ABSTRACT
Aim To investigate whether notoginsenoside Rl (PNS-R1) alleviates allergic rhinitis (AR) through AMP-activated protein kinase (AMPK)/mitochondrial fission critical protein (DRP1) -mediated mitochondrial fission. Methods Different doses of PNSRl were used to treat ovalbumin (OVA) -induced AR model mice,and the inhibitory effect of PNS-R1 on AR was investigated by observing allergic symptoms such as nasal rubbing and sneezing, as well as HE staining of nasal tissues. Serum IgE levels and nasal lavage fluid (NLF) inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA) and apoptosis-related proteins were detected by Western blot. In vitro human nasal epithelial cells (HNEpC) were stimulated with IL-13 to observe apoptosis, mitochondrial membrane potential, cellular ROS and mitochondrial ROS production, as well as the expression levels of AMPK/DRP1, expression levels of the TXNIP/NLRP3 inflammasomes and the translocation of DRP1. Results PNS-R1 attenuated allergic symptoms in AR mice, HE staining reduced inflammatory cells and reduced the levels of OVA-specific IgE in serum, and the levels of IL-4, IL-6, and IL-8 in NLF. PNS-R1 attenuated the apoptosis and ROS production of nasal epithelial cells in AR. In vitro PNS-R1 could up-regulate mitochondrial membrane potential after IL-13 stimulation, reduce ROS and mtROS production, the proportion of apoptotic positive cells, and reduce cleaved caspase-3, Bax, and up-regulate Bcl-2 expression, down-regulate DRP1 phosphorylation (Ser 616) and DRP1 translocation at the mitochondrial membrane in an AMPK-dependent manner, reducing TXNIP/NLRP3 expression. Conclusions PNS-R1 can protect mitochondrial integrity by inhibiting the AMPK/DRP1 signaling axis and its subsequent TXNIP/NLRP3 signaling axis,thereby alleviating rhinitis in AR mice.
ABSTRACT
Abstract This article seeks to understand the circumstances that culminated in the formulation and implementation of the National Rural Water Supply and Sanitation Project (PNSR) in the 1980s, using the Multiple Streams Model as its theoretical reference. The results show that the theme's ascension to the government agenda stemmed from a conjuncture marked by intense transitions that contributed to opening a policy window. The struggle to guarantee social rights in the Brazilian re-democratization process; the activities of social movements like the grassroots public health movement; the large sanitary deficit and its consequences for public health; the joint involvement of institutions with considerable expertise like Economic and Social Planning Institute (IPEA), Public Health Special Service Foundation (FSESP) and Pan-American Health Organization (PAHO) and the availability of financial resources stemming from a partnership arrangement with the International Bank for Reconstruction and Development (IBRD) provided a favorable environment for the elaboration of the PNSR.
Resumen Este documento tiene como objetivo comprender las circunstancias que condujeron a la formulación e implementación, en la década de 1980, del Proyecto Nacional de Abastecimiento de Agua y Saneamiento Rural (PNSR), adoptando como marco teórico el modelo de flujos múltiples. Los resultados muestran que su ascenso a la agenda del gobierno se debe a una coyuntura marcada por intensas transiciones, que contribuyeron a la apertura de una ventana de oportunidad. La búsqueda de la garantía de los derechos sociales en el proceso de redemocratización brasileña; el desempeño de movimientos sociales, como el movimiento sanitario; el gran déficit de saneamiento y sus consecuencias en la salud pública; la participación conjunta de instituciones con experiencia, como el Instituto de Planificación Económica y Social (IPEA), la Fundación del Servicio Especial de Salud Pública (FSESP) y la Organización Panamericana de la Salud (OPS), y la disponibilidad de recursos financieros de una asociación con el Banco Internacional de Reconstrucción y Fomento (BIRF) proporcionó un entorno favorable para la elaboración del PNSR.
Resumo O presente artigo busca compreender as circunstâncias que culminaram na formulação e implementação, na década de 1980, do Projeto Nacional de Saneamento Rural (PNSR), adotando como marco teórico o Modelo de Múltiplos Fluxos. Os resultados evidenciam que sua ascensão à agenda governamental é decorrente de uma conjuntura marcada por intensas transições, que contribuíram para a abertura de uma janela de oportunidades. A busca pela garantia de direitos sociais no processo de redemocratização brasileiro; a atuação de movimentos sociais, como o movimento sanitarista; o grande déficit sanitário e suas consequências na saúde pública; o envolvimento conjunto de instituições com expertise, como o Instituto de Planejamento Econômico e Social (IPEA), a Fundação Serviço Especial de Saúde Pública (FSESP) e a Organização Pan-Americana de Saúde (OPAS) e a disponibilidade de recursos financeiros, provenientes de parceria com o Banco Internacional para Reconstrução e Desenvolvimento (BIRD), proporcionaram um ambiente favorável para a elaboração do PNSR.