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雷米普利对心肌梗死后心脏血管紧张素受体基因转录的影响(英文)

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中国药理学报 1999年第6期20卷 481-485页

作者：朱依纯朱依谆李军 HeinerSCHAFER Wolfgang ESCHMIDT thomas unger 姚泰上海医科大学生理学教研室 Department of Pharmacology University of Kiel DepartmentofInternalMedicineUniversityHospitalofKiel Department of InternalMedicineUniversityHospital of Kiel Kiel24105Germany

在慢性给予血管紧张素转换酶抑制剂雷米普利后的大鼠中观察心肌梗死（ＭＩ）后早期心肌组织中血管紧张素 Ⅱ（Ａｕｇ Ⅱ）受体基因转录的改变．方法：通过冠状动脉结扎建立大鼠ＭＩ模型，手术前１周即开始给予雷米普利或水，术后在存... 详细信息

在慢性给予血管紧张素转换酶抑制剂雷米普利后的大鼠中观察心肌梗死（ＭＩ）后早期心肌组织中血管紧张素 Ⅱ（Ａｕｇ Ⅱ）受体基因转录的改变．方法：通过冠状动脉结扎建立大鼠ＭＩ模型，手术前１周即开始给予雷米普利或水，术后在存活大鼠中继续治疗至处死大鼠；用定量ＲＴ－ＰＣＲ法检测大鼠心间隔组织的Ａｎｇ Ⅱ受体ｍＲＮＡ水平．结果：大鼠ＭＩ后心间隔组织中ＡＴ１和ＡＴ２受体ｍＲＮＡ水平升高，在１ｄ时达到高峰．给予雷米普利的大鼠ＭＩ后心间隔组织中Ａｎｇ Ⅱ受体ＩｎＲＮＡ水平与给予水的大鼠相比无显著差别．结论：非梗死区心肌组织中Ａｎｇ Ⅱ受体基因转录的特征性改变可能与ＭＩ后心肌重构过程有关而与ＡＣＥ抑制无关．

关键词：心肌梗塞血管紧张素Ⅱ 受体雷米普利基因转录

Effects of endothelin ETA receptor blocker LU 135252 on cardiac remod-eling and survival in a hypertensive rat model of chronic heart failure

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Acta Pharmacologica Sinica 2006年第11期27卷 1417-1422页

作者： Alexander REINECKE Marc DORENKAMP Mat Jap DAEMEN Reichiger SIMON thomas unger Clinic of Cardiology Christian-Albrechts-University of Kiel24105 KielGermany Institute of Pharmacology Christian-Albrechts University of Kiel24105 KielGermany Department of Pathology University of MaastrichtMaastrichtthe Netherlands

Aim:To investigate whether the endothelin ETAreceptor blocker provides similarbenefit on cardiac remodeling and survival in a hypertensive rat model of chronicheart failure（CHF）.Methods:Male stroke-prone spontaneously hypertensive（SHR-SP）rats were subjected to permanent ligation of the left coronary artery andwere treated for 6 weeks with the endothelin ETAreceptor blocker LU 135252(***-1.d-1)starting 24 h after ligation or ***-operated rats servedas normal *** mean arterial blood pressure（MAP）,heart rate（HR）,leftventricular end-diastolic pressure（LVEDP）,left ventricular contractility(LVdp/dtmax),left ventricular inner diameter（LVD）and circumference（LVC）,septalthickness,left ventricular interstitial collagen content（ICC）and heart weight（HW）were measured at the end of the ***:Compared with the untreatedgroup,LU 135252 tended to increase HW（1.43±0.03 vs 1.38±0.04 g;P>0.05）,increased LVD（7.65±0.24 mm vs 6.58±0.14 mm;P0.05）,reduced LVEDP（144mmHg vs 27±4 mmHg;P<0.05）andimproved LV dp/dtmax（4230±450 mmHg/s vs 1950±400 mmHg/s;P<0.05）;survivalwas not prolonged significantly（13% vs 11%;P=NS）.Conclusion:In this hyper-tensive rat model of CHF,chronic endothelin ETA receptor blockade with LU 135252improves cardiac hemodynamics,however,it does not affect long-term survivaland worsens cardiac ***,endothelin ETAreceptor antagonists areunlikely to have an important role in the management of patients with CHF.

关键词： myocardial infarction heart failure endothelin ET_A receptor antagonism LU 135252 cardiac remodeling ventricular function SHR-SP rats

Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone spontaneously hypertensive rats

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Acta Pharmacologica Sinica 2004年第6期 61-66页

作者： Alexander REINECKE,Marc DORENKAMP,Christain STORZ,Havvo BITTERLING,Susanne PENZ,Jack CLEUTJENS,Mat JAP DAEMEN,Reichiger SIMON,thomas unger Institute of Pharmacology University of Kiel 24105 Kiel Germany Institute of Pharmacology University of Kiel 24105 Kiel Germany Clinic of Cardiology Institute of Pharmacology University of Kiel 24105 Kiel Germany Institute of Pharmacology University of Kiel 24105 Kiel Germany University of Kiel Department of Pathology University ofMaastricht Maastricht The Netherlands Clinic of Cardiology University of Kiel 24105 Kiel Germany 24105 Kiel Institute of Pharmacology University of Kiel 24105 Kiel Germany Germany Institute of Pharmacology University of Kiel 24105 Kiel Germany

AIM: To elucidate the cardioprotective effects of T-type calcium channel blocker mibefradil and compare with that of the angiotensin-converting enzyme inhibitor ramipril in a stroke-prone spontaneously hypertensive rats (SHR- SP) model of congestive heart failure (CHF) after myocardial infarction (MI). METHODS: SHR-SP rats were subjected to permanent ligation of the left anterior decending coronary artery. Treatment with mibefradil (10 mg·kg-1·d-1), ramipril (10 mg·kg-1·d-1), or placebo was initiated 4 weeks before surgery and continued up to 6 weeks after induction of MI. Sham-operated rats served as controls. RESULTS: In placebo-treated MI rats, six weeks after MI, left ventricular circumference, inner diameter, and left ventricular end-diastolic pressure (LVEDP) were increased, whereas mean arterial blood pressure (MAP) and maximum rate of rise of left ventricular pressure (dp/ dtmax) were decreased compared with sham-operated controls (P05), and dp/dtmax was improved (P<0.01) compared with placebo-treated MI rats. In contrast, in mibefradil-treated MI rats, heart weight, heart weight to body weight ratio were slightly but not signifi- cantly reduced, LVEDP was slightly elevated compared with placebo-treated MI rats, and was elevated (P<0.05) compared with ramipril-treated MI rats, although interstitial collagen content were reduced (P<0.01) compared with placebo-treated MI ***: Chronic treatment with ramipril diminishes cardiac remodeling of heart failure after MI to a greater extent than mibefradil. Moreover, 6 weeks after MI, mibefradil treatment results in a slight rise in LVEDP compared with placebo-treated rats. Therefore, treatment with mibefradil might be deleterious rather than beneficial compared with ramipril or even placebo treatment in experim

关键词： mibefradil ramipril angiotensin-converting enzyme inhibitors calcium channel blockers myocar- dial infarction heart failure cardiac remodeling ventricular function SHR-SP rats

LONG-TERM INHIBITION OF Na~+/H~+ EXCHANGE ATTENUATES CARDIAC REMODELING AFTER MYOCARDIAL INFARCTION IN RATS

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2001年第4期 80-85页

作者： XIA Qin-gui\+*L, Oliver Chung, Heidi Spitznagel, thomas unger (Institute of Pharmacology, Christian-Albrechts-University of Kiel, Hospitalstrasse 4, 24105 Kiel, Germany)\%

Objective: In addition to pH regulation, Na\++/H\++ exchanger (NHE) has been shown to facilitate cell growth and proliferation. However, the effects of long-term inhibition of Na\++/H\++ exchange on cardiac structural and functional remodeling post myocardial infarction (MI) are still controversial. The present study was therefore carried out to further investigate the effects of long-term treatment with cariporide, a specific inhibitor of NHE-1, on cardiac remodeling after MI in rats; Methods: Male Wistar rats that underwent coronary ligation were randomly selected for cariporide treatment starting 6 h after induction of MI or no *** was continued up to 6 weeks post MI, after which, the arterial, venous and left ventricular catheters were chronically implanted. Twenty-four h later, after hemodynamic signals were recorded in conscious rats, they were sacrificed and hearts were taken out for morphological examinations; Results: Cariporide treatment decreased the heart weight and heart weight to body weight ratio (both \%P\%<0.05), decreased left ventricular end-diastolic pressure (\%P\%<0.001), improved myocardial contractility (d\%P\%/d\%t\%\-\{max\}) (\%P\%<0.05) and tended to increase the survival of treated rats compared to that of untreated infarct rats; Conclusion: The results of the present study indicate that the long-term inhibition of NHE with cariporide can attenuate cardiac structural remodeling and improve left ventricular dysfunction in infarcted rats, and suggest that Na\++/H\++ exchange inhibition could be an effective therapeutic strategy for myocardial infarction-induced heart failure.

