دورية أكاديمية
Meta-Analysis of Preclinical Studies of Fibrinolytic Therapy for Acute Lung Injury.
العنوان: | Meta-Analysis of Preclinical Studies of Fibrinolytic Therapy for Acute Lung Injury. |
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المؤلفون: | Liu C; Institute of Lung and Molecular Therapy, Xinxiang Medical University, Xinxiang, China., Ma Y; Institute of Lung and Molecular Therapy, Xinxiang Medical University, Xinxiang, China., Su Z; Institute of Lung and Molecular Therapy, Xinxiang Medical University, Xinxiang, China., Zhao R; Department of Molecular and Cellular Biology, University of Texas Health Science Center at Tyler, Tyler, TX, United States., Zhao X; Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, United States., Nie HG; Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, China., Xu P; Institute of Lung and Molecular Therapy, Xinxiang Medical University, Xinxiang, China., Zhu L; School of Nursing, Xinxiang Medical University, Xinxiang, China., Zhang M; Institute of Lung and Molecular Therapy, Xinxiang Medical University, Xinxiang, China., Li X; Institute of Lung and Molecular Therapy, Xinxiang Medical University, Xinxiang, China., Zhang X; Department of Pulmonary Medicine, Henan Provincial People's Hospital, Zhengzhou, China., Matthay MA; Department of Anesthesia and Medicine, University of California, San Francisco, San Francisco, CA, United States., Ji HL; Department of Molecular and Cellular Biology, University of Texas Health Science Center at Tyler, Tyler, TX, United States. |
المصدر: | Frontiers in immunology [Front Immunol] 2018 Aug 20; Vol. 9, pp. 1898. Date of Electronic Publication: 2018 Aug 20 (Print Publication: 2018). |
نوع المنشور: | Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
مواضيع طبية MeSH: | Thrombolytic Therapy*, Acute Lung Injury/*drug therapy , Fibrinolytic Agents/*therapeutic use, Acute Lung Injury/etiology ; Acute Lung Injury/metabolism ; Acute Lung Injury/mortality ; Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Fibrinolytic Agents/pharmacology ; Humans ; Mice ; Mortality ; Neutrophils/immunology ; Neutrophils/metabolism ; Odds Ratio |
مستخلص: | Background: Acute lung injury (ALI) is characterized by suppressed fibrinolytic activity in bronchoalveolar lavage fluid (BALF) attributed to elevated plasminogen activator inhibitor-1 (PAI-1). Restoring pulmonary fibrinolysis by delivering tissue-type plasminogen activator (tPA), urokinase plasminogen activator (uPA), and plasmin could be a promising approach. Objectives: To systematically analyze the overall benefit of fibrinolytic therapy for ALI reported in preclinical studies. Methods: We searched PubMed, Embase, Web of Science, and CNKI Chinese databases, and analyzed data retrieved from 22 studies for the beneficial effects of fibrinolytics on animal models of ALI. Results: Both large and small animals were used with five routes for delivering tPA, uPA, and plasmin. Fibrinolytics significantly increased the fibrinolytic activity both in the plasma and BALF. Fibrin degradation products in BALF had a net increase of 408.41 ng/ml vs controls ( P < 0.00001). In addition, plasma thrombin-antithrombin complexes increased 1.59 ng/ml over controls ( P = 0.0001). In sharp contrast, PAI-1 level in BALF decreased 21.44 ng/ml compared with controls ( P < 0.00001). Arterial oxygen tension was improved by a net increase of 15.16 mmHg, while carbon dioxide pressure was significantly reduced (11.66 mmHg, P = 0.0001 vs controls). Additionally, fibrinolytics improved lung function and alleviated inflammation response: the lung wet/dry ratio was decreased 1.49 ( P < 0.0001 vs controls), lung injury score was reduced 1.83 ( P < 0.00001 vs controls), and BALF neutrophils were lesser (3 × 10 4 /ml, P < 0.00001 vs controls). The mortality decreased significantly within defined study periods (6 h to 30 days for mortality), as the risk ratio of death was 0.2-fold of controls ( P = 0.0008). Conclusion: We conclude that fibrinolytic therapy may be effective pharmaceutic strategy for ALI in animal models. |
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معلومات مُعتمدة: | R01 HL116826 United States HL NHLBI NIH HHS; R01 HL134828 United States HL NHLBI NIH HHS; R21 AI133465 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: fibrinolytic agents; interventions; lung diseases; molecular therapy; preclinical study |
المشرفين على المادة: | 0 (Fibrinolytic Agents) |
تواريخ الأحداث: | Date Created: 20180905 Date Completed: 20190930 Latest Revision: 20210109 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC6110197 |
DOI: | 10.3389/fimmu.2018.01898 |
PMID: | 30177934 |
قاعدة البيانات: | MEDLINE |
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