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1.
Rev Sci Instrum ; 92(10): 105106, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717391

RESUMO

To propose a new method for real-time monitoring of blood pressure of blood loss (BPBL), this article combines pulse transit time (PTT) and heart rate variability (HRV) as input parameters to build a model for BPBL estimation. In this article, effective parameters such as PTT, R-R interval (RRI), and HRV were extracted and used to establish the blood pressure (BP) estimation. Three BP estimation models were created: the PTT model, the RRI model, and the HRV model, and they were divided into an experimental group and a control group. Finally, the effects of the different estimation models on the accuracy of BPBL were evaluated using the experimental results. The result showed that both the RRI model and the HRV model have a good improvement effect on the prediction accuracy of BPBL, and the HRV model has the highest prediction accuracy than the PTT model and the RRI model. The correlation coefficients between the actual systolic BP (SBP) and diastolic BP (DBP) and the estimated SBP and DBP of the HRV model were 0.9580 and 0.9749, respectively, and the root-mean-square error of the HRV model for both SBP and DBP were 7.59 and 6.56 mmHg, respectively. The results suggest that the accuracy of the BPBL estimated by the HRV models is better than that of the PTT model, which means that HRV seems to be more effective in improving the accuracy of BP estimation compared with RRI. These results in this article provide a new idea for other researchers in the field of BPBL estimation research.


Assuntos
Determinação da Pressão Arterial , Fotopletismografia , Pressão Sanguínea , Frequência Cardíaca , Análise de Onda de Pulso
2.
Comput Methods Programs Biomed ; 141: 111-117, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28241962

RESUMO

In recent years, numerous adaptive filtering techniques have been developed to suppress the chest compression (CC) artifact for reliable analysis of the electrocardiogram (ECG) rhythm without CC interruption. Unfortunately, the result of rhythm diagnosis during CCs is still unsatisfactory in many studies. The misclassification between corrupted asystole (ASY) and corrupted ventricular fibrillation (VF) is generally regarded as one of the major reasons for the poor performance of reported methods. In order to improve the diagnosis of VF/ASY corrupted by CCs, a novel method combining a least mean-square (LMS) filter and an amplitude spectrum area (AMSA) analysis was developed based only on the analysis of the surface of the corrupted ECG episode. This method was tested on 253 VF and 160 ASY ECG samples from subjects who experienced cardiac arrest using a porcine model and was compared with six other algorithms. The validation results indicated that this method, which yielded a satisfactory result with a sensitivity of 93.3%, a specificity of 96.3% and an accuracy of 94.8%, is superior to the other reported techniques. After improvement using the human ECG records in real cardiopulmonary resuscitation (CPR) scenarios, the algorithm is promising for corrupted VF/ASY detection with no hardware alterations in clinical practice.


Assuntos
Reanimação Cardiopulmonar , Eletrocardiografia , Parada Cardíaca/diagnóstico , Fibrilação Ventricular/diagnóstico , Animais , Artefatos , Diagnóstico Diferencial , Suínos
3.
J Int Med Res ; 44(6): 1331-1338, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27856935

RESUMO

Objective To determine the expression and clinical significance of plasma miR-335 in patients with acute ischemic stroke (AIS) and investigate its association with calmodulin (CaM) expression. Methods Plasma miR-335 and CaM expression levels in patients with AIS and healthy controls were examined. Correlations between miR-335, CaM, and National Institutes of Health Stroke Scale scores were also analysed. Furthermore, the potential regulatory function of miR-335 on CaM expression was investigated. Results Plasma miR-335 levels were significantly lower in AIS and negatively correlated with NIHSS scores. The converse was observed for plasma CaM levels. Plasma miR-335 and CaM levels were negatively correlated. Plasma miR-335 was confirmed as a novel biomarker for AIS diagnosis and an independent predictor of AIS. Up-regulation of miR-335 suppressed CaM protein expression, and CaM was confirmed as a direct target of miR-335. Conclusions Plasma miR-335 was down-regulated in AIS patients and represents a potential noninvasive circulating biomarker.


