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1.
Zhonghua Yan Ke Za Zhi ; 57(12): 922-929, 2021 Dec 11.
Artículo en Chino | MEDLINE | ID: mdl-34865451

RESUMEN

Objective: To investigate the effect of anti-vascular endothelial growth factor (VEGF) therapy on the expression levels of transforming growth factor-beta (TGF-ß) and its related microRNAs in the vitreous of patients with proliferative diabetic retinopathy (PDR). Methods: This cross-sectional study included 67 patients (67 eyes), 38 males and 29 females, aged (54.37±11.70) years, who underwent vitrectomy from June 2020 to February 2021. There were 45 PDR patients (45 eyes), including 29 patients (29 eyes) without anti-VEGF therapy in the disease group and 16 patients (16 eyes) who were admitted at 7 days after anti-VEGF therapy in the treatment group. The other 22 idiopathic macular hole patients (22 eyes) were in the negative control group. The microRNA (hsa-miR-24-3p and hsa-miR-197-3p) levels in the vitreous of 36 patients (12 cases randomly chosen from each group) were detected by quantitative reverse transcription polymerase chain reaction. The levels of TGF-ß and VEGF-A in the vitreous of 67 patients were detected by enzyme-linked immunosorbent assay. Target gene prediction of hsa-miR-24-3p and hsa-miR-197-3p was performed on RNAhybrid, miRanda and TargetScan7.2 databases, and pathway enrichment analyses were conducted for all target mRNAs. One-way ANOVA was used to compare the levels of growth factors and microRNAs among the three groups, and the least significant difference method was used for multiple comparisons between groups. Pearson correlation test was used to analyze the correlation between growth factors and microRNAs. Results: The expression levels of VEGF-A, TGF-ß, hsa-miR-24-3p and hsa-miR-197-3p were (158.15±17.72) pg/ml, (640.47±24.80) pg/ml, 0.81±0.11 and 1.07±0.15 in the control group, (1 047.54±26.61) pg/ml, (3 553.17±92.61) pg/ml, 8.50±2.33 and 12.23±3.38 in the disease group, and (778.10±27.73) pg/ml, (3 376.02±78.83) pg/ml, 4.54±0.67 and 3.90±0.65 in the treatment group, respectively. All indicators were significantly higher in the disease group than those in the control group (F=355.581, 440.538, 7.546 and 7.546; all P<0.05). The expression levels of VEGF-A, hsa-miR-24-3p and hsa-miR-197-3p in the treatment group were significantly lower than those in the disease group (all P<0.05). The concentration of TGF-ß was not statistically significantly lower in the treatment group compared to the disease group. The concentrations of VEGF-A and TGF-ß were significantly positively correlated with the expression levels of hsa-miR-24-3p and hsa-miR-197-3p in the vitreous of randomly chosen 36 patients (r=0.48, 0.51, 0.40 and 0.42; all P<0.05). Pathway enrichment analysis showed that some target mRNAs of hsa-miR-24-3p and hsa-miR-197-3p were involved in VEGF and TGF-ß signal pathways. Conclusions: In the vitreous of patients with PDR, hsa-miR-24-3p and hsa-miR-197-3p were positively related to VEGF-A and TGF-ß, and may be potential risk factors. Anti-VEGF treatment can significantly reduce the expression level of TGF-ß-related microRNAs, namely hsa-miR-24-3p and hsa-miR-197-3p, but cannot effectively reduce the concentration of TGF-ß, suggesting that combined anti-TGF treatment may be beneficial for delaying the progression of PDR. Furthermore, it may be a new research direction of PDR to validate the target mRNAs of hsa-miR-24-3p and hsa-miR-197-3p involved in VEGF and TGF-ß signal pathways. (Chin J Ophthalmol, 2021, 57: 922-929).


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , MicroARNs , Estudios Transversales , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/genética , Femenino , Humanos , Masculino , MicroARNs/genética , Factor de Crecimiento Transformador beta/genética , Vitrectomía
2.
Ann R Coll Surg Engl ; 100(5): e114-e117, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29607721

RESUMEN

Trauma with foreign objects retained within the human body has become a common surgical emergency condition. Traditional surgical methods often involve creating large incisions in soft tissue and may lead to additional complications during wound healing. We have developed a new method of removing foreign bodies from patients' abdomens by using laparoscopy with the help of a novel navigation system that provides accurate positioning. This approach is minimally invasive and simple. This is the first combination of both technologies in this field.


Asunto(s)
Cuerpos Extraños/cirugía , Laparoscopía/métodos , Espacio Retroperitoneal/cirugía , Cirugía Asistida por Computador/métodos , Adulto , Humanos , Masculino , Metales
4.
Genet Mol Res ; 15(2)2016 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-27323194

RESUMEN

Real-time quantitative polymerase chain reaction (RT-qPCR) is usually employed in gene expression studies in veterinary research, including in studies on canine pyometra. Canine pyometra is a common clinical disease in bitches. When using RT-qPCR, internal standards, such as reference genes, are necessary to investigate relative gene expression by quantitative measurements of mRNA levels. The aim of this study was to evaluate the stability of reference genes and select reference genes suitable for canine pyometra studies. We collected 24 bitch uterine tissue samples, including five healthy and 19 pyometra infected samples. These were used to screen the best reference genes of seven candidate genes (18SrRNA, ACTB, B2M, GAPDH, HPRT, RPL13A, and YWHAZ). The method of KH Sadek and the GeNorm, Normfinder, BestKeeper, and RefFinder software were used to evaluate the stability of gene expression in both pyometra and healthy uterine samples. The results showed that the expression stability of the candidate gene in pyometra and healthy tissues differed. We showed that YWHAZ was the best reference gene, which could be used as an accurate internal control gene in canine pyometra studies. To further validate this recommendation, the expression profile of a target gene insulin-like growth factor 1 receptor gene (IGF1R) was investigated. We found that the expression of IGF1R was significantly altered when different reference genes were used. All reference genes identified in the present study will enable more accurate normalization of gene expression data in both pyometra infected and healthy uterine tissues.


Asunto(s)
Marcadores Genéticos , Útero/metabolismo , Animales , Perros , Femenino , Piómetra/genética , Piómetra/veterinaria , Reacción en Cadena en Tiempo Real de la Polimerasa
5.
Eur Rev Med Pharmacol Sci ; 20(7): 1307-14, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27097951

RESUMEN

OBJECTIVE: To use the 3.0T susceptibility-weighted imaging (SWI) for universality analysis of the "swallow tail" appearance in the substantia nigra of non-Parkinson disease and discuss its lack of the value of imaging diagnosis of Parkinson disease (PD). PATIENTS AND METHODS: Take 3.0TMR SWI in 60 PD patients (Group PD) and non-PD volunteers (Group N-PD), on the map of range analyze morphology and number of "swallow tail" appearance in substantia nigra of N-PD group volunteers, and compare the performance image of the corresponding region of the patients in the PD group. RESULTS: After, 15 patients with lesions in the brain stem and significant motion artifacts were excluded. Forty-nine cases of group N-PD (96.08%) had typical "swallow tail" appearance in the bilateral or unilateral substantia nigra compacta posterolateral. All 54 patients with group PD (100%) lacked the "drop" rear elliptical high signal. CONCLUSIONS: On the 3.0T SWI range map, the "swallow tail" appearance is ubiquitous in the substantia nigra of patients with non-PD. The deficiency of the signs has high sensitivity and specificity for PD diagnosis.


Asunto(s)
Imagen por Resonancia Magnética/normas , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Negra/diagnóstico por imagen , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad
6.
Eur Rev Med Pharmacol Sci ; 19(23): 4603-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26698258

RESUMEN

OBJECTIVE: To assess the imaging features of nigrosomes-1 in the substantia nigra through 3T MR susceptibility weighted imaging (SWI) and its disease-specific changes for the diagnosis of Parkinson's disease (PD). PATIENTS AND METHODS: A total of 116 subjects were included in this study and allocated into 3 groups: 54 patients diagnosed with PD were assigned to the PD group, 51 age- and sex-matched volunteers without PD served as the control N-PD group, and 11 clinically suspected PD patients were allocated to the undiagnosed (UD) group. All patients received 3.0T superconducting MRI scanning on xxx. The images were analyzed and compared to assess the ability of nigrosomes-1 signals to depict PD pathology. RESULTS: The signals of nigrosomes-1 were strong, droplet-like or oval in shape, and were found in 49 patients from the N-PD group (96.08%), on both sides of the SN (47 cases) and unilaterally (2 cases). In contrast, these signals were absent in all 54 cases from the PD group, and were undetected in 7 out of 11 cases in the UD group, 7 cases without the "drop" and 1 case with narrow strips of hyperintensity were clinically proven to PD, 2 cases with the typical hyperintensity were clinically proven to Parkinson's plus syndrome, 2 cases with slightly wider strip of hyperintensity were less sensitive to the drug levodopa. CONCLUSIONS: The absence of typical droplet-like or oval-shaped nigrosomes-1 signals in 3.0T MR SWI may prove useful in identifying PD and Parkinson's syndrome with high sensitivity and specificity.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Enfermedad de Parkinson/diagnóstico , