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1.
Acta Neurochir Suppl ; 127: 35-41, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407060

RESUMO

Given the poor outcome of subarachnoid hemorrhage due to rupture of intracranial aneurysms (IAs) and high prevalence of IAs in general public, elucidation of mechanisms underlying the pathogenesis of the disease and development of effective treatment are mandatory for social health. Recent experimental findings have revealed the crucial contribution of macrophage-mediated chronic inflammation to and greatly promoted our understanding of the pathogenesis. Also a series of studies have proposed the potential of anti-inflammatory drugs as therapeutic ones. In this process, a rodent model of IAs plays an indispensable role. Basic concept of IA induction in such kind of models is that IA formation is triggered by hemodynamic stress loaded on damaged arterial walls. To be more precise, although detailed procedures are different among researchers, animals are subjected to a ligation of a unilateral carotid artery and systemic hypertension achieved by a salt overloading, and IAs are induced at the contralateral bifurcation site. Importantly, trigger of IA formation in the model mimics human one, and IA lesions induced share similarity in histology with human ones such as degenerative changes of media. For further elucidating the pathogenesis, we need to well understand variations, usefulness, and also limits of this model.


Assuntos
Modelos Animais de Doenças , Hemodinâmica , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Animais , Humanos , Inflamação , Macrófagos , Ratos
2.
Acta Neurochir Suppl ; 127: 43-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407061

RESUMO

Early brain injury is now considered as an important cause of delayed neurological deterioration after aneurysmal subarachnoid hemorrhage (SAH), and neuronal apoptosis is one of the constituents of early brain injury. Caspase family is popular proteases in apoptotic pathways, but there also exist caspase-independent cell death pathways in many pathologic states. In this study, we investigated the ratio of caspase-related and caspase-unrelated neuronal deaths in a mice endovascular perforation SAH model. At 24 h after SAH, about half of neurons in the perforation-side cortex showed increased cleaved caspase-3 immunoreactivity. On the other hand, about half of cleaved caspase-3-immunonegative neurons showed abnormal morphology, suggesting that they were in the process of some sort of cell death in the absence of caspase-3 activity. These findings suggest that both caspase-dependent and caspase-independent signaling pathways may cause neuronal death after SAH.


Assuntos
Caspases , Hemorragia Subaracnóidea , Animais , Apoptose , Caspases/metabolismo , Camundongos , Neurônios , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/enzimologia
3.
Acta Neurochir Suppl ; 127: 47-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407062

RESUMO

BACKGROUND: Previously studies have shown that Nox2 and Nox4, as members of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, Nox), participate in brain damage caused by ischemia-reperfusion (I/R). The aim of this study is to investigate the effects of specific chemical inhibitors of Nox2 and Nox4 on cerebral I/R-induced brain injury in rats. METHODS: At 0.5 h before MCAO surgery, the rats were pretreated with vehicle, Nox2 inhibitor (gp91ds-tat), and Nox4 inhibitor (GKT137831), respectively. After reperfusion for 24 h, the infarct sizes of brain tissues in rats in various groups are determined. The penumbra (ischemic) tissues are collected to measure ROS levels, neuronal apoptosis, and degeneration, as well as the integrity of the blood-brain barrier (BBB) in brain tissues of rats. RESULTS: gp91ds-tat and GKT137831 pretreatment significantly reduced the infarct sizes in brain tissues of rats, effectively suppressed I/R-induced increase in ROS levels, neuronal apoptosis and degeneration, and obviously alleviated BBB damage. CONCLUSION: Under cerebral I/R conditions, Nox2 inhibitor (gp91ds-tat) and Nox4 inhibitor (GKT137831) can effectively play a protective role in the brain tissues of rats.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , NADPH Oxidase 2 , NADPH Oxidase 4 , Traumatismo por Reperfusão , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , NADPH Oxidase 2/antagonistas & inibidores , NADPH Oxidase 2/metabolismo , NADPH Oxidase 4/antagonistas & inibidores , NADPH Oxidase 4/metabolismo , NADPH Oxidases , Ratos , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão/metabolismo
4.
Acta Neurochir Suppl ; 127: 59-64, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407064

RESUMO

BACKGROUND: It is reported that the expression of aquaporin4 (AQP4) in the brain is increased and leads to the brain edema after subarachnoid hemorrhage (SAH). In this study, by using AQP4 knockout rat model, the opposite role of AQP4 in early brain injury following SAH through modulation of interstitial fluid (ISF) transportation in the brain glymphatic system had been explored. METHODS: The SAH model was established using endovascular perforation method, the AQP4 knockout rat model was generated using TALENs (transcription activator-like (TAL) effector nucleases) technique. The animals were randomly divided into four groups: sham (n = 16), AQP4-/-sham (n = 16), SAH (n = 24), and AQP4-/-SAH groups (n = 27). The roles of AQP4 in the brain water content and neurological function were detected. In addition, immunohistochemistry and Nissl staining were applied to observe the effects of AQP4 on the blood-brain barrier (BBB) integrity and the loss of neurons in the hippocampus. To explore the potential mechanism of these effects, the distribution of Gd-DTPA (interstitial fluid indicator) injected from cisterna magna was evaluated with MRI. RESULTS: Following SAH, AQP4 knockout could significantly increase the water content in the whole brain and aggravate the neurological deficits. Furthermore, the loss of neuron and BBB disruption in hippocampus were also exacerbated. The MRI results indicated that the ISF transportation in the glymphatic system of AQP4 deficit rat was significantly injured. CONCLUSION: AQP4 facilitates the ISF transportation in the brain to eliminate the toxic factors; AQP4 knockout will aggravate the early brain injury following SAH through impairment of the glymphatic system.


Assuntos
Aquaporina 4 , Edema Encefálico , Lesões Encefálicas , Hemorragia Subaracnóidea , Animais , Aquaporina 4/fisiologia , Encéfalo , Lesões Encefálicas/etiologia , Técnicas de Inativação de Genes , Sistema Glinfático , Ratos , Hemorragia Subaracnóidea/genética , Hemorragia Subaracnóidea/patologia
5.
Acta Neurochir Suppl ; 127: 69-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407066

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe and emergent cerebrovascular disease, the prognosis of which usually very poor. Microthrombi formation highlighted with inflammation occurs early after SAH. As the main cause of DCI, microthrombosis associated with the prognosis of SAH. The aim of this study was to show HSP90 inhibitor 17-AAG effect on microthrombosis after SAH in rats. METHODS: Ninety-five SD rats were used for the experiment. For time course study, the rats were randomly divided into five groups: sham group and SAH group with different time point (1d, 2d, 3d, 5d). Endovascular perforation method was conducted for SAH model. Neurological score, SAH grade, and mortality were measured after SAH. The samples of the left hemisphere brain were collected. The expression of HSP90 was detected by Western blot. The microthrombosis after SAH in rats' brain was detected by immunohistochemistry. For mechanism study, rats were randomly divided into three groups: sham, SAH + vehicle, and SAH +17-AAG (n = 6/group). 17-AAG was given by intraperitoneal injection (80 mg/kg) 1 h after SAH. Neurological function were measured at 24 h after SAH. The expression of RIP3, NLRP3, ASC, and IL-1ß was measured by Western blot. Microthrombosis was detected by immunohistochemistry. RESULTS: Our results showed that the HSP90 protein level increased and peaked at 2 days after SAH. Microthrombosis caused by SAH was increased in 1 day and peaked at 2 days after SAH. Administration HSP90 specific inhibitor 17-AAG reduced expression of RIP3, NLRP3, ASC, and IL-1ß, reduced microthrombosis after SAH, and improved neurobehavior when compared to vehicle group. CONCLUSIONS: 17-AAG can ameliorate microthrombosis via HSP90/RIP3/NLRP3 pathway and improve neurobehavior after SAH.


Assuntos
Inibidores Enzimáticos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Hemorragia Subaracnóidea , Trombose , Animais , Córtex Cerebral , Inibidores Enzimáticos/farmacologia , Proteínas de Choque Térmico HSP90 , Inflamação , Ratos , Ratos Sprague-Dawley , Proteína Serina-Treonina Quinases de Interação com Receptores , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Trombose/tratamento farmacológico
6.
Acta Neurochir Suppl ; 127: 83-89, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407068

RESUMO

There is considerable variability in the presentation of patients with acute subarachnoid hemorrhage (aSAH). Evidence suggests that a thick, diffuse clot better predicts the development of delayed cerebral ischemia and poor outcomes. In a rodent model of acute SAH, we directly measured the effects of the volume of blood injected versus the pattern of distribution of hemorrhage in the subarachnoid space on markers of early brain injury, namely, cerebral blood flow (CBF), cerebrospinal fluid (CSF) concentrations of P450 eicosanoids and catecholamines, and cortical spreading depolarizations (CSDs). There is a significant decrease in CBF, an increase in CSF biomarkers, and a trend toward increasing frequency and severity of CSDs when grouped by severity of hemorrhage but not by volume of blood injected. In severe hemorrhage grade animals, there was a progressive decrease in CBF after successive CSD events. These results suggest that the pattern of SAH (thick diffuse clots) correlates with the "clinical" severity of SAH.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Infarto Cerebral , Circulação Cerebrovascular , Hemorragia Subaracnóidea , Animais , Humanos , Ratos
7.
Acta Neurochir Suppl ; 127: 105-119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407071