关键词： myocardial infarction Na\++/H\++ exchange inhibitor remodeling ventricular function

Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 199-200页

作者： Srishti Chawla Mikael Molin thomas Nystrom Institute for Biomedicine Sahlgrenska AcademyCentre for Ageing and Health-AgeCapUniversity of GothenburgGothenburgSweden Department of Life Sciences Chalmers University of TechnologyGothenburgSweden

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and *** biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated *** is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate *** calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

关键词： activation dinuclear conserved

Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng thomas Skutella Karl Kiening Andreas Unterberg Alexander Younsi Department of Neurosurgery Heidelberg University HospitalHeidelbergGermany Department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease

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World Journal of Gastroenterology 2021年第19期27卷 2281-2298页

作者： Lukas Hartl Joshua Elias Gerhard Prager thomas Reiberger Lukas W unger Division of Gastroenterology and Hepatology Department of Internal Medicine IIIMedical University of ViennaVienna A-1090Austria Vienna Hepatic Hemodynamic Lab Medical University of ViennaVienna A-1090Austria Cambridge Institute of Therapeutic Immunology and Infectious Disease Jeffrey Cheah Biomedical CentreUniversity of CambridgeCambridge CB20AWUnited Kingdom Division of Gastroenterology and Hepatology Department of MedicineUniversity of CambridgeAddenbrooke’s HospitalCambridge CB20QQUnited Kingdom Division of Visceral Surgery Department of General SurgeryMedical University of ViennaVienna A-1090Austria

The obesity pandemic has led to a significant increase in patients with metabolic dysfunction-associated fatty liver disease(MAFLD).While dyslipidemia,type 2 diabetes mellitus and cardiovascular diseases guide treatment in patients without signs of liver fibrosis,liver related morbidity and mortality becomes relevant for MAFLD’s progressive form,non-alcoholic steatohepatitis(NASH),and upon development of liver *** should be prescribed in patients without significant fibrosis despite concomitant liver diseases but are underutilized in the real-world *** surgery,especially Y-Roux bypass,has been proven to be superior to conservative and/or medical treatment for weight loss and resolution of obesity-associated diseases,but comes at a low but existent risk of surgical complications,reoperations and very rarely,paradoxical progression of *** end-stage liver disease develops,obese patients benefit from liver transplantation(LT),but may be at increased risk of perioperative infectious *** LT,metabolic comorbidities are commonly observed,irrespective of the underlying liver disease,but MAFLD/NASH patients are at even higher risk of disease *** studies with low patient numbers evaluated if,and when,bariatric surgery may be an option to avoid disease recurrence but more high-quality studies are needed to establish clear *** this review,we summarize the most recent literature on treatment options for MAFLD and NASH and highlight important considerations to tailor therapy to individual patient’s needs in light of their risk profile.

关键词： Metabolic dysfunction-associated fatty liver disease Non-alcoholic fatty liver disease Portal hypertension Cirrhosis Bariatric surgery Metabolism

Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis

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World Journal of Hepatology 2021年第7期13卷 731-746页

作者： Nikolaus Pfisterer Lukas W unger thomas Reiberger Medizinische Abteilung für Gastroenterologie und Hepatologie Klinik Landstraße/Krankenanstalt RudolfstiftungVienna 1030Austria Vienna Hepatic Hemodynamic Lab Medical University of ViennaVienna 1090Austria Division of Visceral Surgery Department of General SurgeryMedical University of ViennaVienna 1090Austria Cambridge Institute of Therapeutic Immunology and Infectious Disease Jeffrey Cheah Biomedical CentreUniversity of CambridgeCambridge CB20AWUnited Kingdom Division of Gastroenterology and Hepatology Department of Medicine IIIMedical University of ViennaVienna 1090Austria Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis Medical University of ViennaVienna 1090Austria

Portal hypertension(PH),a common complication of liver cirrhosis,results in development of esophageal *** esophageal varices rupture,they cause significant upper gastrointestinal bleeding with mortality rates up to 20%despite state-of-the-art ***,prophylactic measures are of utmost importance to improve outcomes of patients with *** high-quality studies have demonstrated that non-selective beta blockers(NSBBs)or endoscopic band ligation(EBL)are effective for primary prophylaxis of variceal *** secondary prophylaxis,a combination of NSBB+EBL should be routinely *** esophageal varices develop and variceal bleeding occurs,standardized treatment algorithms should be followed to minimize bleeding-associated *** attention should be paid to avoidance of overtransfusion,early initiation of vasoconstrictive therapy,prophylactic antibiotics and early endoscopic ***-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding,and potentially in Child B patients with active bleeding at *** use of carvedilol,safety of NSBBs in advanced cirrhosis(*** refractory ascites)and assessment of hepatic venous pressure gradient response to NSBB is *** the present review,we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.

关键词： Portal hypertension Endoscopy Non-selective betablockers Transjugular intrahepatic portosystemic shunt

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis