RESUMO
Objective: Chronic pulmonary inflammation caused by long-term smoking is the core pathology of COPD. Alveolar macrophages (AMs) are involved in the pulmonary inflammation of COPD. The accumulation of damaged materials caused by impaired autophagy triggers inflammatory response in macrophages. As a key transcription regulator, transcription factor EB (TFEB) activates the transcription of target genes related autophagy and lysosome by binding to promoters, whereas it is unclarified for the relationship between inflammatory response induced by cigarette smoke extract (CSE) and TFEB-mediated autophagy. Thus, we investigated the role of TFEB-mediated autophagy in inflammatory response induced by CSE in NR8383 cells, and to explore its potential mechanism. Methods: Based on cell viability and autophagy, cells treated with 20% concentration of CSE for 24 h were selected for further studies. Cells were divided into control group, chloroquine (CQ, the autophagy inhibitor) group, CSE group, CSE + rapamycin (the autophagy inducer) group and CSE + fisetin (the TFEB inducer) group. The levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 in supernatant were detected by ELISA kits. The protein expressions were tested by western blot. The intensity of fluorescence of Lysosome-associated membrane protein 1 (LAMP1) and TFEB was detected by immunofluorescence. Lyso-Tracker Red staining was applied to detect the lysosome environment. Results: CSE inhibited the cell viability, increased the contents of TNF-α, IL-1ß, IL-6, the ratio of LC3II/I, and the level of P62 protein. Besides, CSE decreased the fluorescence intensity of LAMP1 protein and Lyso-Tracker Red staining, as well as the ratio of nucleus/cytosol of TFEB protein. Activating autophagy with rapamycin alleviated CSE-induced inflammatory response. The activation of TFEB via fisetin alleviated CSE-induced autophagy impairment and lysosomal dysfunction, thus alleviated inflammatory response in NR8383 cells. Conclusion: CSE-induced inflammatory response in NR8383 cells, which may be related to the inhibition of TFEB-mediated autophagy.
Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Fumar Cigarros/efeitos adversos , Fator de Necrose Tumoral alfa , Interleucina-6 , Autofagia , NicotianaRESUMO
In this paper, a new dual-training method for a time-delay reservoir computing (RC) system based on a single vertical-cavity surface-emitting laser (VCSEL) is proposed and demonstrated experimentally for the first time. The prediction performance of the RC system by using the dual-training method has been experimentally and numerically investigated. Here, the dual-training method is defined as performing a further RC based on the difference between the target value and the predicted value of the traditional single training. It is found that enhanced prediction performance of the RC system can be obtained by employing the dual-training method, compared to the traditional single training method. More specifically, the NMSE values of the RC system with the dual-training method applied can be improved to 760% compared with the single training method in experiments. Besides, the effects of injection power, bias currents, feedback strength, and frequency detuning are also considered. The proposed dual-training method is of great significance to the performance enhancement of the RC and has an important promotion effect on the application of the RC in the future.
RESUMO
Motion detection and direction recognition are two important fundamental visual functions among the many cognitive functions performed by the human visual system. The retina and visual cortex are indispensable for composing the visual nervous system. The retina is responsible for transmitting electrical signals converted from light signals to the visual cortex of the brain. We propose a photonic spiking neural network (SNN) based on vertical-cavity surface-emitting lasers with an embedding saturable absorber (VCSELs-SA) with temporal integration effects, and demonstrate that the motion detection and direction recognition tasks can be solved by mimicking the visual nervous system. Simulation results reveal that the proposed photonic SNN with a modified supervised algorithm combining the tempotron and the STDP rule can correctly detect the motion and recognize the direction angles, and is robust to time jitter and the current difference between VCSEL-SAs. The proposed approach adopts a low-power photonic neuromorphic system for real-time information processing, which provides theoretical support for the large-scale application of hardware photonic SNN in the future.
