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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(2): 176-180, 2020 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32386044

RESUMO

GABAergic interneurons are neurons that mainly release the neurotransmitter of γ-aminobutyric acid (GABA), accounting for approximately 20% of the total number of neurons in the cerebral cortex. They form wide synaptic connections with the pyramidal cells and regulate the pyramidal activity, playing an important role in maintenance of excitation/inhibition balance in cortical circuits. Recently, studies have shown that GABAergic interneurons dysfunction is the key mechanism underlying neuropsychiatric disorders such as schizophrenia, depression, and autism. N-methyl-D-aspartic acid (NMDA) receptors are the main receptors in GABAergic interneurons, and its dysfunction and different subunit deletions can mediate GABAergic interneuron dysfunction.

2.
Cell Rep ; 31(5): 107596, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32375046

RESUMO

Hypotonic stress causes the activation of swelling-activated nonselective cation channels (NSCCs), which leads to Ca2+-dependent regulatory volume decrease (RVD) and adaptive maintenance of the cell volume; however, the molecular identities of the osmosensitive NSCCs remain unclear. Here, we identified TMEM63B as an osmosensitive NSCC activated by hypotonic stress. TMEM63B is enriched in the inner ear sensory hair cells. Genetic deletion of TMEM63B results in necroptosis of outer hair cells (OHCs) and progressive hearing loss. Mechanistically, the TMEM63B channel mediates hypo-osmolarity-induced Ca2+ influx, which activates Ca2+-dependent K+ channels required for the maintenance of OHC morphology. These findings demonstrate that TMEM63B is an osmosensor of the mammalian inner ear and the long-sought cation channel mediating Ca2+-dependent RVD.

3.
J Mol Neurosci ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32406041

RESUMO

This study investigates the effect of polydatin on the neurological function of cerebral hemorrhage rats and on the Nrf2 pathway of the endogenous antioxidant system in tissues around cerebral hematoma. Further, the study also aims to provide solid insights for clinical diagnosis and treatment. A total of 54 SPF grade male Wistar rats were divided into three groups: the sham group, model group, and polydatin group. Various parameters such as neurological deficit score, brain water content, pathological morphology, oxidative stress index content, Nrf2, NQO1, HO-1 mRNA expression, and the expression of HO-1, Nrf2, and kelch-like epichlorohydrin-1 (Keap1) protein were observed. Compared with the sham group, the mNSS score and brain water content of rats in the model group increased significantly after dosing (P < 0.05). When compared with the model group, the mNSS score and brain water content of rats in the polydatin group decreased significantly after dosing (P < 0.05). Compared with the other group, the serum NSE content of rats in the polydatin group decreased (P < 0.05). An increase was observed in the contents of NO, SOD, MDA, GSSG, and GSH in the brain tissue of rats in the model group when compared with the sham group. Compared with the model group, the contents of NO and MDA in the brain tissue of rats in the polydatin group decreased, while the contents of SOD, GSSG, and GSH increased (P < 0.05). The relative expressions of Nrf2, NQO1, and HO-1mRNA in the brain tissue of rats in the polydatin group was relatively high compared with both groups (P < 0.05). Polydatin can improve the neurological function of ICH rats and reduce the oxidative stress response by regulating the Nrf2-ARE pathway and downstream gene expression. This study preliminarily discussed the relevant mechanism of polydatin in the treatment of ICH rats, thus providing a theoretical reference to ICH treatment.

4.
Small ; : e2000733, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410334

RESUMO

Organolead trihalide perovskites have attracted significant attention for optoelectronic applications due to their excellent physical properties in the past decade. Generally, both grain boundaries in perovskite films and the device structure play key roles in determining the device performance, especially for horizontal-structured device. Here, the first optimized vertical-structured photodetector with the perovskite single crystal MAPbBr3 as the light absorber and graphene as the transport layer is shown. The hybrid device combines strong photoabsorption characteristics of perovskite and high carrier mobility of flexible graphene, exhibits excellent photoresponse performance with high photoresponsivity (≈1017.1 A W-1 ) and high photodetectivity (≈2.02 × 1013 Jones) in a low light intensity (0.66 mW cm-2 ) under the actuations of 3 V bias and laser irradiation at 532 nm. In particular, an ultrahigh photoconductive gain of ≈2.37 × 103 is attained because of fast charge transfer in the graphene and large recombination lifetime in the perovskite single crystal. The vertical architecture combining perovskite crystal with highly conductive graphene offers opportunities to fulfill the synergistic effect of perovskite and 2D materials, is thus promising for developing high-performance electronic and optoelectronic devices.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32419457