Assuntos
Isquemia Encefálica/genética , Calmodulina/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Acidente Vascular Cerebral/genética , Idoso , Sequência de Bases , Sítios de Ligação , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Calmodulina/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Transdução de Sinais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/patologia
4.
Prog Biophys Mol Biol ; 122(2): 140-148, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27666961

RESUMO

Casein kinase 2-interacting protein 1 (CKIP-1) is a negative regulator for bone formation. CKIP-1 knockout (KO) mice are very important for research on countermeasures to bone loss induced by space microgravity. Under simulated microgravity, the bone metabolism of CKIP-1 KO mice was different than that of wild-type (WT) mice. Many experiments all showed that the KO mice had significantly enhanced ossification in the tail suspension conditions, and the differences were closely related to the time the mice were exposed to the microgravity environment. Our results reveal the effect of CKIP-1 on the regulation of bone metabolism and osteogenesis in vivo and the ability of this gene to offset osteoporosis, and they suggest an approach to the treatment of osteoporosis induced by microgravity in space.


Assuntos
Proteínas de Transporte/genética , Técnicas de Inativação de Genes , Osteoporose/etiologia , Osteoporose/metabolismo , Simulação de Ausência de Peso/efeitos adversos , Fosfatase Alcalina/sangue , Animais , Fenômenos Biomecânicos , Proteínas de Transporte/metabolismo , Diferenciação Celular , Colágeno Tipo I/metabolismo , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Fêmur/patologia , Fêmur/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Osteocalcina/sangue , Osteogênese , Osteoporose/genética , Osteoporose/fisiopatologia , Microtomografia por Raio-X
5.
Australas Phys Eng Sci Med ; 39(2): 391-401, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26831488

RESUMO

Ventricular fibrillation (VF) is observed as the initial rhythm in the majority of patients suffering from sudden cardiac arrest. It is vitally important to accurately recognize the initial VF rhythm and then implement electrical defibrillation. However, artifacts produced by chest compression during cardiopulmonary resuscitation (CPR) make the VF detection algorithms utilized by current automated external defibrillators (AEDs) unreliable. CPR must be traditionally interrupted for a reliable diagnosis. However, interruptions in chest compression have a deleterious effect on the success of defibrillation. The elimination of the CPR artifacts would enable compressions to continue during AED VF detection and thereby increase the likelihood of resuscitation success. We have estimated a model of this artifact by adaptively incorporating noise-assisted multivariate empirical mode decomposition (NA-MEMD) and least mean squares (LMS) and then removing the artifact from the corrupted ECGs. The simulation experiment indicated that the CPR artifact could be accurately modeled without any reference channels. We constructed a BP neural network to evaluate the results. A total of 372 VF and 645 normal sinus rhythm (SR) ECG samples were included in the analysis, and 24 CPR artifact signals were used to construct corrupted ECGs. The results indicated that at different SNR levels ranging from 0 to -12 dB, the sensitivity and specificity were always above 95 and 80 %, respectively.


Assuntos
Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/normas , Fibrilação Ventricular/diagnóstico , Algoritmos , Artefatos , Eletrocardiografia , Humanos , Redes Neurais de Computação , Curva ROC , Padrões de Referência , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Razão Sinal-Ruído , Fatores de Tempo
6.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 33(4): 747-54, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29714916

RESUMO

On account of the mechanical disturbance of external chest pressing to electrocardiogram(ECG)signal,the ECG rhythm cannot be identified reliably during the cardio-pulmonary resuscitation period.Whereas the possibility of successful resuscitation will be lowered due to interrupted external chest pressing,a new filtering algorithm,enhanced leastmean-square(eLMS)algorithm,was proposed and developed in our laboratory.The algorithm can filter the disturbance of external chest pressing without the support of hardware reference signal and correctly identify ventricular fibrillation(VF)rhythm and normal sinus rhythm in case of uninterrupted external chest pressing.Without other reference signals,this algorithm realizes filtering only through the interrupted electrocardiograma(cECG)signal.It was verified with ECG signal and disturbance signal under different signal to noise ratios and contrasted with other mature algorithms.The verification results showed that the identification effect of eLMS was superior to those of others under different signal to noise ratios.Furthermore,ECG rhythm can be correctly identified only through cECG signal.This algorithm not only reduces the research and development(R&D)costs of automated external defibrillator but also raises the identification accuracy of ECG rhythm and the possibility of successful resuscitation.


Assuntos
Algoritmos , Reanimação Cardiopulmonar , Eletrocardiografia , Fibrilação Ventricular/diagnóstico , Artefatos , Desfibriladores , Parada Cardíaca/terapia , Humanos , Pressão , Razão Sinal-Ruído , Fibrilação Ventricular/fisiopatologia
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 35(7): 1076-8, 1 p following 1078, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26198966

RESUMO

OBJECTIVE: To observe the effects of anesthetic intervention with small-dose lidocaine and ketamine on early postoperative cognitive function in elderly patients undergoing surgeries for gastrointestinal tumors. METHODS: Sixty patients (ASA I-III, aged 63-82 years) scheduled for surgeries for gastrointestinal tumors were randomized into intervention group (n=30) and control group (n=30). After intravenous induction and tracheal intubation, the patients in the interventional group received intravenous infusion of 0.5 mg/kg lidocaine and 0.5 mg/kg ketamine, followed by continuous infusion of lidocaine at the rate of 0.5 mg·kg(-1)·h(-1) till the end of the operation; the patients in the control group received saline infusion only. The cognitive function of the patients was assessed at 3 day before and 2 day after the operation using comprehensive neuro-psychological tests. Peripheral venous blood was extracted before anesthesia induction (T0), at the end of the surgery (T1), and at 1 day (T2) and 2 days (T3) after the operation for measurement of serum S-100ß protein, NSE and IL-6 levels using ELISA. RESULTS: The difference between the test scores before and after the operation (X values) was significantly smaller in the intervention group than in the control group (P<0.05). The intervention group showed a significantly lower incidence rate of postoperative cognitive dysfunction (POCD) than the control group (6.7% vs 33.3%, P<0.05). Compared with the control group, the intervention group exhibited significantly lower serum levels of S-100ß protein, NSE and IL-6 at T1 (P<0.05), significantly lower NSE and IL-6 levels at T2 (P<0.05) time point, and significantly lower IL-6 level at T3 (P<0.05). CONCLUSION: Intravenous injection of small-dose lidocaine and ketamine during the operation can reduce the incidence of POCD in elderly patients undergoing surgeries for gastrointestinal tumors possibly in relation to decreased serum S-100ß, NSE and IL-6 levels.


Assuntos
Cognição/efeitos dos fármacos , Neoplasias Gastrointestinais/cirurgia , Ketamina/uso terapêutico , Lidocaína/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anestésicos/uso terapêutico , Humanos , Interleucina-6/sangue , Complicações Pós-Operatórias , Período Pós-Operatório , Subunidade beta da Proteína Ligante de Cálcio S100/sangue
8.
Int J Med Sci ; 10(13): 1837-45, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24324360

RESUMO

BACKGROUND: In heart, the extracellular matrix (ECM), produced by cardiac fibroblasts, is a potent regulator of heart's function and growth, and provides a supportive scaffold for heart cells in vitro and in vivo. Cardiac fibroblasts are subjected to mechanical loading all the time in vivo. Therefore, the influences of mechanical loading on formation and bioactivity of cardiac fibroblasts ECM should be investigated. METHODS: Rat cardiac fibroblasts were cultured on silicone elastic membranes and stimulated with mechanical cyclic stretch. After removing the cells, the ECMs coated on the membranes were prepared, some ECMs were treated with heparinase II (GAG-lyase), then the collagen, glycosaminoglycan (GAG) and ECM proteins were assayed. Isolated neonatal rat ventricular cells were seeded on ECM-coated membranes, the viability and lactate dehydrogenase (LDH) activity of the cells after 1-7 days of culture was assayed. In addition, the ATPase activity and related protein level, glucose consumption ratio and lactic acid production ratio of the ventricular cells were analyzed by spectrophotometric methods and Western blot. RESULTS: The cyclic stretch increased collagen and GAG levels of the ECMs, and elevated protein levels of collagen I and fibronectin. Compared with the ECMs produced by unstretched cardiac fibroblasts, the ECMs of mechanically stretched fibroblasts improved viability and LDH activity, elevated the Na⁺/K⁺-ATPase activity, sarco(endo)plasmic reticulum Ca²âº-ATPase (SERCA) activity and SERCA 2a protein level, glucose consumption ratio and lactic acid production ratio of ventricular cells seeded on them. The treatment with heparinase II reduced GAG levels of these ECMs, and lowered these metabolism-related indices of ventricular cells cultured on the ECMs. CONCLUSIONS: Mechanical stretch promotes ECM formation of cardiac fibroblasts in vitro, the ECM of mechanically stretched cardiac fibroblasts improves metabolic activity of ventricular cells cultured in vitro, and the GAG of the ECMs is involved in regulating metabolic activity of ventricular cells.


Assuntos
Matriz Extracelular , Ventrículos do Coração/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Mecânico , Adenosina Trifosfatases/metabolismo , Animais , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/enzimologia , Fibroblastos/metabolismo , Glucose/metabolismo , Ventrículos do Coração/citologia , Ventrículos do Coração/enzimologia , Heparina Liase/metabolismo , L-Lactato Desidrogenase/metabolismo , Ácido Láctico/biossíntese , Miócitos Cardíacos/citologia , Miócitos Cardíacos/enzimologia , Ratos
9.
Ann Biomed Eng ; 41(10): 2056-66, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23609024

RESUMO

Bone remodeling is strictly mediated by the coupled activities of osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively. Although many papers have been published on the mechanical responses of osteoblasts and osteoclasts, little is known about their communication during mechanical loading. In this study, a novel co-culture system was first established using Transwell culture inserts; MC3T3-E1 cells were embedded in the lower compartment of the inserts, and RAW264.7 cells were co-cultured in the upper compartment. The MC3T3-E1 cells were subjected to a mechanical strain of 2500 µÎµ at 0.5 Hz to investigate the effect of strain-loaded osteoblasts on co-cultured osteoclasts. The results showed that osteoblast-like cells were activated with an increase of alkaline phosphatase (ALP) activities. The strain-conditioned medium caused decreased activity of tartrate-resistant acid phosphatase and reduced the number of mature multinucleated osteoclasts, which subsequently resulted in the suppressed formation of resorption pits. The expression levels of cathepsin-K and matrix metalloproteinase-9 were also depressed by the strain-conditioned medium. In addition, we found that the expression ratio between osteoprotegerin (OPG) and receptor activator of NF-kB ligand in osteoblasts was significantly up-regulated due to the enhanced levels of OPG. In summary, we conclude that the strain-stimulated osteoblasts inhibited the differentiation and bone resorption of osteoclasts and that the mechanism was associated with the increased secretion of OPG in osteoblasts.


Assuntos
Reabsorção Óssea , Diferenciação Celular , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Estresse Fisiológico , Animais , Antígenos de Diferenciação/biossíntese , Linhagem Celular , Técnicas de Cocultura , Camundongos , Osteoblastos/citologia , Osteoclastos/citologia , Estresse Mecânico
10.
J Biomech ; 46(7): 1242-7, 2013 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-23540725

RESUMO

In recent years, dynamic mechanical loading has been shown to effectively enhance bone remodeling. The current study attempted to research the counter-effect of constrained dynamic loading on osteoporosis (OP) in ovariectomized (OVX) mice. Female Kunming (KM) mice were randomly divided into 2 groups: SHAM and OVX. The right ulnas of the OVX mice were subjected to a 4-week constrained dynamic loading protocol, and the mechanical properties, trabecular micromorphology parameters and biochemical indices of osteogenesis were evaluated. We detected higher levels of tissue alkaline phosphatase (AKP) and serum bone gamma-carboxyglutamic-acid-containing proteins (BGPs), better trabecular micromorphology parameters and ulnar mechanical properties in the loading group than in the nonloading group. In summary, constrained dynamic loading could prevent ovariectomy-induced osteoporosis by facilitating osteogenesis, improving trabecular microstructure and enhancing bone mechanical properties.


Assuntos
Fosfatase Alcalina/metabolismo , Osso e Ossos , Osteocalcina/metabolismo , Osteogênese , Osteoporose , Animais , Biomarcadores/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Feminino , Camundongos , Osteoporose/metabolismo , Osteoporose/patologia , Osteoporose/fisiopatologia , Ovariectomia , Suporte de Carga
11.
Chin Med Sci J ; 28(4): 218-24, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24382223

RESUMO

OBJECTIVES: To construct the cancellous bone explant model and a method of culturing these bone tissues in vitro, and to investigate the effect of mechanical load on growth of cancellous bone tissue in vitro. METHODS: Cancellous bone were extracted from rabbit femoral head and cut into 1-mm-thick and 8-mm-diameter slices under sterile conditions. HE staining and scanning electron microscopy were employed to identify the histomorphology of the model after being cultured with a new dynamic load and circulating perfusion bioreactor system for 0, 3, 5, and 7 days, respectively. We built a three-dimensional model using microCT and analyzed the loading effects using finite element analysis. The model was subjected to mechanical load of 1000, 2000, 3000, and 4000 µÎµ respectively for 30 minutes per day. After 5 days of continuous stimuli, the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) were detected. Apoptosis was analyzed by DNA ladder detection and caspase-3/8/9 activity detection. RESULTS: After being cultured for 3, 5, and 7 days, the bone explant model grew well. HE staining showed the apparent nucleus in cells at the each indicated time, and electron microscope revealed the living cells in the bone tissue. The activities of AKP and TRAP in the bone explant model under mechanical load of 3000 and 4000 µÎµ were significantly lower than those in the unstressed bone tissues (all P<0.05). DNA ladders were seen in the bone tissue under 3000 and 4000 µÎµ mechanical load. Moreover, there was significant enhancement in the activities of caspase-3/8/9 in the mechanical stress group of 3000 and 4000 µÎµ(all P<0.05). CONCLUSIONS: The cancellous bone explant model extracted from the rabbit femoral head could be alive at least for 7 days in the dynamic load and circulating perfusion bioreactor system, however, pathological mechanical load could affect the bone tissue growth by apoptosis in vitro. The differentiation of osteoblasts and osteoclasts might be inhibited after the model is stimulated by mechanical load of 3000 and 4000 µÎµ.


Assuntos
Desenvolvimento Ósseo , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Apoptose , Caspases/metabolismo , Análise de Elementos Finitos , Isoenzimas/metabolismo , Masculino , Coelhos , Estresse Mecânico , Fosfatase Ácida Resistente a Tartarato , Microtomografia por Raio-X
12.
Acta Biochim Biophys Sin (Shanghai) ; 44(8): 669-77, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22728916

RESUMO

Pre-osteoblast MC3T3-E1 cells were cultured in hyaluronic acid-modified chitosan/collagen/nano-hydroxyapatite (HA-CS/Col/nHAP) composite scaffolds and treated with phytoestrogen α-zearalanol (α-ZAL) to improve bone tissue formation for bone tissue engineering. Perfusion and dynamic strain were applied to three-dimensional (3D) cultured cells, which simulates mechanical microenvironment in bone tissue and solves mass transfer issues. The morphology of cell-scaffold constructs in vitro was then examined and markers of osteogenesis were assessed by immunohistochemistry staining and western blotting. The results showed that cells expanded their pseudopodia in an irregular manner and dispersed along the walls in 3D-dynamic culture. Osteogenic phenotype was increased or maintained by enhanced collagen I (COLI) levels, decreased osteopontin expression and having little effect on osteocalcin expression during the 12 days of in vitro culture. In response to α-ZAL, the cell-scaffold constructs showed inhibited cellular proliferation, enhanced the alkaline phosphatase (ALP) activity and increased ratio of osteoprotegerin to receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). Application of perfusion and dynamic strain to cells-scaffold constructs treated with α-ZAL represents a promising approach in the studies of osteogenesis stimulation of bone tissue engineering.


Assuntos
Osteoblastos/citologia , Zeranol/farmacologia , Células 3T3 , Animais , Osso e Ossos/metabolismo , Técnicas de Cultura de Células/métodos , Quitosana/química , Colágeno/química , Durapatita/química , Camundongos , Nanoestruturas/química , Osteogênese , Fenótipo , Ligante RANK/metabolismo , Estresse Mecânico , Engenharia Tecidual/métodos , Alicerces Teciduais
13.
Ann Biomed Eng ; 40(9): 1884-94, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22441665

RESUMO

Bone morphogenetic proteins (BMPs) are known to be important in osteoblasts' response to mechanical stimuli. BMPs/Smad signaling pathway has been demonstrated to play a regulatory role in the mechanical signal transduction in osteoblasts. However, little is currently known about the Smad independent pathway in osteoblasts differentiation in mechanical loading. In this study, MC3T3-E1 cells were subjected to mechanical stretch of 2000 micro-stain (µÎµ) at 0.5 Hz, in order to investigate the involvement of p38MAPK and NF-κB signaling pathways in mechanical response in osteoblasts. We found BMP-2/BMP-4 were up-regulated by mechanical stretch via the earlier activation of p38MAPK and NF-κB signaling pathways, which enhanced osteogenic gene expressions including alkaline phosphatase (ALP), collagen type I (Col I) and osteocalcin (OCN), and the expressions of these osteogenic genes were remarkably decreased with Noggin (an inhibitor for BMPs signals) pretreatment. Furthermore, BMP-2/BMP-4 expressions were suppressed by PDTC, an inhibitor of NF-κB pathway and SB203580, an inhibitor of p38MAPK pathway, respectively, leading to the declined levels of ALP, Col I and OCN. Interestingly, blocking in p38MAPK pathway can also cause the inactivation of NF-κB pathway in mechanical stretch. Collectively, the results indicate during mechanical stretch p38MAPK and NF-κB signaling pathways are activated first, and then up-regulate BMP-2/BMP-4 to enhance osteogenic gene expressions. Moreover, p38MAPK and NF-κB signals have cross-talk in regulation of BMP-2/BMP-4 in mechanical response.


Assuntos
Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 4/genética , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Estresse Mecânico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Células 3T3 , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/metabolismo , Diferenciação Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Regulação da Expressão Gênica , Camundongos , Osteoblastos/citologia , Osteocalcina/genética , Osteocalcina/metabolismo , RNA Mensageiro/metabolismo
14.
Zhongguo Zhong Yao Za Zhi ; 34(23): 3082-6, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20222429

RESUMO

OBJECTIVE: To study the effect of geniposide-acid(GA) on the anti-inflammatory action for adjuvant-induced arthritis (AA) rats and the proliferation of synoviocytes in AA rats and the feasible mechanism of apoptosis in vitro. METHOD: Forty-eight health male Wistar rats were divided randomly into six groups and were administered respectively with 200, 100, 50 mg x kg(-1) GA and 0.75 mg x kg(-1) MTX and normal sodium (normal or model control group) for four weeks when right posterior paw pads of rats excluding normal control group were injected intrademally with complete Freund's adjuvant after 19 days. The left posterior paws swelling degree, swelling inhibition ratio and arthritis index of secondary inflamation were detected. The TNF-alpha and IL-1beta proteins in serum of rats were assayed by enzyme linked immunosorbent assay (ELISA) kits. The synovial fibroblasts of AA rats were exposed to 1-4 micromol x L(-1) GA or 4 micromol x L(-1) MTX. The effect of GA on the proliferation of synoviocytes was detected by MTT assay. The morphologic change of apoptosis cells was observed by Hoechst/PI double stainning and fluorescence microscope. The rate of apoptosis cells was analyzed by flow cytometry. The mRNA expresstion of Bcl-2 and Bax gene was detected by reverse transcription PCR (RT-PCR). RESULT: 200 mg kg(-1) or 100 mg kg(-1) GA could decrease significantly the paw swelling degree, arthritis index and the level of TNF-alpha and IL-1beta proteins in serum of AA rats (P < 0.05 or P < 0.01) with 25.4%, 21.37% of the swelling inhibition ratio respectivly, 34.61%, 28% of protein inhibition ratio of TNF-alpha and 29.05%, 21.65% of that of IL-1beta. GA(1-4 micromol x L(-1)) inhibitated significantly the proliferation of synoviocytes culcured for 5 days. Flow cytometry showed that 1, 2, 4 micromol x L(-1) GA increased obviously the rate of apoptosis cells, the apoptosis ratios were 15.8%, 24.3%, 40.7% respectivly (P < 0.01). RT-PCR showed GA could decrease the expression level of Bcl-2 gene but increase that of Bax gene (P < 0.05 or P < 0.01). CONCLUSION: GA could inhibit the secondary inflamation of AA rats and decrease the level of TNF-alpha and IL-1beta protein in the AA rats serum. GA could inhibit the proliferation of AA rat synoviocytes in vitro and induce apoptosis which mechanism was concerned with down-regulating the mRNA expression of Bcl-2 and up-regulating that of Bax.


Assuntos
Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Glucosídeos/administração & dosagem , Iridoides/administração & dosagem , Líquido Sinovial/citologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Artrite Experimental/fisiopatologia , Citocinas/imunologia , Modelos Animais de Doenças , Adjuvante de Freund/efeitos adversos , Humanos , Glucosídeos Iridoides , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/imunologia
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