Interleukin-1 beta (IL-1 beta) Concentrations Assessed by Immunohistochemistry in the Commissural nTS and Hypoglossal Nuclei of Rats with E. Coli Peritonitis
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Authors: Martinez, B. V.; Clifford, C.; Campanaro, C.; Kola, G.; Tackett, S.; Horton, K.; Nethery, D. E.; Hsieh, Y.; Dick, T. E.; Jacono, F.
Abstract
Recombinant Extracellular Domain (p75ECD) of the Neurotrophin Receptor p75 Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting the p-JNK/Caspase-3 Signaling Pathway in Rat Microvascular Pericytes
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Authors: Fang, Jun; Wei, ZhiXiong; Zheng, DeDong; Ying, Teng; Hong, HuaShan; Hu, DanQing; Lin, YunLing; Jiang, XiaoLiang; Wu, LingZhen; Lan, TingXiang; Yang, ZhiWei; Zhou, XinFu; Chen, LiangLong
Abstract
BACKGROUND: Pro-NTs (precursor of neurotrophins) and their receptor p75 are potential targets for preventing microvascular dysfunction induced by myocardial ischemia-reperfusion injury (IRI). p75ECD (ectodomain of neurotrophin receptor p75) may physiologically produce neurocytoprotective effects by scavenging pro-NTs. We therefore hypothesized that p75ECD may have a cardioprotective effect on IRI through microvascular mechanisms. METHODS AND RESULTS: Myocardial IRI was induced in Sprague-Dawley rats by occluding the left main coronary arteries for 45 minutes before a subsequent relaxation. Compared with the ischemia-reperfusion group, an intravenous injection of p75ECD (3 mg/kg) 5 minutes before reperfusion reduced the myocardial infarct area at 24 hours after reperfusion (by triphenyltetrazolium chloride, 44.9+3.9% versus 34.6+5.7%, P<0.05); improved the left ventricular ejection fraction (by echocardiography), with less myocardial fibrosis (by Masson's staining), and prevented microvascular dysfunction (by immunofluorescence) at 28 days after reperfusion; and reduced myocardial pro-NTs expression at 24 hours and 28 days after reperfusion (by Western blotting). A simulative IRI model using rat microvascular pericytes was established in vitro by hypoxia-reoxygenation (2/6 hours) combined with pro-NTs treatment (3 nmol/L) at R. p75ECD (3 pg/mL) given at R improved pericyte survival (by methyl thiazolyl tetrazolium assay) and attenuated apoptosis (by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling). In the reperfused hearts and hypoxia-reoxygenation +pro-NTs-injured pericytes, p75ECD inhibited the expression of p-JNK (phospho of c-Jun N-terminal kinase)/caspase-3 (by Western blotting). SP600125, an inhibitor of JNK, did not enhance the p75ECD-induced infarct-sparing effects and pericyte protection. CONCLUSIONS: p75ECD may attenuate myocardial IRI via pro-NTs reduction-induced inhibition of p-JNK/caspase-3 pathway of microvascular pericytes in rats.
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