RESUMO

Recently, enhancing the performance of flexible perovskite photodetectors through facile and effective means has gained greater attention. In contrast to typical approaches through modifying light-active materials, we present here a simple but effective design by improving light-matter interactions through near-field optical interference on a back-reflected substrate, whose architecture includes a morphologically flat top surface and a back scattering surface textured with micro/nanostructures by the femtosecond laser direct writing. A CH3NH3PbI3 perovskite film and polyethylene terephthalate are selected as the light-active and base materials, respectively. Under a 1 V bias voltage actuation and 532 nm laser irradiation at an intensity of 10 mWcm-2, the flexible device exhibits an excellent performance in photoresponsivity (47.1 mAW-1), detectivity (3.7×1011 Jones) and on/off ratio (4600). Due to the near-field optical enhancement of the substrate and the strong light-matter interaction, the performance parameters above are enhanced by at least five times over a wide spectral range of 220-780 nm. Such enhancement behaviors are independent of active material properties and therefore can be compatible with other operations such as crystalline transformation, doping, and interface modification. Moreover, the alteration of stress distribution on the structured substrate facilitates the bending robustness and stability. These features highlight the potential of back-reflected design in the development of flexible perovskite photoelectric devices, which are especially suitable for large-scale industrial production.

6.
BMC Anesthesiol ; 20(1): 86, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32305062

RESUMO

BACKGROUND: Postoperative pain is the most prominent concern among surgical patients. It has previously been reported that venous cannulation-induced pain (VCP) can be used to predict postoperative pain after laparoscopic cholecystectomy within 90 mins in the recovery room. Its potential in predicting postoperative pain in patients with patient-controlled intravenous analgesia (PCIA) is worth establishing. The purpose of this prospective observational study was to investigate the application of VCP in predicting postoperative pain in patients with PCIA during the first 24 h after laparoscopic nephrectomy. METHODS: One hundred twenty patients scheduled for laparoscopic nephrectomy were included in this study. A superficial vein on the back of the hand was cannulated with a standard-size peripheral venous catheter (1.1 × 3.2 mm) by a nurse in the preoperative areas. Then the nurse recorded the VAS score associated with this procedure estimated by patients, and dichotomized the patients into low response group (VAS scores < 2.0) or high response group (VAS scores ≥2.0). After general anesthesia and surgery, all the patients received the patient-controlled intravenous analgesia (PCIA) with sufentanil. The VAS scores at rest and on coughing at 2 h, 4 h, 8 h, 12 h, 24 h, the effective number of presses and the number of needed rescue analgesia within 24 h after surgery were recorded. RESULTS: Peripheral venous cannulation-induced pain score was significantly correlated with postoperative pain intensity at rest (rs = 0.64) and during coughing (rs = 0.65), effective times of pressing (rs = 0.59), additional consumption of sufentanil (rs = 0.58). Patients with venous cannulation-induced pain intensity ≥2.0 VAS units reported higher levels of postoperative pain intensity at rest (P < 0.0005) and during coughing (P < 0.0005), needed more effective times of pressing (P < 0.0005) and additional consumption of sufentanil (P < 0.0005), and also needed more rescue analgesia (P = 0.01) during the first 24 h. The odds of risk for moderate or severe postoperative pain (OR 3.5, 95% CI 1.3-9.3) was significantly higher in patients with venous cannulation-induced pain intensity ≥2.0 VAS units compared to those <2.0 VAS units. CONCLUSIONS: Preoperative assessment of pain induced by venous cannulation can be used to predict postoperative pain intensity in patients with PCIA during the first 24 h after laparoscopic nephrectomy. TRIAL REGISTRATION: We registered this study in a Chinese Clinical Trial Registry (ChiCTR) center on July 6 2019 and received the registration number: ChiCTR1900024352.

7.
J Neuroinflammation ; 17(1): 110, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32276637

RESUMO

BACKGROUND: Increasing evidence suggests that multiple or long-time exposure to general anaesthesia (GA) could be detrimental to cognitive development in young subjects and might also contribute to accelerated neurodegeneration in the elderly. Iron is essential for normal neuronal function, and excess iron in the brain is implicated in several neurodegenerative diseases. However, the role of iron in GA-induced neurotoxicity and cognitive deficits remains elusive. METHODS: We used the primary hippocampal neurons and rodents including young rats and aged mice to examine whether GA impacted iron metabolism and whether the impact contributed to neuronal outcomes. In addition, a pharmacological suppression of iron metabolism was performed to explore the molecular mechanism underlying GA-mediated iron overload in the brain. RESULTS: Our results demonstrated that GA, induced by intravenous ketamine or inhalational sevoflurane, disturbed iron homeostasis and caused iron overload in both in vitro hippocampal neuron culture and in vivo hippocampus. Interestingly, ketamine- or sevoflurane-induced cognitive deficits, very likely, resulted from a novel iron-dependent regulated cell death, ferroptosis. Notably, iron chelator deferiprone attenuated the GA-induced mitochondrial dysfunction, ferroptosis, and further cognitive deficits. Moreover, we found that GA-induced iron overload was activated by NMDAR-RASD1 signalling via DMT1 action in the brain. CONCLUSION: We conclude that disturbed iron metabolism may be involved in the pathogenesis of GA-induced neurotoxicity and cognitive deficits. Our study provides new vision for consideration in GA-associated neurological disorders.

8.
PLoS One ; 15(4): e0231687, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348339

RESUMO

BACKGROUND: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19. METHODS: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19. RESULTS: Of these 46 cases, 16 cases with confirmed COVID-19 were tested for HFABP> 7 ng / mL upon admission; among them, 14 cases were diagnosed with severe COVID-19 within the hospitalization. The Odds ratio of the measured HFABP elevation was 6.81(95% confidence interval [CI] 5.23-8.40), and 3 patients with severe COVID-19 progressed in 5 patients with mild HFABP> 7 ng/mL. CONCLUSION: These data indicate that the elevation of HFABP is closely related to the severity of COVID-19 in the patients, and the elevated HFABP may cause rapid development of patients with mild COVID-19 into severe COVID-19. But serum HFABP negative maybe make patients with mild COVID-19 safer, the current data show no effect on the all-cause mortality. TRIAL REGISTRATION: Our study has been registered with the Chinese Clinical Trial Registry, the registration number: ChiCTR2000029829.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Proteína 3 Ligante de Ácido Graxo/sangue , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Idoso , Distribuição de Qui-Quadrado , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia Viral/epidemiologia , Prevalência , Prognóstico , Estudos Retrospectivos
11.
J Alzheimers Dis ; 74(3): 875-881, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32144993

RESUMO

Persistent neuropathic pain (NP) causes future development of neurodegenerative diseases, e.g., Alzheimer' disease, and thus needs to be optimally treated. Surgically-induced neuropathic pain (SNPP) is a persistent pain that occurs in nearly half of the individuals after common operations. Here, we showed that specific activation of 5-hydroxytryptamine (5-HT) type 2A receptors by systemic administration of TCB-2 [(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide] improved the function of potassium chloride cotransporter 2 (KCC2), resulting in reduction in neuropathic pain after chronic constriction injury (CCI), a rat model that mimics SNPP. Moreover, TCB-2 administration attenuated both mechanical and thermal hyperalgesia, likely through augmentation of dorsal horn KCC2 levels, since this effect was abolished by intrathecal provision of dihydroindenyl oxy alkanoic acid (DIOA), which blocked the effects of KCC2. Furthermore, TCB-2-mediated re-activation of KCC2 likely reduces future development of neurodegeneration in rats. Together, our data support further studies on the possibility of using this strategy to reduce postoperative pain and future neurodegenerative disorders in clinic.