RESUMO

The protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway, which is a branch of the unfolded protein response, participates in a range of pathophysiological processes of neurological diseases. However, few studies have investigated the role of the PERK in intracerebral hemorrhage (ICH). The present study evaluated the role of the PERK pathway during the early phase of ICH-induced secondary brain injury (SBI) and its potential mechanisms. An autologous whole blood ICH model was established in rats, and cultured primary cortical neurons were treated with oxyhemoglobin to mimic ICH in vitro. We found that levels of phosphorylated alpha subunit of eukaryotic translation initiation factor 2 (p-eIF2α) and activating transcription factor 4 (ATF4) increased significantly and peaked at 12 h during the early phase of the ICH. To further elucidate the role of the PERK pathway, we assessed the effects of the PERK inhibitor, GSK2606414, and the eIF2α dephosphorylation antagonist, salubrinal, at 12 h after ICH both in vivo and in vitro. Inhibition of PERK with GSK2606414 suppressed the protein levels of p-eIF2α and ATF4, resulting in increase of transcriptional activator CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12, which promoted apoptosis and reduced neuronal survival. Treatment with salubrinal yielded opposite results, which suggested that activation of the PERK pathway could promote neuronal survival and reduce apoptosis. In conclusion, the present study has demonstrated the neuroprotective effects of the PERK pathway during the early phase of ICH-induced SBI. These findings highlight the potential value of PERK pathway as a therapeutic target for ICH.


Assuntos
Lesões Encefálicas , Hemorragia Cerebral , RNA , eIF-2 Quinase , Animais , Lesões Encefálicas/metabolismo , Hemorragia Cerebral/metabolismo , Fator de Iniciação 2 em Eucariotos , Ratos , eIF-2 Quinase/metabolismo
8.
Toxicol Lett ; 318: 44-49, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31639409

RESUMO

Acrolein is a neurotoxin produced through lipid peroxidation in the brain affected by ischemic stroke, which results in neuronal cell injury and inflammation. However the mechanism underlying acrolein-induced brain inflammation remains unclear. Therefore we examined how acrolein leads to astrocytic inflammation. It was found that acrolein increased the levels of NLRP3 and cleaved caspase-1, which led to the maturation of interleukin-1ß (IL-1ß). ELISA assay results, which showed that acrolein increased the secreted IL-1ß, further supported acrolein-induced astrocytic inflammation. Acrolein increased ADAM10 protein levels and the cleavage of N-cadherin. The ADAM10 inhibitor, GI 254023X blocked N-cadherin cleavage by acrolein, suggesting that ADAM10 is an upstream of N-cadherin. Furthermore, we found that acrolein activated p38 MAPK and NF-κB p65, while pretreatment with p38 MAPK inhibitor, SB203580 and GI 254023X inhibited NF-κB p65 activation and NLRP3 inflammasome. This suggests that p38 MAPK mediates the activation of NF-κB p65, which is associated with NLRP3 expression. Finally, we showed that acrolein induced cell toxicity and decrease of EAAT1 expression, suggesting that acrolein may induce a loss of glutamate uptake function. In conclusion, we demonstrate that acrolein induces astrocytic inflammation through NLRP3 inflammasome, which is regulated by ADAM10 and attributed to p38 MAPK-activated NF-κB p65 activity.


Assuntos
Proteína ADAM10/metabolismo , Acroleína/toxicidade , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encefalite/induzido quimicamente , Inflamassomos/efeitos dos fármacos , Proteína ADAM10/genética , Animais , Astrócitos/enzimologia , Astrócitos/patologia , Encéfalo/enzimologia , Encéfalo/patologia , Caderinas/metabolismo , Caspase 1/metabolismo , Linhagem Celular , Encefalite/enzimologia , Encefalite/patologia , Transportador 1 de Aminoácido Excitatório/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Food Chem ; 302: 125328, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404868

RESUMO

To control the oral bioavailability of curcumin, we fabricated solid lipid nanoparticles (SLNs) using tristearin and polyethylene glycol (PEG)ylated emulsifiers. Lipolysis of prepared SLNs via simulated gastrointestinal digestion was modulated by altering the types and concentrations of emulsifiers. After digestion, the size/surface charge of micelles formed from SLN digesta were predictable and >91% of curcumin was bioaccessible in all of the SLNs. The curcumin permeation rate through mucus-covered gut epithelium in vitro was dependent on the size/surface charge of the micelles. Curcumin loaded in long-PEGylated SLNs rapidly permeated the epithelium due to the neutral surface charge of the micelles, resulting in a >12.0-fold increase in bioavailability compared to curcumin solution in a rat model. These results suggest that the bioavailability of curcumin can be controlled by modulating the interfacial properties of SLNs, which will facilitate the development of curcumin formulations for use in functional foods and pharmaceuticals.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Emulsificantes/química , Nanopartículas/química , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Digestão , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Lipídeos/química , Masculino , Nanopartículas/administração & dosagem , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Triglicerídeos/química
10.
Rev. Esc. Enferm. USP ; 53: e03487, Jan.-Dez. 2019. tab, graf
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1020392

