RESUMEN
OBJECTIVES: To investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury. DESIGN: Experimental study. SETTING: Research laboratory. SUBJECTS: Patients with acute respiratory distress syndrome and control subjects, wild-type C57BL/6 and formyl peptide receptor-1 gene knockout mice, and primary rat alveolar epithelial type II cells. INTERVENTIONS: Samples of bronchoalveolar lavage fluid and serum were obtained from patients and control subjects. Mice were intratracheally instilled with lipopolysaccharide and mitochondrial damage-associated molecular patterns. The primary rat alveolar epithelial type II cells were isolated and incubated with mitochondrial damage-associated molecular patterns. MEASUREMENTS AND MAIN RESULTS: Patients were divided into direct (pulmonary) and indirect (extrapulmonary) injury groups based on etiology. The release of mitochondrial peptide nicotinamide adenine dinucleotide dehydrogenase 1 in both bronchoalveolar lavage fluid and serum was induced in patients and was associated with etiology. In the lipopolysaccharide-induced lung injury, administration of mitochondrial damage-associated molecular patterns exacerbated the lung fluid imbalance, which was mitigated in formyl peptide receptor-1 knockout mice. Proteomic analysis of mouse lung tissues revealed the involvement of ion channels and tight junction proteins in this process. Treatment with mitochondrial damage-associated molecular patterns decreased the expression of epithelial sodium channel α, zonula occludens-1, and occludin via the formyl peptide receptor-1/p38 pathway in the primary rat alveolar epithelial type II cells. CONCLUSIONS: Mitochondrial damage-associated molecular patterns exacerbate lung fluid imbalance in the experimental acute lung injury model through formyl peptide receptor-1 signaling, the inhibition of which may prevent exacerbation of lung fluid imbalance induced by mitochondrial damage-associated molecular patterns. Thus, formyl peptide receptor-1 is a potential therapeutic target for acute respiratory distress syndrome.
Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Pulmón/metabolismo , Mitocondrias/metabolismo , Receptores de Formil Péptido/metabolismo , Transducción de Señal , Lesión Pulmonar Aguda/patología , Animales , Líquido del Lavado Bronquioalveolar/química , Complejo I de Transporte de Electrón/metabolismo , Humanos , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratas , Síndrome de Dificultad Respiratoria/metabolismo , Mucosa Respiratoria/metabolismoRESUMEN
OBJECTIVE: To evaluate the diagnostic value of ultrasound parameters of ovarian stroma area (S), total ovarian area (A) and S/A ratio for polycystic ovarian syndrome (PCOS). METHODS: The A, S and S/A ratio were determined by use of transvaginal pelvic ultrasound, and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) were assayed in 58 PCOS patients and 60 controls. Of 58 PCOS patients, 32 underwent hyperinsulinemic euglycemic clamp technique (HGCT). RESULTS: Patients with PCOS showed significantly higher ovarian S and S/A ratio when compared to the control groups (P = 0.045, P = 0.001, respectively). S/A ratio and S were significantly related to HGCT results and T. CONCLUSION: The S/A ratio and S are of value in diagnosis of PCOS.