Assuntos
Redes Neurais de Computação , Fótons , Humanos , Lasers , Movimento (Física) , Óptica e FotônicaRESUMO
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a respiratory disease with high morbidity and mortality worldwide, so far there is no ideal treatment method. Previous studies have shown that hydrogen (H2) is involved in the treatment of COPD as an antioxidant. In this study, the effect of H2 on M1/M2 polarization of alveolar macrophages in COPD rats was observed, and its anti-inflammatory mechanism was further elucidated. Methods: Twenty-four Sprague-Dawley rats were randomly divided into three groups including the control, COPD and H2 group. A rat model of COPD was established by cigarette exposure combined with lipopolysaccharide (LPS) induction. H2 therapy was administered 2 hours per day for 14 days. Lung function and pathology were assessed. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1 and IL-10 in bronchoalveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA, protein expression and immunoreactivity of inducible nitric oxide synthase (iNOS) and arginase (Arg)-1 in lung were observed by quantitative real-time PCR, western blot and immunohistochemistry. Results: Compared with the control rats, there were a significant decline in lung function, a marked inflammatory infiltration and pulmonary parenchymal remodeling and the increases of IL-6, TNF-α and TGF-ß1 levels in BALF and lung tissue, but a lower expression of IL-10 in COPD rats. The iNOS mRNA and protein expression, as well as its optical density (OD), were increased significantly in lung tissue, while those of Arg-1 decreased significantly. H2 treatment improved the lung function and the parenchymal inflammation, reversed the increased levels of IL-6, TNF-α and TGF-ß1, and the lower IL-10. Meanwhile, H2 also down-regulated the expression of iNOS, but up-regulated expression of Arg-1 in lung tissue. Conclusion: H2 reduces inflammation in the lung of COPD, which may be related to its inhibition of M1 type polarization and activation of M2 type polarization of alveolar macrophage.
Assuntos
Macrófagos Alveolares , Doença Pulmonar Obstrutiva Crônica , Animais , Hidrogênio , Pulmão , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
We propose a photonic spiking neural network (SNN) based on excitable vertical-cavity surface-emitting lasers with an embedded saturable absorber (VCSELs-SA) for emulating the sound azimuth detection function of the brain for the first time. Here, the spike encoding and response properties based on the excitability of VCSELs-SA are employed, and the difference between spike timings of two postsynaptic neurons serves as an indication of sound azimuth. Furthermore, the weight matrix contributing to the successful sound azimuth detection is carefully identified, and the effect of the time interval between two presynaptic spikes is considered. It is found that the weight range that can achieve sound azimuth detection decreases gradually with the increase of the time interval between the sound arriving at the left and right ears. Besides, the effective detection range of the time interval between two presynaptic spikes is also identified, which is similar to that of the biological auditory system, but with a much higher resolution which is at the nanosecond time scale. We further discuss the effect of device variations on the photonic sound azimuth detection. Hence, this photonic SNN is biologically plausible, which has comparable low energy consumption and higher resolution compared with the biological system. This work is valuable for brain-inspired information processing and a promising foundation for more complex spiking information processing implemented by photonic neuromorphic computing systems.
Assuntos
Lasers , Redes Neurais de Computação , Fótons , Som , Propriedades de SuperfícieRESUMO
A novel Four-channels reservoir computing (RC) based on polarization dynamics in mutually coupled vertical cavity surface emitting lasers (MDC-VCSELs) is proposed and demonstrated numerically. Here, the four channels are realized in two orthogonal polarization modes (x-polarization and y-polarization modes) of two VCSELs for the first time. A chaotic time series prediction task is employed to quantitatively evaluated the prediction performance of the proposed system. It is found that the Four-channels RC based on MDC-VCSELs can produce comparable prediction performance with One-channel RC, and it is possible to increase four times information processing rate by using the Four-channels RC. Besides, the effects of injection current, external injection strength, frequency detuning, coupling strength, as well as internal parameters on the prediction performance of the Four-channels RC based on MDC-VCSELs are carefully examined. Moreover, the influences of sampled period of input signal and the number of virtual nodes are also considered. The proposed Four-channels RC based on MDC-VCSELs is valuable for further enhancing the information processing rate of RC-based neuromorphic photonic systems.
RESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Feishu" (BL13) on the activation and secretion of calcitonin gene-related peptide (CGRP) and 5-hydroxytryptamine (5-HT) of pulmonary neuroendocrine cells (PNECs) and inflammatory response in rats with chronic obstructive pulmonary disease (COPD), so as to explore its underlying mechanisms in treating COPD. METHODS: Male SD rats were randomly divided into normal control, COPD model and EA groups, with 7 rats in each group. The COPD model was established by forced inhale of cigarette smoke for 1 h in a self-made box (1 m×1 m×1 m in volume), twice daily for 12 weeks. EA (4 Hz/20 Hz, 1-3 mA) was applied at bilateral ST36 and BL13 acupoints for 30 min, once a day for 14 consecutive days. The pulmonary function including the forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV0.1), FEV0.3, FEV0.1/FVC and FEV0.3/FVC was detected using a lung function analyzer for small animals. The lung tissue was sampled for observing histopathological changes by using H.E. staining, for observing expression and distribution of PNECs by Grimelius silver staining, and for detecting the immunoactivity (integrated optical density) of CGRP and 5-HT by using immunohistochemistry. The contents of CGRP, 5-HT, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and transforming growth factor-ß1 (TGF-ß1) in the bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA, and the correlations between TNF-α and CGRP, IL-1ß and CGRP, TNF-α and 5-HT, and IL-1ß and 5-HT levels were analyzed. The mRNA and protein expression levels of nerve fiber markers of CGRP and purinergic receptor P2X ligand gated ion channel 3 (P2X3) which dominate PNECs in the lung tissue were detected by real-time fluorescence quantitative PCR and Western blot, respectively. RESULTS: Compared with the normal control group, the levels of FVC, FEV0.1, FEV0.3, and the ratios of FEV0.1/FVC and FEV0.3/FVC were significantly decreased (P<0.05, P<0.01), while the immunoactivity of PNECs, CGRP and 5-HT, the contents of CGRP, 5-HT, TNF-α, IL-1ß and TGF-ß1 in the BALF and lung tissue, and the expression levels of CGRP and P2X3 mRNAs and proteins in the lung tissue significantly increased in the COPD model group (P<0.01, P<0.05). Following EA intervention, both the increased and decreased levels of all the indexes mentioned above were reversed (P<0.05, P<0.01) except FEV0.3. H.E. staining showed severe deformed bronchial lumen with thickened wall and alveolar septum, and obvious inflammatory cell infiltration and reduced number of alveolar lumen fusion in the COPD model group, which was mild in the EA group. A positive correlation was found between TNF-α and CGRP, IL-1ß and CGRP, TNF-α and 5-HT,IL-1ß and 5-HT levels in both BALF and lung tissues (P<0.01). CONCLUSION: EA at ST36 and BL13 can improve lung function and reduce inflammatory response in COPD rats, which may be related to its function in inhibiting the activation of PNECs and release of neuroactive substances.
Assuntos
Eletroacupuntura , Células Neuroendócrinas , Doença Pulmonar Obstrutiva Crônica , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Pulmão/metabolismo , Masculino , Células Neuroendócrinas/química , Células Neuroendócrinas/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , Ratos , Ratos Sprague-Dawley , Serotonina , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) pretreatment on lung functions, inflammatory response, and levels of angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) ï¼»Ang (1-7)ï¼½ in rats with sepsis-induced acute lung injury (ALI), so as to explore its mechanisms underlying improvement of ALI. METHODS: Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The sepsis-related ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). Rats of the EA group received EA (4 Hz/20 Hz, 1-3 mA) stimulation at bilateral ST36 for 30 min, once each day, for 7 days before modeling. The lung functions including forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV0.1) and FEV0.3 were detected using a respiratory function detector for small animals at 3 h after modeling. The bronchoalveolar lavage fluid (BALF) was collected for assaying the contents of Ang (1-7), tumor necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß) using ELISA. The lung wet/dry weight (W/D) ratio, FEV0.1/FVC, and FEV0.3/FVC were calculated. The histopathological changes of lung tissues were displayed by hematoxylin-eosin (H.E.) staining. The expression of ACE2 and mitochondrial assembly receptor (MasR) mRNAs and proteins in the lung tissue was detected by fluorescence quantitative real-time PCR and Western blot, separately. RESULTS: Following modeling, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and the expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly decreased (P<0.01), while the level of W/D ratio and TNF-α and IL-1ß contents in the BALF significantly increased (P<0.01) in the model group relevant to the normal group. In comparison with the model group, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly increased (P<0.05, P<0.01), whereas the level of W/D ratio, and TNF-α and IL-1ß contents in the BALF were significantly decreased (P<0.05, P<0.01) in the EA group. H.E. staining showed pulmonary interstitial edema and alveolar septum thickening with severe inflammatory cell infiltration in the model group, which was relatively milder in the EA group. CONCLUSION: EA preconditioning at ST36 can improve pulmonary function in sepsis-related ALI rats, which may be related to its effects in inhibiting inflammatory response and up-regulating ACE2 and MasR expression and Ang (1-7) content in the lung tissue.
Assuntos
Lesão Pulmonar Aguda , Eletroacupuntura , Sepse , Angiotensina I , Enzima de Conversão de Angiotensina 2 , Animais , Lipopolissacarídeos , Pulmão , Masculino , Fragmentos de Peptídeos , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on the expression of epidermal growth factor receptor (EGFR), tumor necrosis factor α(TNF-α) transfer growth factor α(TGF-α), interleukin-8(IL-8), p38 mitogen-activated protein kinases (p38MAPK), mucin-5AC (MUC5AC) and other related factors in chronic obstructive pulmonary disease (COPD) rats, so as to reveal its underlying mechanisms in improving COPD. METHODS: A total of thirty male SD rats were randomly divided into normal control, model and EA groups, with 10 rats in each group. The COPD model was replicated using a combined method of tracheal infusion of lipopolysaccharide (LPS) and forced smoke-inhaling. EA (1-3 mA, 4 Hz/20 Hz) was applied to bilateral ST36 for 30 min, once daily for two consecutive weeks. The lung ventilation activities including the forced vital capacity (FVC) and forced expiratory volume (FEV) at 0.1 and 0.3 s (FEV0.1, FEV0.3) were detected. Histopathological changes of the middle lobe and bronchus of the right lung were observed after H.E. staining. The contents of TGF-α, TNF-α and IL-8 in the serum, bronchoalveolar lavage fluid (BALF) and superior lobe of the right lung were assayed by using ELISA, and the expression levels of EGFR, p38MAPK and MUC5AC proteins (inferior lobe of the left lung) and mRNAs (inferior lobe of the right lung) detected using Western blot, immunohistochemistry (strept avidin-biotin complex, SABC method) and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the FVC, FEV0.1, FEV0.3, FEV0.1/FVC and FEV0.3/FVC levels were significantly decreased (P<0.01), while the contents of TNF-α, TGF-α and IL-8 in the serum, BALF and lung tissues, expression levels of EGFR, p38MAPK and MUC5AC mRNAs and proteins, and the immunoactivity of EGFR, p38MAPK and MUC5AC in the lung tissues were significantly increased in the model group (P<0.01). After EA intervention, the decreased levels of the FVC, FEV0.1, FEV0.3, FEV0.1/FVC and FEV0.3/FVC, and the increased levels of the abovementioned genes and proteins were all reversed in the EA group (P<0.01, P<0.05). After modeling, the bronchial walls were thickened, with enlarged alveolar cavities, fractured alveolar walls, obvious inflammatory cell infiltration, and rich mucus secretion in the lumen, which was relatively milder in the EA group. CONCLUSION: EA of ST36 can improve the ventilation function in COPD rats, which may be associated with its function in down-regulating the levels of TNF-α, TGF-α, IL-8, EGFR, p38MAPK and MUC5AC mRNAs and proteins in the lung tissues, inhibiting EGFR-p38MAPK signaling mediated expression of MUC5AC.
Assuntos
Eletroacupuntura , Doença Pulmonar Obstrutiva Crônica , Animais , Receptores ErbB/genética , Inflamação , Pulmão , Masculino , Mucina-5AC , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/terapia , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Feishu" (BL13) on the expression of autophagy related proteins in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), so as to explore the mechanism of EA underlying improvement of COPD. METHODS: Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The COPD model was established by intratracheal infusion of Lipopolysaccharide (LPS, 1 mg/kg) and exposure in cigarette smoke. EA was applied to bilateral ST36 and BL13 for 30 min, once every other day for 2 weeks. The pulmonary function (forced vital capacity ï¼»FVCï¼½, forced expiratory volume in 0.1 s and 0.3 s ï¼»FEV0.1, FEV0.3ï¼½, FEV0.1/FVC and FEV0.3/FVC) was detected by animal pulmonary function analysis system. Histopathological changes of the airway and lung were displayed by H.E. staining. Autophagosomes in the airway and lung tissues were observed by electron microscope. The expression of AMP activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), Unc-51 like autophagy activating kinase 1(ULK1), autophagy related protein ATG6(Beclin1)mRNAs in lung tissue were examined by quantitative real-time PCR. The expression of AMPK, mTOR, ULK1, Beclin1 and microtubule-associated protein 1 light chain 3 (LC3)proteins in lung tissue were examined by Western blot. The contents of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the broncho alveolar lavage fluid (BALF) were assayed by ELISA. RESULTS: Following modeling, the FVC, FEV0.1, FEV0.3, FEV0.1/FVC and FEV0.3/FVC levels were significantly decreased (P<0.01), the infiltration of inflammatory cells and the increase of autophagosomes were obvious in airway and lung tissue, the mRNA and protein expression of AMPK, ULK1, Beclin1 and the ratio of LC3â ¡/LC3â were increased (P<0.01), while the mRNA and protein expression of mTOR were decreased (P<0.01), the contents of TNF-α and IL-6 in the BALF were increased in the model group compared with the normal group (P<0.01). After EA intervention, all the indexes mentioned above were completely reversed in the EA group relevant to the model group (P<0.01, P<0.05). CONCLUSION: EA at ST36 and BL13 can improve the lung function of COPD rats, which may be related to its effects in inhibiting the autophagy level and reducing the inflammation response in the lung.
