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BMC Nephrol ; 21(1): 206, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471386

RESUMO

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.


Assuntos
Proliferação de Células/efeitos dos fármacos , Rim/patologia , Nefrite/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Corantes de Rosanilina/uso terapêutico , Obstrução Ureteral/complicações , Actinas/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose/efeitos dos fármacos , Movimento Celular , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Colágeno Tipo IV/genética , Fibrose , Proteínas de Choque Térmico HSP47/metabolismo , Interleucina-1beta/genética , Rim/metabolismo , Túbulos Renais/patologia , Macrófagos/fisiologia , Masculino , Miofibroblastos/fisiologia , Nefrite/etiologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Corantes de Rosanilina/farmacologia , Fatores de Tempo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
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