12.
Cancer Med ; 9(10): 3455-3462, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32207885

RESUMO

BACKGROUND: Whether prognosis differs between lung acinar predominant adenocarcinoma (ACN) and papillary predominant adenocarcinoma (PAP) patients remains controversial. Furthermore, the appropriate surgical plan for each subtype is undetermined. METHODS: Data of stage I ACN or PAP patients from 2004 to 2015 were retrospectively reviewed by SEER*Stat 8.3.5. The primary outcome was overall survival (OS) and lung cancer specific survival (LCSS). RESULTS: 1531 patients (PAP, 484; ACN, 1047) were included. ACN patients had better OS (P = .001) and LCSS (P = .003) than PAP patients. Among stage I ACN patients, lobectomy with mediastinal lymph node dissection (Lob) (P = .001) or segmentectomy (Seg) (P = .003) provided a better OS than wedge resection (Wed). And ACN patients who received Lob had a equivalent LCSS, compared to those who received Seg (P = .895). For patients with PAP in stage I, those who received Lob tended to have a better prognosis than that received Seg (HR of OS, 0.605, 95% CI: 0.263-1.393; HR of LCSS, 0.541, 95% CI: 0.194-1.504) or Wed (HR of OS, 0.735, 95% CI: 0.481-1.123; HR of LCSS, 0.688, 95% CI: 0.402-1.180). CONCLUSIONS: Among patients with lung adenocarcinoma in stage I, those with ACN have a better OS and LCSS than that with PAP. For patients with stage I ACN, Seg and Lob, rather than Wed, seem to be an equivalent treatment choice; however, Seg is the prior option because it could preserve more lung function than Lob. For patients with PAP, Lob tends to be a better choice than Wed and Seg, although the prognostic difference between them is nonsignificant.

13.
Neuroreport ; 31(7): 507-514, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32168099

RESUMO

Postoperative cognitive dysfunction is a well-recognized complication after major surgery in the elderly, but its pathophysiological mechanism is not fully understood. In the present study, we used liquid chromatography-tandem mass spectrometry combined with tandem mass tags to identify differentially expressed proteins and perform further functional studies on protein of interest. Here, we showed that hippocampal complement C3 was significantly upregulated after surgery, which was accompanied by marked decreases in synaptic related proteins and density. In aged patients undergoing gastrointestinal surgery, we also found significantly increased plasma level of C3b postoperatively and were negatively associated with cognitive performance. Notably, selective inhibition of complement C3 by compstatin was able to rescue synaptic and cognitive impairments induced by surgery in aged mice. Collectively, our study confirms that surgery can induce cognitive impairments, and the possible mechanisms might be related to abnormal complement signaling and synaptic disruption.

14.
Brain Behav Immun ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169498

RESUMO

Since December 2019, more than 79,000 people have been diagnosed with infection of the Corona Virus Disease 2019 (COVID-19). A large number of medical staff was sent to Wuhan city and Hubei province to aid COVID-19 control. Psychological stress, especially vicarious traumatization caused by the COVID-19 pandemic, should not be ignored. To address this concern, the study employed a total of 214 general public and 526 nurses (i.e., 234 front-line nurses and 292 non-front-line nurses) to evaluate vicarious traumatization scores via a mobile app-based questionnaire. Front-line nurses are engaged in the process of providing care for patients with COVID-19. The results showed that the vicarious traumatization scores for front-line nurses including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (P < 0.001). Interestingly, the vicarious traumatization scores of the general public were significantly higher than those of the front-line nurses (P < 0.001); however, no statistical difference was observed compared to the scores of non-front-line nurses (P > 0.05). Therefore, increased attention should be paid to the psychological problems of the medical staff, especially non-front-line nurses, and general public under the situation of the spread and control of COVID-19. Early strategies that aim to prevent and treat vicarious traumatization in medical staff and general public are extremely necessary.