RESUMO

RESUMO Objetivo Avaliar o efeito da Justicia acuminatissima , Sara Tudo do Amazonas, na função renal, na hemodinâmica renal, no perfil oxidativo e na histologia renal em ratos com injúria renal aguda isquêmica. Método Ensaio pré-clínico com ratos Wistar, adultos, machos (250-350 g), distribuídos nos grupos Sham, Isquemia e Isquemia + Sara Tudo. Foram avaliados os parâmetros hemodinâmicos, a função renal, o estresse oxidativo e a histologia renal. Resultados O pré-tratamento com o Sara Tudo atenuou a lesão funcional, o que foi evidenciado pelo aumento no clearance de creatinina, redução dos marcadores oxidativos e elevação de tióis, pela melhora significativa do fluxo sanguíneo renal, diminuição da resistência vascular renal e redução da lesão tubulointersticial no tecido renal. Conclusão A renoproteção da Justicia acuminatissima , Sara Tudo, na injúria renal aguda isquêmica, caracterizou-se por melhora significativa da função renal, reduzindo a lesão oxidativa, com impacto positivo na histologia renal.


RESUMEN Objetivo Evaluar el efecto de la planta Justicia acuminatissima , "Sana Todo del Amazonas", en la función renal, la hemodinámica renal, el perfil oxidativo y la histología renal en ratones con injuria renal aguda isquémica. Método Ensayo pre clínico con ratones Wistar, adultos, machos (250-350 g), distribuidos en los grupos Sham, Isquemia e Isquemia + Sana Todo. Fueron evaluados los parámetros hemodinámicos, la función renal, el estrés oxidativo y la histología renal. Resultados El pre tratamiento con el Sana Todo atenuó la lesión funcional, lo que fue evidenciado por el aumento en el aclaramiento de creatinina, reducción de los marcadores oxidativos y elevación de tioles, por la mejora significativa del flujo sanguíneo renal, disminución de la resistencia vascular renal y reducción de la lesión tubulointersticial en el tejido renal. Conclusión La renoprotección de la Justicia acuminatissima , "Sana Todo del Amazonas", en la injuria renal aguda isquémica se caracterizó por mejora significativa de la función renal, reduciendo la lesión oxidativa, con impacto positivo en la histología renal.


ABSTRACT Objective To evaluate the effects of Justicia acuminatissima , or Amazonian Sara Tudo , on renal hemodynamics, oxidative profile, and renal histology in rats with ischemic acute kidney injury. Method Preclinical assay with adult male Wistar rats, weighing from 250 g to 350 g, distributed into Sham, ischemia, and ischemia + Sara Tudo groups. Hemodynamic parameters, renal function, oxidative stress, and renal histology were evaluated. Results Pretreatment with Sara Tudo reduced the functional injury, which was shown by the increase in creatinine clearance and thiols; reduction of oxidative markers, renal vascular resistance, and tubulointerstitial injury in the renal tissue; and the significant improvement in renal blood flow. Conclusion The renoprotection provided by Justicia acuminatissima , or Sara Tudo , in cases of ischemic acute kidney injury was characterized by a marked improvement in renal function, reducing the oxidative injury, and impacting on renal histology positively.


Assuntos
Ratos , Reperfusão , Medicamentos Fitoterápicos , Lesão Renal Aguda , Terapias Complementares , Ratos Wistar , Experimentação Animal
11.
Oral Maxillofac Surg ; 23(4): 473-479, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31686251

RESUMO

OBJECTIVES: To evaluate the mandible and tibia of rats treated with bisphosphonates (BPs) by imaging and histomorphometric analysis. STUDY DESIGN: Thirty-four rat specimens (Rattus norvegicus, Wistar strain) were distributed into 3 groups: (1) 12 rats treated with zoledronic acid; (2) 12 rats treated with clodronate; and (3) the control group, containing 10 rats that received saline. All bones were exposed to cone beam computed tomography (CBCT). The images were analyzed to determine bone density (BD), using the software OsiriX 7.0. Histological slides were prepared from the specimens and the proportion of bone volume (BV) was quantified using the software Adobe Photoshop CC. RESULTS: There was no statistically significant difference in BD either between the drug groups or between mandible and tibia. BV between BPs and control group did not show a significant difference. However, comparing the two bones, the mandibles in the control group displayed higher BV than did the tibiae in the same group. CONCLUSION: According to our results, we conclude that (1) BD was not altered by bone type or by type of BP administered, and (2) treatment with zoledronic acid or clodronate did not affect BV in the mandible or tibia of test groups.


