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BMC Nephrol ; 21(1): 206, 2020 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-32471386

RESUMEN

BACKGROUND: Previous study showed that purinergic P2X7 receptors (P2X7R) reach the highest expression in the first week after unilateral ureteral obstruction (UUO) in mice, and are involved in the process of inflammation, apoptosis and fibrosis of renal tissue. We, herein, document the role of purinergic P2X7 receptors activation on the third day of UUO, as assessed by means of BBG as its selective inhibitor. METHODS: We investigated the effects of brilliant blue G (BBG), a P2X7R antagonist, in the third day of kidney tissue response to UUO in rats. For this purpose, male Wistar rats submitted to UUO or sham operated, received BBG or vehicle (V), comprising four groups: UUO-BBG, UUO-V, sham-BBG and sham-V. The kidneys were harvested on day 3 UUO and prepared for histology, immunohistochemistry (P2X7R, PCNA, CD-68, α-sma, TGF-ß1, Heat-shock protein-47, TUNEL assay), quantitative real-time PCR (IL-1ß, procollagens type I, III, and IV) for mRNA quantification. RESULTS: The group UUO-V presented an enhancement in tubular cell P2X7-R expression, increase influx of macrophages and myofibroblasts, HSP-47 and TGF- ß1 expression. Also, upregulation of procollagen types I, III, and IV, and IL-1ß mRNAs were seen. On the other hand, group UUO-BBG showed lower expression of procollagens and IL-1ß mRNAs, as well as less immunoreactivity of HSP-47, TGF-ß, macrophages, myofibroblasts, and tubular apoptosis. This group also presented increased epithelial cell proliferation. CONCLUSION: BBG, a known highly selective inhibitor of P2X7R, attenuated renal inflammation, collagen synthesis, renal cell apoptosis, and enhanced renal cell proliferation in the early phase of rat model of UUO.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Riñón/patología , Nefritis/tratamiento farmacológico , Antagonistas del Receptor Purinérgico P2X/uso terapéutico , Colorantes de Rosanilina/uso terapéutico , Obstrucción Ureteral/complicaciones , Actinas/metabolismo , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Apoptosis/efectos de los fármacos , Movimiento Celular , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Colágeno Tipo IV/genética , Fibrosis , Proteínas del Choque Térmico HSP47/metabolismo , Interleucina-1beta/genética , Riñón/metabolismo , Túbulos Renales/patología , Macrófagos/fisiología , Masculino , Miofibroblastos/fisiología , Nefritis/etiología , Antagonistas del Receptor Purinérgico P2X/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Colorantes de Rosanilina/farmacología , Factores de Tiempo , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba
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