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Lipid nanoparticle-encapsulated lncRNA DLX6-AS1 knockdown ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.
Song, Chang; Li, Yan; Han, Huiying; Zhang, Yueyue; Wang, Ning.
Afiliación
  • Song C; Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • Li Y; Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • Han H; Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • Zhang Y; Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • Wang N; Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Neurol Res ; 46(8): 706-716, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38735062
ABSTRACT

OBJECTIVE:

Cerebral ischemia is a neurological disorder that leads to permanent disability. This research focuses on exploring the ameliorative effects of lipid nanoparticle (LNP)-encapsulated lncRNA DLX6-AS1 knockdown in cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.

METHODS:

LNP-encapsulated lncRNA DLX6-AS1 was prepared. Cerebral ischemic injury mouse models were established utilizing middle cerebral artery occlusion (MCAO). The mice were treated by intravenous injection of LNP-encapsulated lncRNA DLX6-AS1. The neurological deficits, Inflammatory factor levels, pathological characteristics were observed. In vitro N2a cell oxygen and glucose deprivation (OGD) models were established, and the cells were treated with LNP-encapsulated lncRNA DLX6-AS1 or Nrf2 inhibitor (ML385). Cell viability and apoptosis were tested. DLX6-AS1, Nrf2, HO-1, and NLRP3 expression levels were assessed.

RESULTS:

LncRNA DLX6-AS1 levels were elevated in the brain tissues of mice with cerebral ischemic injury and OGD-induced N2a cells. LNP-encapsulated DLX6-AS1 siRNA (si-DLX6-AS1) improved neurological deficit scores, reduced the levels of inflammatory factors, improved brain tissue pathological damage, and raised the number of survival neurons in CA1. LNP-encapsulated si-DLX6-AS1 ameliorated the OGD-induced N2a cell viability decrease and apoptosis rate increase, and ML385 (Nrf2 inhibitor) reversed the ameliorative effects of LNP-encapsulated si-DLX6-AS1. In cerebral ischemic injury mice and OGD-induced N2a cells, Nrf2 and HO-1 levels were reduced and NLRP3 levels were increased. LNP-encapsulated si-DLX6-AS1 raised Nrf2 and HO-1 levels and reduced NLRP3 levels. Nrf2 inhibitor ML385 treatment reversed the ameliorative effects of LNP-encapsulated si-DLX6-AS1 on OGD-induced N2a cell viability and apoptosis.

CONCLUSION:

Lipid nanoparticle-encapsulated si-DLX6-AS1 ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Isquemia Encefálica / Factor 2 Relacionado con NF-E2 / Nanopartículas / ARN Largo no Codificante / Proteína con Dominio Pirina 3 de la Familia NLR Límite: Animals Idioma: En Revista: Neurol Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Isquemia Encefálica / Factor 2 Relacionado con NF-E2 / Nanopartículas / ARN Largo no Codificante / Proteína con Dominio Pirina 3 de la Familia NLR Límite: Animals Idioma: En Revista: Neurol Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido