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1.
J Cell Mol Med ; 22(2): 808-822, 2018 02.
Article in English | MEDLINE | ID: mdl-29063670

ABSTRACT

Emerging evidence indicates that irisin provides beneficial effects in diabetes. However, whether irisin influences the development of diabetic cardiomyopathy (DCM) remains unclear. Therefore, we investigated the potential role and mechanism of action of irisin in diabetes-induced myocardial dysfunction in mice. Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic mice were administered recombinant r-irisin (low or high dose: 0.5 or 1.5 µg/g body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood glucose levels in the diabetic mice. However, the results of echocardiographical and histopathological assays indicated that low-dose irisin treatment alleviated cardiac fibrosis and left ventricular function in the diabetic mice, whereas high-dose irisin failed to mitigate the ventricular function impairment and increased collagen deposition. The potential mechanism underlying the effect of low-dose irisin involved irisin-mediated inhibition of high glucose-induced endothelial-to-mesenchymal transition (EndMT); conversely, high-dose irisin treatment enhanced high glucose-induced MMP expression by stimulating MAPK (p38 and ERK) signalling and cardiac fibroblast proliferation and migration. Low-dose irisin alleviated DCM development by inhibiting high glucose-induced EndMT. By contrast, high-dose irisin disrupted normal MMP expression and induced cardiac fibroblast proliferation and migration, which results in excess collagen deposition. Thus, irisin can inhibit high glucose-induced EndMT and exert a dose-dependent bidirectional effect on DCM.


Subject(s)
Diabetic Cardiomyopathies/pathology , Fibronectins/pharmacology , Glucose/toxicity , Human Umbilical Vein Endothelial Cells/pathology , Mesoderm/pathology , Animals , Blood Glucose/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Collagen/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Cardiomyopathies/blood , Diabetic Cardiomyopathies/physiopathology , Enzyme Activation/drug effects , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Fibrosis , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mesoderm/drug effects , Mice, Inbred C57BL , Myocardium/metabolism , Myocardium/pathology , Phosphorylation/drug effects , Signal Transduction/drug effects , Smad Proteins/metabolism , Streptozocin , Transforming Growth Factor beta/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
2.
Zhonghua Er Bi Yan Hou Ke Za Zhi ; 38(2): 118-20, 2003 Apr.
Article in Chinese | MEDLINE | ID: mdl-12889110

ABSTRACT

OBJECTIVES: To study applying auditory brainstem reaction (ABR) to monitor the general anesthesia depth and awaken degree in children as an objective guide. METHODS: Forty-five infant or children patients, American Society of Anesthesiologists(ASA) graded I-II, with normal audition, were selected and divided into 3 groups (15 cases per group) to receive propofal venous anesthesia, fentanyl venous anesthesia, or isoflurane anesthesia, respectively. During anesthesia, peak latencies (PL) of I, III, V wave, and interpeak latencies (IPL) of I-III, III-V, I-V were monitored and recorded after short sound stimulation of 90 db which accumulated 1,000 times with Madsen. The changing of PL and IPL with time passing and anesthesia dosage was studied to discuss the feature of ABR in each anesthesia procedure as above. RESULTS: There is a significant positive correlation between PL and IPL of ABR waves as above and the dosage of propofol or the concentration of isoflurane. The dosage or the concentration increased, and PL and IPL prolonged. It is important of PL of wave I to reflect anesthesia degree. It is wave V with the best stability and correlation to monitor anesthesia degree. After anesthesia period or patients almost awaken, PL and IPL of some ABR waves were still more than normal values, which is detention reaction. For the fentanyl anesthesia, ABR is not sensible enough, i.e. has little correlation. CONCLUSION: The changing of PL and IPL of ABR waves could conclude anesthesia degree in children and be treated as reference of whether awaken or not in some certain, but have possibility of detention reaction.


Subject(s)
Anesthesia Recovery Period , Anesthesia, General , Evoked Potentials, Auditory, Brain Stem , Anesthetics, Intravenous , Child , Child, Preschool , Female , Fentanyl , Humans , Infant , Male , Monitoring, Intraoperative , Propofol
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