RESUMO
Persistent inflammation disrupts functional recovery after spinal cord injury (SCI). Peroxisome proliferator-activated receptor gamma (PPAR-γ) activation promotes functional recovery in SCI rats by inhibiting inflammatory cascades and increasing neuronal survival. We sought to clarify the relationship between PPAR-γ activation and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome suppression, and the role of NF-κB in activating the NLRP3 inflammasome in neurons. In SCI rats, we found that rosiglitazone (PPAR-γ agonist) inhibited the expression of caspase-1. In in vitro neurons, G3335 (PPAR-γ antagonist) reversed the rosiglitazone-induced inhibition of caspase-1, interleukin 1 (IL-1ß), and interleukin 6 (IL-6). Rosiglitazone inhibited the expression of NLRP3, caspase-1, IL-1ß, and IL-6. However, the activator of NLRP3 could counteract this inhibition induced by PPAR-γ activation. NF-κB did not participate in the process of rosiglitazone-induced inhibition of NLRP3. Consistent with our in vitro results, we verified that locomotor recovery of SCI rats in vivo was regulated via PPAR-γ, NLRP3, and NF-κB. These results suggest that PPAR-γ activation exerts an anti-inflammatory effect by suppressing the NLRP3 inflammasome-but not NF-κB-in neurons and that PPAR-γ activation is a promising therapeutic target for SCI.
Assuntos
Anti-Inflamatórios/uso terapêutico , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PPAR gama/metabolismo , Animais , Caspase 1/metabolismo , Feminino , Imuno-Histoquímica , Inflamação/metabolismo , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Rosiglitazona/uso terapêutico , Medula Espinal/citologia , Medula Espinal/metabolismoRESUMO
The peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist rosiglitazone inhibits NF-κB expression and endogenous neural stem cell differentiation into neurons and reduces the inflammatory cascade after spinal cord injury (SCI). The aim of this study was to explore the mechanisms underlying rosiglitazone-mediated neuroprotective effects and regulation of the balance between the inflammatory cascade and generation of endogenous spinal cord neurons by using a spinal cord-derived neural stem cell culture system as well as SD rat SCI model. Activation of PPAR-γ could promote neural stem cell proliferation and inhibit PKA expression and neuronal formation in vitro. In the SD rat SCI model, the rosiglitazone + forskolin group showed better locomotor recovery compared to the rosiglitazone and forskolin groups. MAP2 expression was higher in the rosiglitazone + forskolin group than in the rosiglitazone group, NF-κB expression was lower in the rosiglitazone + forskolin group than in the forskolin group, and NeuN expression was higher in the rosiglitazone + forskolin group than in the forskolin group. PPAR-γ activation likely inhibits NF-κB, thereby reducing the inflammatory cascade, and PKA activation likely promotes neuronal cell regeneration.
RESUMO
This paper studied the effects of two amendments (iron sulfate[Fe2 (SO4)3] and calcium carbonate[CaCO3]) on the bioavailability of Pb, Cd and As in a garden soil and on the migration and accumulation of Pb, Cd and As in pepper through an in-situ experiment planting pepper plants. The results indicated that:â Addition of these amendments significantly decreased TCLP extractable contents of Pb and Cd in soil, and increased TCLP extractable contents of As.â¡Compared with the control group, addition of Fe2 (SO4)3 led to reduction in contents of Pb and Cd in pepper fruits by 7.2%-22.9% and 2.3%-2.9%, respectively, but no obvious changes were observed for As contents in pepper fruits. Meanwhile, addition of CaCO3 decreased the contents of Pb, Cd and As in pepper fruits by 15.8%-16.3%, 11.8%-15.0%, and 0.03%-53.2%, respectively. â¢The maximum reductions for the translocation factors of Pb, Cd and As from stem to fruits in pepper plants were 16.7%, 68.0%, 10.2%, respectively, due to Fe2(SO4)3 application and 16.7%, 51.5%, 45.6%, respectively, due to CaCO3 application, compared with the control group. It was obvious that Fe2 (SO4)3 and CaCO3 could both effectively decrease the migration of soil Pb, Cd and As to pepper plants, but the effects of CaCO3 were better than those of Fe2 (SO4)3.
Assuntos
Arsênio/isolamento & purificação , Cádmio/isolamento & purificação , Carbonato de Cálcio/química , Compostos Férricos/química , Chumbo/isolamento & purificação , Poluentes do Solo/isolamento & purificação , Jardins , Solo , VerdurasRESUMO
The disodium hydrogen phosphate (DSP) and hydroxyapatite (HAP) were added into arsenic contaminated soil, then rice pot experiment was conducted to study the effects of phosphorus (P)-containing substances on arsenic (As) uptake by rice. The results showed that: DSP and HAP significantly increased soil pH and the contents of available P in soil (P < 0.05), activating soil arsenic. And DSP was stronger than HAP in improving the migration ability of As in soil. DSP and HAP treatments both significantly reduced the contents of total As in root, as well as total As and inorganic As in brown rice. But HAP significantly increased total As contents in stem. DSP and HAP treatments had better reducing effects on inorganic As than on total As in brown rice. And DSP had the same reducing effects as HAP on total As and inorganic As in brown rice. Analysis results showed that the contents of As in rice were affected by the antagonism between P and As and the increase of As bio-availability in soil. The antagonism played the major role in this study and it was clearly exhibited in both root and rice. Lower dosage (< or = 0.12 g x kg(-1)) of DSP and HAP increased total biomass of rice and brown rice yield, but with the increase of P addition, the two kinds of P-containing substances obviously inhibited the growth of rice, and inhibition by HAP was relatively light.