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Investigation into statins as prevention and treatment of inflammation in pregnancy

他汀类药物预防和治疗妊娠期炎症的研究

基本信息

批准号：
9975203
负责人：
Egle Bytautiene Prewit
金额：
$ 8.02万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-10 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975203
关键词：
Accounting Alveolar Animal Model Anti-Inflammatory Agents Antiinflammatory Effect Birth Brain Bronchopulmonary Dysplasia CASP3 gene Cerebral Palsy Coenzyme A Cyclic AMP-Dependent Protein Kinases Cyclic GMP-Dependent Protein Kinases Cyclic Nucleotides Effectiveness Encephalitis Epidemiology Etiology Exposure to Female Fetal Tissues Gastrointestinal tract structure Gene Expression Genetic Transcription Goals Goblet Cells IL8 gene Incubated Inflammation Inflammatory Inflammatory Response Injections Injury Interleukin-1 beta Interleukin-10 Interleukin-4 Interleukin-6 Intestines Investigation Lipopolysaccharides Lung MAP Kinase Gene MAPK8 gene Measures Mediating Microtubules Mitogens Modeling Mus Myelin Basic Proteins Necrotizing Enterocolitis Neonatal Neonatal respiratory morbidity Neuraxis Neurologic Outcome Oxidoreductase Paneth Cells Pathway interactions Periventricular Leukomalacia Phosphotransferases Pravastatin Pregnancy Premature Birth Premature Labor Prevention Property Protein Kinase C Proteins Regulation Reporting Rho-associated kinase Role Secondary to Simvastatin Soluble Guanylate Cyclase TNF gene Testing Therapeutic Tissues Transcription Factor AP-1 Up-Regulation Vascular Endothelial Growth Factors body system clinically significant congenital anomaly cytokine design experimental study farnesyl pyrophosphate fetal fetal brain injury gastrointestinal system gender difference geranylgeranyl pyrophosphate hydrophilicity infant death inflammatory marker inhibitor/antagonist intraperitoneal intraventricular hemorrhage lipophilicity male mortality mouse model neonatal outcome p38 Mitogen Activated Protein Kinase phosphoric diester hydrolase pregnant premature prenatal preterm premature rupture of membranes prevent primary outcome protein kinase inhibitor pup respiratory distress syndrome response secondary outcome therapy development transcription factor

项目摘要

ABSTRACT Prematurity remains a leading cause of short- and long-term neonatal morbidity of the respiratory (respiratory distress syndrome, bronchopulmonary dysplasia), central nervous (intraventricular hemorrhage, periventricular leukomalacia, cerebral palsy), and gastrointestinal systems (necrotizing enterocolitis), as well as mortality. Leading mechanisms for the PTB spectrum and its related adverse neonatal outcomes are exaggerated maternal and fetal/neonatal inflammation, secondary to infectious or noninfectious etiologies Our central hypothesis is that prenatal administration of statins abolishes the inflammatory responses in fetal tissues by increasing the hemoxygenase-1 expression in a murine model of LPS-induced systemic maternal inflammation. The proposed hypothesis will be investigated in an established animal model, in which pregnant mice are treated with either a lipophilic (simvastatin) or hydrophilic (pravastatin) statin with and without HO-1 inhibitor before or after intra-peritoneal administration of LPS. These studies are clinically significant as they will 1) determine gender differences in response to maternal inflammation and statin treatment, 2) determine HO-1’s role in preventing fetal/neonatal inflammatory injury by statins, and 3) establish the effectiveness of lipophilic versus hydrophilic statins in preventing fetal inflammatory response to maternal systemic inflammation. Successful testing of aims will introduce new paradigms for development of therapies to prevent fetal complications of preterm birth.

摘要