Assuntos
Conservadores da Densidade Óssea , Difosfonatos , Animais , Mandíbula , Ratos , Ratos Wistar , Tíbia
12.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 722-727, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726500

RESUMO

Objective: To investigate the mechanism of Al (mal) (3)-induced ferroptosis in rat adrenal pheochromocytoma cells (PC12), to explore the effect of deferoxamine (DFO) . Methods: Taken PC12 cells growing at logarithmic phase and divided into 6 groups: control group, 200 µmol/L Al (mal) (3) group, 0.5% DMSO group, 200 µmol/L DFO group, Al (mal) (3)+DMSO group, Al (mal) (3)+DFO group. DMSO and DFO were added to the DMSO group and the Al (mal) (3)+DMSO group, the DFO group and the Al (mal) (3)+DFO group for 2 h, respectively, Al (mal) (3) was then added to the Al (mal) (3) group, Al (mal) (3)+DMSO group, and the Al (mal) (3)+DFO group to a final concentration of 200 µmol/L. The cell viability was detected by CCK8, the morphology and ROS levels of PC12 cells was observed by inverted microscope, the cell proliferation toxicity and intracellular iron ion content were detected by colorimetry, the GSH content and GSH-PX activity were detected by biochemical method. Results: Al (mal) (3) exposure significantly inhibited the growth of PC12 cells and destroyed the cell morphological structure, resulting in increased LDH activity and intracellular iron ion content in PC12 cells, decreased GSH content and GSH-PX activity, increased ROS levels; the combined treatment of Al (mal) (3)+DFO can significantly improve the cell viability of PC12 cells, improved cell morphology, decreased cell LDH activity and intracellular iron ion content (P>0.05), increased GSH content and GSH-PX activity, decreased ROS levels. Conclusion: Al (mal) (3) can induce ferroptosis in PC12 cells, DFO may inhibit ferroptosis by reducing intracellular iron levels and reducing oxidative damage.


Assuntos
Apoptose/efeitos dos fármacos , Desferroxamina/farmacologia , Ferro/análise , Alumínio , Animais , Sobrevivência Celular , Estresse Oxidativo , Células PC12 , Ratos
13.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 728-731, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726501

RESUMO

Objective: To observe the lung injury of male rats induced by sub-chronic exposure to crotonaldehyde, and to explore the possible mechanism of injury. Methods: Forty SPF male Wistar rats were randomly divided into control group and 3 groups in each group, and each group received 0.0, 2.5, 4.5, 8.5 mg/kg body weight crotonaldehyde solution for continuous intragastric administration. 120 d, once a day. After the end of the exposure, the body weight of the rats was measured, and the lung tissues were quickly separated after cervical dislocation. The organ coefficients were calculated and histopathological examination was performed to determine malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione. Peroxidase (GSH-Px) content; ELISA was used to measure interleukin (IL) -6, IL-1ß, and tumor necrosis factor (TNF) -α in lung tissues. Results: Compared with the control group, the weight gain of the rats in the 4.5 and 8.5 mg/kg exposure groups was small, and the lung weight and organ coefficient of the exposed group decreased, the difference was statistically significant (P<0.05). In the exposed group, the lung tissue structure was disordered, the alveolar wall was thickened, and inflammatory cell infiltration was observed. Compared with the control group, the MDA activity in the serum of the rats in the 4.5 mg/kg and 8.5 mg/kg groups increased, and the SOD and GSH-Px activities decreased, the difference was statistically significant (P<0.05). TNF-α levels in the lung tissues of rats exposed to 4.5 mg/kg and 8.5 mg/kg, and levels of (IL) -6 and IL-1ß in the lungs of rats in the 2.5, 4.5, and 8.5 mg/kg groups. Significantly increased, the difference was statistically significant (P<0.05) . Conclusion: Crotonaldehyde may induce inflammatory and oxidative stress damage in rats by up-regulating the expression of inflammatory factors in lung tissue and changing the oxidative balance.


Assuntos
Inflamação , Lesão Pulmonar/induzido quimicamente , Estresse Oxidativo , Aldeídos , Animais , Glutationa/análise , Pulmão , Masculino , Malondialdeído/análise , Peroxidase/análise , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/análise , Fator de Necrose Tumoral alfa/análise
14.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 737-745, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726503