Assuntos
Eletroacupuntura , Doença Pulmonar Obstrutiva Crônica , Animais , Proteínas Relacionadas à Autofagia , Pulmão , Masculino , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/terapia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Interleukin (IL)-17, as a T-helper 17 cell (Th17) cytokine, plays a key role in chronic obstructive pulmonary disease (COPD) pathophysiology including chronic inflammation and airway obstruction, which lead to decreased pulmonary function. The aim of this study was to investigate the effect of acupuncture on IL-17, its receptor (IL-17R) and the mitogen-activated protein kinase (MAPK) signaling pathway, in a rat model of COPD. METHODS: The COPD model was induced in Sprague Dawley rats by exposure to cigarette smoke for 12 weeks. The model rats were treated with electroacupuncture (EA) at BL13 and ST36. The lung function and histology of the rats were observed. IL-17, tumor necrosis factor (TNF)-α, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and in plasma. The leukocytes and macrophages in the BALF were counted. The expression levels of IL-17R were assayed in lung tissue by real-time polymerase chain reaction (PCR), western blotting, and immunohistochemistry. MAPK signaling pathway molecules including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)1/2 and p38, and their phosphorylated forms, were observed in the lung by western blotting. RESULTS: Compared with the control group rats, lung function decreased and there was a severe inflammatory infiltration of the pulmonary parenchyma in the COPD rats. EA effectively improved lung function and alleviated the inflammatory infiltration in the lungs of COPD rats. EA also reversed the elevated total leukocyte and macrophage counts, the high levels of IL-17 and TNF-α, and the low IL-10 content in COPD rats. Meanwhile, EA downregulated the increased mRNA and protein expression of IL-17R, and significantly inhibited the elevated levels of phosphorylated JNK, ERK1/2, and p38 in the lungs of COPD rats. CONCLUSION: Our results suggest that the protective effects of acupuncture therapy on the lungs of COPD rats are likely related to inhibition of IL-17/IL-17R and the post-receptor MAPK signaling pathways.
Assuntos
Eletroacupuntura , Sistema de Sinalização das MAP Quinases , Doença Pulmonar Obstrutiva Crônica/terapia , Receptores de Interleucina/sangue , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Humanos , Interleucina-10/sangue , Interleucina-10/líquido cefalorraquidiano , Interleucina-17/sangue , Interleucina-17/líquido cefalorraquidiano , Pulmão/metabolismo , Masculino , Doença Pulmonar Obstrutiva Crônica/sangue , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/líquido cefalorraquidianoRESUMO
Andrographolide (AG), an ingredient extracted from traditional Chinese herbal medicine Andrographis paniculata, has been demonstrated to have potent anti-inflammatory and anti-oxidative stress properties. The purpose of this study was to investigate whether and how AG attenuated CSE-induced mitochondrial dysfunction, inflammation and oxidative stress in RAW 264.7 cells (a mouse macrophages line). The results showed that AG significantly reduced CSE-induced upregulation of pro-inflammatory cytokines (i.e., TNF-α and IL-1ß) in the RAW 264.7 cells. AG inhibited CSE-induced production of reactive oxygen species (ROS) and prevented the reduction of superoxide dismutase (SOD) and glutathione/oxidized glutathione (GSH/GSSG) ratio, indicating the anti-oxidative stress effects of AG in macrophages. AG also improved mitochondrial function and mitochondrial membrane potential. In addition, AG inhibited CSE-induced increase of heme oxygenase (HO)-1, matrix metalloproteinase (MMP)-9 and MMP-12. Moreover, AG increased SIRT1 transcription and expression, suggesting AG inhibits mitochondrial dysfunction, inflammation and oxidative stress via a SIRT1 dependent signaling. We also demonstrated that AG inhibited CSE-induced ERK phosphorylation, and treatment with PD980589, a ERK inhibitor, reversed CSE-induced inflammation and oxidative stress. These results indicated that AG may prevent COPD via the inhibition of SIRT1/ERK signaling pathway, and subsequently inhibition of mitochondrial dysfunction, inflammation, and oxidative stress in macrophages.
Assuntos
Antioxidantes/farmacologia , Diterpenos/farmacologia , Macrófagos/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Sirtuína 1/metabolismo , Animais , Fumar Cigarros/efeitos adversos , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) and "Feishu" (BL 13) on pulmonary function, inflammatory reaction and expression of macrophage migration inhibitory factor (MIF) and its receptor complex CD 74-CD 44, etc. in rats with chronic obstructive pulmonary disease (COPD), so as to explore its mechanism underlying improvement of COPD. METHODS: Thirty male SD rats were randomly divided into normal, model and EA groups (nï¼10 in each group). The COPD model was established by intratracheal infusion of Lipopolysaccharide (LPS, 1 mg/mL) and forced smoke-inhaling. EA was applied to bilateral ST 36 and BL 13 for 30 min, once daily for 7 days. The rat's lung function (forced vital capacity [FVC], forced expiratory capacity ratio ([FEV 0.1/FVC] and [FEV 0.3/FVC]) was detected under anesthesia. Pathological changes of the lung tissue were detected by Hï¼E. staining, and the contents of MIF, tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1 ß) and IL-8 in serum, bronchoalveolar lavage fluid (BALF) and lung tissue were assayed by ELISA. The immunoactivity of CD 74 and CD 44 was detected by immunohistochemistry, and the expression levels of MIF, CD 74, CD 44 and p 38 MAPK mRNAs and proteins were examined by quantitative RT-PCR and Western blot, respectively. RESULTS: Compared with the normal group, the FVC, FEV 0.1, FEV 0.3, FEV 0.1/FVC and FEV 0.3/FVC levels were significantly decreased in the model group (P<0.01). After EA treatment, the FVC, FEV 0.1, FEV 0.3, FEV 0.1/FVC and FEV 0.3/FVC were significantly increased (P<0.01, P<0.05), suggesting an improvement of the pulmonary function after EA. Hï¼E. staining showed that the severity of modeling induced alveolar expansion and inflammatory cell infiltration in the lung tissue was relatively milder in the EA group relevant to the model group. The contents of MIF, TNF-αï¼ IL-1 ß and IL-8 in the serum, BALF and lung tissues were significantly higher in the model group than in the normal group (P<0.01), and significantly down-regulated in the EA group relevant to the model group (P<0.01). The expression levels of MIF, CD 74, CD 44 and p 38 MAPK mRNAs and proteins and the immunoactivity levels of CD 74, CD 44 in the lung tissue were obviously higher in the model group than those in the normal group (P<0.01), and considerably lower in the EA group than those in the model group (P<0.01). There was a positive correlation between p 38 MAPK and MIF in mRNA and protein expression levels (P<0.01). CONCLUSION: EA intervention can improve the pulmonary function in COPD rats, which may be related to its effects in inhibiting inflammatory reaction, and MIF/CD 74-CD 44/p 38 MAPK signaling pathway.
