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A comprehensive neuromonitoring approach in a large animal model of cardiac arrest

Animal Models and Experimental Medicine 2022年第1期5卷 56-60页

作者： Filippo Annoni Lorenzo Peluso Lucas Akira Hirai Giovanni Babini Amina Khaldi Antoine Herpain Lorenzo Pitisci Lorenzo Ferlini Bruno Garcia Fabio Silvio Taccone Jacques Creteur Fuhong Su Intensive Care Experimental Laboratory Intensive Care UnitErasme HospitalBrusselBelgium Intensive Care Unit São Domingos HospitalSão LuísBrazil Department of Pathophysiology and Transplants University of MilanMilanItaly Department of Anesthesiology Intensive Care and Emergency Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly

Background:Anoxic brain injuries represent the main determinant of poor outcome after cardiac arrest(CA).Large animal models have been described to investigate new treatments during CA and post-resuscitation phase,but a detailed model that includes extensive neuromonitoring is lacking.Method:Before an electrically-induced 10-minute CA and resuscitation,46 adult pigs underwent neurosurgery for placement of a multifunctional probe(intracranial pressure or ICP,tissue oxygen tension or PbtO_(2) and cerebral temperature)and a bolt-based technique for the placement and securing of a regional blood flow probe and two sEEG electrodes;two modified cerebral microdialysis(CMD)probes were also inserted in the frontal lobes and accidental misplacement was prevented using a perforated head support.Result:42 animals underwent the CA procedure and 41 achieved the return of spontaneous circulation(ROSC).In 4 cases(8.6%)an adverse event took place during preparation,but only in two cases(4.3%)this was related to the neurosurgery.In 6 animals(13.3%)the minor complications that occurred resolved after probe repositioning.Conclusion:Herein we provide a detailed comprehensive neuromonitoring approach in a large animal model of CA that might help future research.

关键词： anoxic injury heart arrest ischemiareperfusion post-arrest resuscitation

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Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress

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Maternal-Fetal Medicine 2022年第1期4卷 7-16页

作者： Tingting Xu Daijuan Chen Xixi Deng Yongchi Zhan Fan Zhou Xiaodong Wang Department of Obstetrics and Gynecology West China Second University HospitalSichuan UniversitySichuan 610041China Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University) Ministry of EducationSichuan 610041China

Objective:To investigate the possible regulatory mechanism of corticotropin-releasing hormone(CRH),urocortin(UCN),and Wolfram syndrome 1(WFS1)in 17α-ethynylestradiol(EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion(IR)model.Methods:Pregnant rats(n=60)were randomly divided into four experimental groups by random number table(Control,EE,IR,and EE-IR groups),and were studied on the 17^(th),19th,and 21st gestational days(GD)(n=5 in each group at the indicated time).Growth and development indicators of fetal rats among these four groups were recorded.Enzyme-linked immunosorbent assay was employed to detect CRH,UCN,and WFS1 levels in maternal sera.Western blotting and real-time polymerase chain reaction were used to quantify placental protein and placental mRNA levels of CRH,UCN,and WFS1.Multivariate analysis of variance and least significant difference test were used to establish the group and individual comparisons.Results:A significant difference was found in placenta weight(F=8.10,P0.05),and IR(0.46±0.15vs.0.22±0.15,P>0.05)groups at 19th GD,indicating that endoplasmic reticulum stress may be activated.However,the expression of CRH(0.42±0.05vs.0.58±0.12,P0.05),and WFS1(0.57±0.07vs.0.74±0.12,P>0.05)protein in the EE-IR group was subsided compared to the IR group at 17^(th) GD.Conclusion:Fetal rat growth restriction was found in the EE-induced intrahepatic cholestasis model.This study revealed that significant changes in the maternal sera level of UCN,placental level of WFS1 mRNA and placental levels of CRH,UCN,

关键词： Cholestasis,intrahepatic Pregnancy Compensatory vasodilatory effect WFS1 CRH family peptides ischemiareperfusion

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Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

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Acta Pharmaceutica Sinica B 2019年第2期9卷 335-350页

作者： Jiabing Wang Lili Huang Chanchan Cheng Ge Li Jingwen Xie Mengya Shen Qian Chen Wulan Li Wenfei He Peihong Qiu Jianzhang Wu Chemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Municipal Hospital Affiliated to Medical School of Taizhou University Ningbo Medical Centre Li Huili Hospital College of Information Science and Computer Engineering Wenzhou Medical University

Scavenging reactive oxygen species(ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury(CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2 O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 couldemerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

关键词： Reactive oxygen species Cerebral ischemiareperfusion injury Stroke Dual-antioxidant mechanism Chalcones Antioxidants Oxidative stress NRF2/ARE

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Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats

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World Journal of Gastroenterology 2015年第26期21卷 8081-8088页

作者： Yuan-Yuan Ji Zhi-Dong Wang Shu-Feng Wang Bao-Tai Wang Zheng-An Yang Xiao-Rong Zhou Ni-Na Lei Wei-Na Yue Scientific Research Centre The Second Affiliated HospitalXi’an Jiaotong University Department of VIP General Surgery The Second Affiliated HospitalXi’an Jiaotong University Department of General Surgery The First Affiliated HospitalXi’an Jiaotong University

