine Faculty of Health SciencesMcMaster UniversityHamiltonON L8S 4L8Canada China Liver Transplant Registry Hangzhou 310003China

Background: New-onset hyperglycemia(NOH) is a common phenomenon after liver transplantation(LT),but its impact on clinical outcomes has not yet been fully assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month after ***: The data of 3339 adult patients who underwent primary LT from donation after citizen death between January 2010 and June 2016 were extracted from China Liver Transplant Registry database and analyzed. NOH was defined as fasting blood glucose ≥7.0 mmol/L confirmed on at least two occasions within the first post-transplant month with or without hypoglycemic ***: Of 3339 liver recipients, 1416(42.4%) developed NOH. Recipients with NOH had higher incidence of post-transplant complications such as graft and kidney failure, infection, biliary stricture, cholangitis,and tumor recurrence in a glucose concentration-dependent manner as compared to non-NOH recipients(P ischemic time >10 min, cold ischemic time >10 h, anhepatic time >60 min, recipient model for end-stage liver disease score >30, moderate ascites and corticosteroid usage(P ischemic injury may help maintain glucose homeostasis.

关键词： New-onset hyperglycemia Liver transplantation Surveillance ischemic injury Homeostasis

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A reliable graded acute liver failure model in rats: treatment with internal bioartificial liver

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Hepatobiliary & Pancreatic Diseases International 2004年第2期3卷 254-258页

作者： Qing-Xiang Xu, Yi-Tao Ding, Yu-Dong Qiu, De-Cai Yu and He-Yuan Zhang Nanjing, China Department of Hepatobiliary Surgery, Drum Tower Hospital, Medical College of Nanjing University, and Hepatobiliary Institute of Nanjing University Hepatobiliary Surgery Institute of Nanjing Biochemistry Department of Nanjing University, Nanjing 210008 , China Department of Hepatobiliary Surgery Drum Tower Hospital Nanjing 210008 China. xqx008@***

BACKGROUND: Appropriate animal models are impor- tant for studying acute liver failure. This study was to assess a new suitable rat model for acute liver failure. METHODS: After the right influent hepatic vessels were clamped for a period of time (45, 60 or 90 minutes respec- tively), the animal model was established by removal of the clamp for restoring blood flow of the right lobes while im- mediately removal of the median, left lateral and caudate lobes. Animal survival rate was observed in the following 14 days in each group. To study the pathophysiological chan- ges of the model, some biochemical parameters in 5 con- secutive days were evaluated in the 60-minute group. Inter- nal bioartificial liver was transplanted in the peritoneal cavi- ty to test the reversibility of the model. RESULTS: The survival rate of the models decreased, as the ischemia time of the right lobes prolonged to zero in the 90-minute group, to 50% in the 60-minute group and to 100% in the 45-minute group on the fifth day after opera- tion. The levels of ammonia, alanine aminotransferase, al- kaline phosphatase, total bilirubin and prothrombin were elevated dramatically 12 to 24 hours after operation in the 60-minute group. When internal bioartificial liver was transplanted, the survival rate increased significantly in ad- dition to the levels of ammonia and total bilirubin. CONCLUSION: A period time of ischemic injury in the right lobe followed by 70% liver resection can produce a graded acute hepatic failure model in rats.

关键词： acute liver failure hepatectomy ischemic injury internal bioartificial liver

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BUILDING OF A SIMPLE MODEL OF AUTO-OLT IN DOGS AND ITS SIGNIFICANCE

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Journal of Pharmaceutical Analysis 1996年第2期10卷 155-158页

作者：康亚安黎一鸣纪宗正秦兆寅

AIM: we recommend a method of Simple auto-oLT model in ***:The model was ligated all ligaments or connective tissues of the liver,only reserved the vascular construction,that was the suprahepatic and infrahepatic inferior vena cava,portal vein,hepatic artery or common bile *** operation was similar to the orthotopic liver transplantation except vascular anastomoses,the dog liver underwent the warm or cold ischemia and the reperfusated injurous ***: The imitability was exactly good and the operation was simple and safe. Because the hepatic vessels of the going out or coming in was clamped block and might open or blind the blood flow whenever necessary,the model might control the warm or cold ischemic time accurately,and eliminate the influence or the complications due to vascular ***: The model avoided many-sided Influences of the traditional OLT and was a good method to study hepatic artery or portal vein ischemic injury and created a new way to explore the pathogenesis or some complications in the OLT.

关键词： dog liver auto-orthotopic transplantation model ischemic injury complication

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