15.
Environ Sci Technol ; 54(8): 4820-4828, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32195581

RESUMO

The interaction mechanisms of heavy metals with organo-Fe hydroxides co-precipitates (OFC) remain unclear due to the structural complexity of the OFC. In this study, batch experiments were conducted to investigate the immobilization mechanisms of Cr(III) by the OFC, which was prepared by co-precipitating Fe3+ with rice/rape straw-derived dissolved organic carbon, through sorption and co-precipitation using synchrotron-based X-ray absorption near-edge structure (XANES) spectroscopy and scanning transmission X-ray microscopy (STXM). At an Fe/C molar ratio ≥ 0.3, both the sorption and co-precipitation immobilized the majority of Cr(III), but the co-precipitation desorbed less Cr(III) than the sorption regardless of DOC loadings and sources. In contrast, Cr(III) immobilization was significantly reduced at an Fe/C molar ratio of 0.1 for both reactions. Linear combination fitting of Cr K-edge XANES spectra revealed the predominance of ferrihydrite-bound Cr(III), but enhanced organic Cr(III) occurred with increased organic carbon (OC) loading for both the sorption and co-precipitation. STXM coupled with multi-edge XANES analysis confirmed the primary association of Cr(III) with ferrihydrite and directly probed carboxyl as the binding site for Cr(III) retention on the OC constituents of the OFC. These results provided new molecular-level insights into the Cr(III) retention mechanisms on the OFC, particularly for the interactions of Cr(III) and OC constituents of the OFC, which could benefit the management of Cr-contaminated soils with straw returning.

16.
BMC Plant Biol ; 20(1): 102, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32138654

RESUMO

BACKGROUND: Brassinolide (BR), as a new type of plant hormones, is involved in the processes of plant growth and stress response. Previous studies have reported the roles of BR in regulating plant developmental processes and also response tolerance to abiotic stresses in plants. The main purpose of our study was to explore whether nitric oxide (NO) plays a role in the process of BR-induced adventitious root formation in cucumber (Cucumis sativus L.). RESULTS: Exogenous application of 1 µM BR significantly promoted adventitious rooting, while high concentrations of BR (2-8 µM) effectively inhibited adventitious rooting. NO donor (S-nitroso-N-acerylpenicillamine, SNAP) promoted the occurrence of adventitious roots. Simultaneously, BR and SNAP applied together significantly promoted adventitious rooting and the combined effect was superior to the application of BR or SNAP alone. Moreover, NO scavenger (c-PTIO) and inhibitors (L-NAME and Tungstate) inhibited the positive effects of BR on adventitious rooting. BR at 1 µM also increased endogenous NO content, NO synthase (NOS-like) and Nitrate reductase (NR) activities, while BRz (a specific BR biosynthesis inhibitor) decreased these effects. In addition, the relative expression level of NR was up-regulated by BR and SNAP, whereas BRz down-regulated it. The application of NO inhibitor (Tungstate) in BR also inhibited the up-regulation of NR. CONCLUSION: BR promoted the formation of adventitious roots by inducing the production of endogenous NO in cucumber.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32033012

RESUMO

Social conflicts occur frequently duringthe social transition period and the polarization of public opinion happens occasionally. By introducing the social preference theory, the target of this paper is to reveal the micro-interaction mechanism of public opinion polarization. Firstly, we divide the social preferences of Internet users (network nodes) into three categories: egoistic, altruistic, and fair preferences, and adopt the revenue function to define the benefits obtained by individuals with different preferences among their interaction process so as to analyze their decision-making behaviors driven by the revenue. Secondly, the revenue function is used to judge the exit rules of nodes in a network, and then a dynamic network of spreading public opinionwith the node (individual) exit mechanism is built based on a BA scale-free network. Subsequently, the influences of different social preferences,as well as individual revenue on the effect of public opinionpolarization, are analyzed through simulation experiments. The simulation results show that(1) Different social preferences demonstrate different influences on the evolution of public opinions, (2) Individuals tend to interact with ones with different preferences, (3) The network with a single preference or a high aggregation is more likely to form public opinion polarization. Finally, the practicability and effectiveness of the proposed model are verified by a real case.