AIM: To evaluate preventative effects of ischemic preconditioning(IP) in a rat model of intestinal injury induced by ischemia-reperfusion(IR).METHODS: Male Sprague-Dawley rats(250-300 g) were fasted for 24 h with free access to water prior to the operation.Eighteen rats were randomly divided into three experimental groups: S group(n = 6),rats were subjected to isolation of the superior mesenteric artery(SMA) for 40 min,then the abdomen was closed; IRgroup(n = 6),rats were subjected to clamping the SMA 40 min,and the abdomen was closed followed by a 4-h reperfusion; IP group(n = 6) rats underwent three cycles of 5 min ischemia and 5 min reperfusion,then clamping of the SMA for 40 min,then the abdomen was closed and a 4-h reperfusion followed.All animals were euthanized by barbiturate overdose(150 mg/kg pentobarbital sodium,i.v.) for tissue collection,and the SMA was isolated via median abdominal incision.Intestinal histologic injury was observed.Malondialdehyde(MDA),myeloperoxidase(MPO) and tumor necrosis factor(TNF)-a concentrations in intestinal tissue were measured.Intercellular adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 expression,as well as nuclear factor(NF)-κB activity and expression in intestinal tissue were also determined.RESULTS: Compared with the IR group,IP reduced IR-induced histologic injury of the intestine in rats(2.00 ± 0.71 vs 3.60 ± 0.84,P < 0.05).IP significantly inhibited the increase in MDA content(5.6 ± 0.15 μmol/L vs 6.84 ± 0.18 μmol/L,P < 0.01),MPO activity(0.13 ± 0.01 U/L vs 0.24 ± 0.01 U/L,P < 0.01),and TNF-a levels(7.79 ± 2.35 pg/m L vs 10.87 ± 2.48 pg/m L,P < 0.05) in the intestinal tissue of rats.IP also markedly ameliorated the increase in ICAM-1(204.67 ± 53.27 vs 353.33 ± 45.19,P < 0.05) and VCAM-1(256.67 ± 58.59 vs 377.33 ± 41.42,P < 0.05) protein expression in the intestinal tissues.Additionally,IP remarkably decreased NF-κB activity(0.48 ± 0.16 vs 0.76 ± 0.22,P < 0.05) and protein expression(320.23 ± 38.16 vs 520.76 ± 40.53,P < 0.01) in rat intestinal

关键词： Intercellular adhesion molecule ischemiareperfusion Ischemic preconditioning Nuclear factor-κB Tumor necrosis factor-a

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Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory disturbance in rat mesentery

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World Journal of Gastroenterology 2010年第42期16卷 5306-5316页

作者： Ming-Xia Wang Yu-Ying Liu Bai-He Hu Xiao-Hong Wei Xin Chang Kai Sun Jing-Yu Fan Fu-Long Liao ChuanShe Wang Jun Zheng Jing-Yan Han Ming-Xia Wang Tasly Microcirculation Research Center Peking University Health Science Center Beijing 100191 China Department of Pharmacology Tianjin University of Traditional Chinese Medicine Tianjin 300193 China Tasly Microcirculation Research Center Peking University Health Science Center Beijing 100191 China Department of Integration of Chinese and Western Medicine School of Basic Medical SciencesPekingUniversityBeijing 100191China

AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion.Changes in mesenteric microcirculatory variables,including diameter of venule,velocity of red blood cells in venule,leukocyte adhesion,free radicals released from venule,albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope.Meanwhile,the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry.Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.RESULTS:I/R led to multiple responses in mesenteric post-capillary venules,including a significant increase in the adhesion of leukocytes,production of oxygen radicals in the venular wall,albumin efflux and enhanced mast cell degranulation in vivo.All the I/R-induced manifestations were significantly reduced by pre-or post-treatment with TSA,with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA.Moreover,preor post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils,reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.CONCLUSION:The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R,which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils.

关键词： Salvia miltiorrhiza Leukocyte adherence Oxygen-free radicals Albumin leakage ischemiareperfusion

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Effect of intestinal ischemia-reperfusion on expressions of endogenous basic fibroblast growth factor and transforming growth factor β in lung and its relation with lung repair

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World Journal of Gastroenterology 2000年第3期6卷 353-355页

作者： Xiao Bing Fu Yin Hui Yang Tong Zhu Sun Xiao Man Gu Li Xian Jiang Xiao Oing Sun Zhi Yong Sheng Research Laboratory,304th Hospital of PLA,Beijing 100037,China 解放军第304医院北京

AIM To study the changes of endogenoustransforming growth factor β(TGFβ)and basicfibroblast growth factor(bFGF)in lung followingintestinal ischemia and reperfusion injury andtheir effects on lung injury and repair.METHODS Sixty Wistar rats were divided intofive groups,which underwent sham-operation,ischemia(45 minutes),and reperfusion(6,24and 48 hours,respectively)after ischemia(45minutes).Immunohistochemical method wasused to observe the localization and amounts ofboth growth factors.RESULTS Positive signals of both growthfactors could be found in normal lung,mainly inalveolar cells and endothelial cells of vein.Afterischemia and reperfusion insult,expressions ofboth growth factors were increased and theiramounts at 6 hours were larger than those ofnormal control or of 24 and 48 hours after insult.CONCLUSION The endogenous bFGF and TGF βexpression appears to be up-regulated in thelung following intestinal ischemia andreperfusion,suggesting that both growth factorsmay be involved in the process of lung injury andrepair.

关键词： lung intestinal ischemiareperfusion injury basic fibroblast growth factor transforming growth factor p

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