Assuntos
Eletroacupuntura , Doença Pulmonar Obstrutiva Crônica , Animais , Antígenos de Diferenciação de Linfócitos B , Antígenos de Histocompatibilidade Classe II , Receptores de Hialuronatos , Pulmão , Sistema de Sinalização das MAP Quinases , Fatores Inibidores da Migração de Macrófagos , Masculino , Doença Pulmonar Obstrutiva Crônica/terapia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: We have repeatedly demonstrated that electroacupuncture (EA) stimulation of "Shenmen" (HT 7)- "Tongli" (HT 5) segment of the Heart Meridian can improve acute myocardial ischemia (AMI). This study aimed at observing the effect of EA on contents of hippocampal norepinephrine (NE), and interleukin 6 (IL-6), IL-1 ß and tumor necrosis factor- α (TNF-α) in AMI rats, so as to explore its underlying mechanism. METHODS: SD rats were randomly divided into 3 groups: sham operation (sham), model and EA(n=6 rats in each). The anterior descending branch (ADB) of the left coronary artery was occluded to make an AMI model. For rats of the sham group, a surgical suture was simply threaded beneath the ADB without ligation. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Shenmen" (HT 7)- "Tongli" (HT 5) and the middle-point between HT 7 and HT 5 for 30 min, once daily for 3 days. Electrocardiogram (ECG) of the neck-thoracic lead was recorded by using PowerLab 16. The contents of serum creatine kinase (CK), hippocampal IL-6, IL-1 ß and TNF-α were assayed by ELISA. The concentration of NE in hippocampal CA 1 area was detected by microdialysis combined with electrochemical detector. RESULTS: Compared with the sham group, the ECG-ST height, serum CK, hippocampal NE, IL-6, IL-1 ß and TNF-α contents of the CA 1 region were significantly increased in the model group (P<0.001). Whereas, after EA intervention, the serum CK, hippocampal NE, IL-6, IL-1 ß and TNF-α contents were obviously down-regulated relevant to the model group (P<0.05, P<0.001), and the IL-6, IL-1 ß and TNF-α contents were positively correlated with the NE level (P<0.001, P<0.01). CONCLUSION: EA stimulation of the Heart Meridian may improve ischemic myocardial injury in AMI rats, probably by reducing the proinflammatory factors and hippocampal NE.
Assuntos
Eletroacupuntura , Isquemia Miocárdica , Pontos de Acupuntura , Animais , Hipocampo , Interleucina-1beta , Interleucina-6 , Norepinefrina , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: Acupuncture has a definite therapeutic effect on chronic obstructive pulmonary disease (COPD), and the cholinergic anti-inflammatory pathway (CAP) has been shown to be involved in regulation of inflammation. In this study, we investigated whether electro-acupuncture (EA) affects the CAP in COPD. METHODS: Sprague-Dawley rats were induced into COPD through exposure to cigarette smoke combined with lipopolysaccharide. EA treatment was applied at Zusanli (ST36) and Feishu (BL13) points for 30â¯min/d for 7â¯d. Seventy-two rats were randomly divided into six study groups, including normal, normalâ¯+â¯EA, normalâ¯+â¯α-bungarotoxin (α-BGT) (the antagonist of the nicotinic acetylcholine receptor α7 subunit (α7nAChR))â¯+â¯EA, COPD, COPDâ¯+â¯EA, and COPDâ¯+â¯α-BGTâ¯+â¯EA. Lung function, pathology and vagus nerve discharge were tested. The levels of acetylcholine (ACh), acetylcholinesterase (AChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression and immunoreactivity of α7nAChR and its postreceptor inflammation signal pathway, including janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), nuclear factor-κB (NF-κB), were observed by quantitative reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry. RESULTS: Compared with normal rats, there were a significant decline in lung function and discharge of the vagus nerve (Pâ¯<â¯0.01), a marked sign of lung inflammation and an increase of ACh, AChE, IL-6 and TNF-α level in BALF or lung tissue (Pâ¯<â¯0.05, Pâ¯<â¯0.01) and higher expression of α7nAChR, JAK2, STAT3 and NF-κB (Pâ¯<â¯0.05, Pâ¯<â¯0.01) in the COPD rats. In rats receiving EA, the lung function and vagal discharge were enhanced (Pâ¯<â¯0.01), lung inflammation was improved and the levels of ACh, AChE, IL-6 and TNF-α were decreased (Pâ¯<â¯0.01). Further, the expression of α7nAChR, JAK2, STAT3 and NF-κB was downregulated (Pâ¯<â¯0.05, Pâ¯<â¯0.01). However, the above effects of EA were blocked in rats injected with α-BGT (Pâ¯<â¯0.01). CONCLUSION: EA treatment can reduce the lung inflammatory response and improve lung function in COPD, which may be related to its involvement in the regulation of CAP.