18.
Aging (Albany NY) ; 12(3): 2471-2484, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019903

RESUMO

Patients who suffer sepsis often develop cognitive impairments, yet the underlying mechanisms largely remain to be elucidated. Increasing evidence has suggested that parvalbumin (PV) interneurons are required for the synchronization of neural activities and higher brain processes, whereas its dysfunction is implicated in many psychiatric disorders. In the present study, we examined the role of hippocampal PV interneuron-mediated inhibitory network in a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP) and also explored the underlying mechanism. Here we showed that CLP-induced cognitive impairments, which were accompanied by significantly decreased expressions of PV and dopamine 4 (D4) receptor, decreased slow γ oscillation band, and reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs). Notably, D4 receptor agonist RO-10-5824 treatment was able to reverse most of these abnormities. In summary, our study suggests that sepsis might disrupt PV interneuron-mediated network function that is dependent on the D4 receptor, leading to abnormal γ oscillation and consequent cognitive impairments.

19.
J Sci Food Agric ; 100(8): 3308-3318, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32108348

RESUMO

BACKGROUND: Probiotics are defined as microorganisms that can exert health benefits for the host. Among the recognized probiotics, Bifidobacterium are the most frequently used probiotics in humans. The aim of this study was to evaluate the antidiabetic activity of Bifidobacterium strains isolated from breastfed infant faeces, both in vitro, using the Caco-2 monolayer transwell model, and in vivo, using a mice model of impaired glucose tolerance induced by a high-fat diet (HFD). RESULTS: The cell-free supernatant of Bifidobacterium lactis A12 showed better inhibitory activity of α-glucosidase and inhibited the glucose absorption and transport than B. lactis BB12, which is a typical probiotic with antidiabetic capabilities. B. lactis A12 improved the impaired glucose intolerance, restored islet function and morphology with insulin resistance induced by the HFD in C57BL/6J mice. Furthermore, in small intestine tissues, the cell-free supernatant of B. lactis A12 decreased the messenger RNA expressions of sucrase-isomaltase, live B. lactis A12 cells decreased glucose transporters 2. B. lactis A12 significantly stimulated the glucagon like peptide-1 (GLP-1) secretion and upregulated proglucagon messenger RNA levels. CONCLUSION: B. lactis A12 protect against the deleterious effects of HFD-induced diabetes by inhibiting the utilization, absorption, and transport of glucose by intestinal epithelial cells and promoting the expression and secretion of GLP-1. © 2020 Society of Chemical Industry.

20.
Life Sci ; 247: 117359, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001264

RESUMO

AIMS: Dexmedetomidine (DEX) is a selective agonist of α2-adrenergic receptors with anesthetic attributes and neuroprotective effects. This study was designed to explore the mechanisms of DEX in the propofol-induced neuronal injury in rat hippocampus. MATERIALS AND METHODS: Rat hippocampi were treated with propofol, and then neuronal injury, neuronal apoptosis, PSD95 and apoptosis-related protein expression in CA1 region were measured after DEX administration and/or ant-miR-34a. miR-34a expression was detected using RT-qPCR, while the binding of miR-34a and Sirtuin1 (SIRT1) was identified with dual luciferase reporter gene assay, and the activation of PI3K/Akt signaling pathway was detected. Additionally, hippocampal neurons were cultured in vitro and treated with DEX and propofol. The viability and apoptosis of hippocampal neurons, fluorescence intensity of Ca2+ and neuronal morphology were detected. KEY FINDINGS: In vivo experiments, propofol induced obvious neuronal injury in rat hippocampus, while DEX at different doses reduced hippocampal neuronal apoptosis and miR-34a expression but increased PSD95 expression in rat hippocampus. Low expression of miR-34a reduced propofol-induced neuronal injury by targeting SIRT1 and activating the PI3K/Akt pathway. In vitro experiments, propofol induced neuronal injury, which was alleviated by DEX treatment, accompanied with increased neuronal viability, but decreased apoptosis and fluorescence intensity of Ca2+. The attenuation of neuronal injury achieved by DEX was impaired by over-expression of miR-34a. Meanwhile, over-expression of SIRT1 in neurons with overexpressed miR-34a improved p-Akt and p-PI3K expression. SIGNIFICANCE: DEX could inhibit propofol-induced neuronal injury in rat hippocampus by inhibiting miR-34a expression, upregulating SIRT1 and activating the PI3K/Akt pathway.


Assuntos
Dexmedetomidina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs , Propofol/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuína 1/metabolismo
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