RESUMO

Objective: To investigate the antioxidant mechanism of diallyl sulfide (DAS) in antagonizing the reduction in peripheral blood white blood cells (WBC) induced by benzene in rats. Methods: A total of 60 specific pathogen-free adult male Sprague-Dawley rats, with a body weight of 180-220 g, were selected, and after 5 days of adaptive feeding, they were randomly divided into blank control group, DAS control group, benzene model group, benzene+low-dose DAS group, benzene+middle-dose DAS group, and benzene+high-dose DAS group, with 10 rats in each group. The rats in the benzene+low-dose DAS group, the benzene+middle-dose DAS group, the benzene+high-dose DAS group, and the DAS control group were given DAS by gavage at a dose of 40, 80, 160, and 160 mg/kg·bw, respectively, and those in the blank control group and the benzene model group were given an equal volume of corn oil; 2 hours later, the rats in the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group were given a mixture of benzene (1.3 g/kg·bw) and corn oil (with a volume fraction of 50%), and those in the blank control group and the DAS control group were given an equal volume of corn oil. The above treatment was given once a day for 4 consecutive weeks. At 1 day before treatment, anticoagulated blood was collected from the jugular vein for peripheral blood cell counting. After anesthesia with intraperitoneally injected pentobarbital (50 mg/kg·bw), blood samples were collected from the abdominal aorta, serum was isolated, and the thymus, the spleen, and the femur were freed at a low temperature to measure oxidative and antioxidant indices. The femur at one side was freed for WBC counting in bone marrow. Results: Compared with the blank control group, the benzene model group had significant reductions in the volume, weight, and organ coefficient of the spleen and the thymus (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had significant increases in the volume of the spleen and the thymus and the weight and organ coefficient of the spleen (P<0.05), and the benzene+middle-dose DAS group and the benzene+high-dose DAS group had significant increases in the weight and organ coefficient of the thymus (P<0.05). Compared with the blank control group, the benzene model group had a significant reduction in WBC count in peripheral blood and bone marrow (P<0.05), and compared with the benzene model group, the benzene+middle-dose DAS group and the benzene+high-dose DAS group had a significant increase in WBC count in peripheral blood and bone marrow (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the serum level of malondialdehyde (MDA) (P<0.05) and significant reductions in total superoxide dismutase (T-SOD) activity, reduced glutathione (GSH) level, GSH/oxidized glutathione (GSSG) ratio, total antioxidant capacity (T-AOC) (P<0.05) ; compared with the benzene model group, the benzene+high-dose DAS group had a significant reduction in the serum level of MDA and significant increases in T-SOD activity, GSH level, GSH/GSSG ratio, and T-AOC (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA (P<0.05) and significant reductions in GSH level, GSH/GSSG ratio, and T-AOC (P<0.05) in the spleen; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in MDA level (P<0.05) and significant increases in GSH level and T-AOC (P<0.05), and the benzene+high-dose DAS group had significant increases in T-SOD activity and GSH/GSSG ratio (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA in bone marrow cells (BMCs) and peripheral blood mononucleated cells (PBMCs) (P<0.05) and a significant reduction in T-AOC in PBMCs (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in the level of MDA in BMCs and PBMCs (P<0.05), and the benzene+high-dose DAS group had significant increases in GSH level and GSH/GSSG ratio (P<0.05) . Conclusion: DAS can antagonize the benzene-induced reduction in peripheral blood WBC, possibly by exerting an anti-oxidative stress effect.


Assuntos
Compostos Alílicos/farmacologia , Antioxidantes/farmacologia , Leucopenia/tratamento farmacológico , Sulfetos/farmacologia , Animais , Benzeno/efeitos adversos , Glutationa/análise , Leucopenia/induzido quimicamente , Masculino , Malondialdeído/análise , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/análise
15.
Adv Exp Med Biol ; 1101: 123-147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31729674

RESUMO

Brain-machine interface (BMI) provides a bidirectional pathway between the brain and external facilities. The machine-to-brain pathway makes it possible to send artificial information back into the biological brain, interfering neural activities and generating sensations. The idea of the BMI-assisted bio-robotic animal system is accomplished by stimulations on specific sites of the nervous system. With the technology of BMI, animals' locomotion behavior can be precisely controlled as robots, which made the animal turning into bio-robot. In this chapter, we reviewed our lab works focused on rat-robot navigation. The principles of rat-robot system have been briefly described first, including the target brain sites chosen for locomotion control and the design of remote control system. Some methodological advances made by optogenetic technologies for better modulation control have then been introduced. Besides, we also introduced our implementation of "mind-controlled" rat navigation system. Moreover, we have presented our efforts made on combining biological intelligence with artificial intelligence, with developments of automatic control and training system assisted with images or voices inputs. We concluded this chapter by discussing further developments to acquire environmental information as well as promising applications with write-in BMIs.


Assuntos
Controle Comportamental , Interfaces Cérebro-Computador , Robótica , Animais , Encéfalo/fisiologia , Locomoção , Ratos
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 794-799, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750820

RESUMO

Objective To explore the inhibitory effects of polyphenols from Toona sinensis seeds (PTSS) on neuroinflammation and the underlying mechanism in rats with Parkinson's disease (PD). Methods PD rat models were prepared by stereotaxic injection of 6-hydroxydopamine (6-OHDA) into one side of striatum of Sprague-Dawley male rats. Model rats were randomly divided into model group and PTSS group (n=10), and a normal control group was set as well (n=10). The rotational behavior of rats was induced by intraperitoneal injection of apomorphine (APO) after 30 days, and the behavioral changes of rats from each group were investigated. The morphological and quantity changes of DA neurons (tyrosine hydroxylase positive, TH-positive), microglia cells (ionized calcium binding adaptor molecule-1, Iba1-positive) and astrocytes (glial fibrillary acidic protein, GFAP-positive) in substantia nigra (SN) of rats from each group were examined by immunohistochemistry. Inducible nitric oxide synthase (iNOS), nuclear factor-κB p65 (NF-κBp65), p38 mitogen-activated protein kinase (p38MAPK) and phosphor-p38 mitogen-activated protein kinase (p-p38MAPK) levels were evaluated through immunohistochemical staining. The protein levels of TH, GFAP, p38MAPK and p-p38MAPK in SN were examined by Western blot analysis. Results The number of rotations in the rats of the PTSS group was significantly reduced compared with that in the model group. The number of TH-positive cells in the model group was much less than that in the control group. The number and protein levels of TH-positive cells were enhanced significantly by PTSS intervention. Compared with the control group, the protein levels of Iba1, GFAP, iNOS, NF-κB, p38MAPK and p-p38MAPK in the injured side of the model group significantly increased, which could be suppressed significantly by PTSS intervention. Conclusion PTSS demonstrates protective effects on DA neurons by inhibiting p38MAPK signaling pathway and reducing the expression of inflammatory factors in PD rats.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Meliaceae/química , Doença de Parkinson/tratamento farmacológico , Polifenóis/farmacologia , Sementes/química , Animais , Masculino , Oxidopamina , Compostos Fitoquímicos/farmacologia , Ratos , Ratos Sprague-Dawley , Substância Negra
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 812-816, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750823

RESUMO

Objective To investigate the effect of aldosterone (ALD) on the migration of rat hepatic stellate cells (HSC-T6) and its mechanism. Methods HSC-T6 cells were cultured and divided into control group (treated with medium only), ALD group (only 1 nmol/L ALD, 24 hours), spironolactone pre-treated group (a specific inhibitor of ALD receptor 10 nmol/L spironolactone at 1 hours before ALD treatment), Y27632 pre-treated group (a RhoA kinase inhibitor 10 nmol/L Y27632 at 1 hours before ALD treatment). A TranswellTM chamber system was used to observe the change of migration in the different groups. Changes in actin cytoskeletal organization were visualized by fluorescence staining using rhadamin-labeled phalloidin and fluorescence images were recorded using confocal microscopy. The levels of phosphorylated myosinlight chain (p-MLC) and phosphorylated moesin (p-moesin) in the RhoA/ROCK signaling pathway were evaluated by Western blotting in HSC-T6 cells. Results ALD treatment of HSC-T6 resulted in the enhancement of migration, but the effect of ALD-induced migration could be inhibited by spironolactone and Y27632. Stimulation of HSC-T6 with ALD induced a rapid morphological change conconmitant with a robust reorganization of actin cytoskeleton, while the morphological change was suppressed by spironolactone and Y27632. The effect of aldosterone on the activation of HSC migration was mediated by p-MLC and p-moesin protein expressions through the RhoA/ROCK signaling pathway. Spironolactone and Y27632 had the ability to block aldosterone-induced protein expressions in HSC-T6 cells. Conclusion ALD can induce the migration of activated HSC-T6 cells through the activation of the RhoA/ROCK signaling pathway.


Assuntos
Aldosterona/farmacologia , Movimento Celular , Células Estreladas do Fígado/efeitos dos fármacos , Transdução de Sinais , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Amidas , Animais , Células Cultivadas , Células Estreladas do Fígado/citologia , Piridinas , Ratos , Espironolactona
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 823-827, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750825

RESUMO

Objective To study the characteristics of the expression of aquaporin-4 (AQP4) in the brains and astrocytes of rats with thermoplegia. Methods Sixty healthy male Sprague-Dawley rats weighing (250±30) g were randomly divided into control group and model group. The quiet exposure method with high temperature (40DegreesCelsius) and high humidity (70%) was used to make a typical rat model of thermoplegia to monitor rectal temperature and record onset time every 10 minutes. When the temperature of stressed rats reached 42.5 DegreesCelsius, it was regarded as onset time of the disease. The rats in both groups were placed at 26DegreesCelsius with humidity 60% later. After 5-hour observation and their behavior evaluation, the rats were killed and their brain tissues were taken for measuring the water content of the tissues. The astrocytes of the rats were cultured at 37DegreesCelsius and 41DegreesCelsius. AQP4 mRNA and protein expression were detected by reverse-transcription PCR and Western blot analysis. Results Compared with the control group, the expression of AQP4 mRNA and protein were significantly lower in the model group than in the control group. Conclusion High temperature may lead to the destruction of blood-brain barrier and the down-regulation of AQP4 mRNA and protein expression in experimental rats, which can induce the occurrence and development of cerebral edema in experimental rats.


Assuntos
Aquaporina 4/metabolismo , Barreira Hematoencefálica , Edema Encefálico/patologia , Golpe de Calor/patologia , Animais , Astrócitos , Encéfalo/metabolismo , Temperatura Alta , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
19.
Zhonghua Yi Xue Za Zhi ; 99(43): 3428-3431, 2019 Nov 19.
Artigo em Chinês | MEDLINE | ID: mdl-31752473

RESUMO

Objective: To evaluate the value of Gd-BOPTA enhanced MRI in the staging of liver fibrosis. Method: Fifty male SD rats (6-week-old, 180-220 g) were divided into the modeling group (n=42) and the control group (n=8). The model of liver fibrosis in the modeling group was established by carbon tetrachloride (animal license No. SYXK (Su) 2017-0043). From week 2 to week 10, rats in the modeling group (n=4) and control group (n=1) were randomly selected to scan 1 h(RER1), 2 h(RER2) and 3 h(RER3) after injection of Gd-BOPTA, respectively, to measure the relative enhancement rate (RER) of liver parenchyma. The shape of intrahepatic bile duct and the degree of enhancement at each time point were observed. Results: Forty-two rats (34 rats in the modeling group and 8 rats in the control group) completed the experiment. RER1, RER2 and RER3 of the control group were 1.44±0.37, 1.22±0.37 and 0.84±0.28 respectively. RER1, RER2 and RER3 of the modeling group were respectively: S1 (n=6): 1.49±0.48, 1.29±0.39, 0.91±0.38;S2 (n=9): 1.48±0.44, 1.34±0.37, 1.04±0.40;S3 (n=11): 1.49±0.43, 1.37±0.39, 1.21±0.30; S4 (n=8): 1.49±0.44, 1.40±0.37, 1.24±0.40. There was no significant difference in RER1 and RER2 values between the control group and the liver fibrosis group (F=0.022, P=0.999; F=0.301, P=0.875). There were significant differences between the control group and RER3 values of hepatic fibrosis stage S3 and S4 (t=2.249, P=0.031; t=2.274, P=0.029), there was no significant difference between the remaining groups (all P>0.05).In the control group, the intrahepatic bile duct was obviously strengthened within 1 hour after enhancement, and walked naturally. The intrahepatic bile duct was slightly enhanced 1h after the enhancement of S3-S4 stage of hepatic fibrosis, and the intrahepatic bile duct was significantly enhanced 2-3 hours later, with distorted alignment. Conclusion: Delayed 3 hours liver parenchymal RER and intrahepatic bile duct distortion delay enhancement after Gd-BOPTA enhancement contribute to the S3-S4 diagnosis of liver fibrosis.


Assuntos
Cirrose Hepática , Animais , Meios de Contraste , Gadolínio DTPA , Imagem por Ressonância Magnética , Masculino , Meglumina/análogos & derivados , Compostos Organometálicos , Ratos , Ratos Sprague-Dawley
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1110-1115, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753094

RESUMO

OBJECTIVE: To study the effect of PR-957 on the formation of A1 reactive astrocytes. METHODS: The cerebral cortices of 1-day-old female rats were obtained and cultured for primary astrocytes. These cells were divided into 3 groups: control, lipopolysaccharide (LPS), and LPS+PR-957. The LPS group was treated with LPS (at a concentration of 5 µmol/L) for 48 hours; the LPS+PR-957 group was treated with PR-957 (at a final concentration of 200 nmol/L) for 1 hour and then LPS for 48 hours. Enzyme-linked immunosorbent assay was used to determine the expression of complement 3 (C3, a marker for A1 reactive astrocytes) and tumor necrosis factor alpha (TNF-α). Quantitative real-time PCR was used to determine the relative mRNA expression of glypican-6 (GPC6), SPARC-like 1 (SPARCL1), and lipocalin-2 (LCN2). All the above experiments were repeated three times independently. RESULTS: C3 expression was almost not observed in the control group, but was observed in both the LPS group and the LPS+PR-957 group, with significantly lower expression observed in the LPS+PR-957 group (P<0.05). The expression of TNF-α was consistent with that of C3. Compared with the control group, the LPS and the PS+PR-957 groups had significantly reduced mRNA expression levels of GPC6 and SPARCL1 but significantly increased mRNA expression level of LCN2 (P<0.001). Compared with the LPS group, the LPS+PR-957 group had significantly increased mRNA expression levels of GPC6 and SPARCL1 but significantly reduced mRNA expression level of LCN2 (P<0.001). CONCLUSIONS: LPS can induce the transformation from astrocytes to A1 reactive astrocytes, and PR-957 can inhibit the formation of LPS-induced A1 reactive astrocytes.


Assuntos
Astrócitos , Animais , Feminino , Lipopolissacarídeos , Oligopeptídeos , Ratos , Fator de Necrose Tumoral alfa
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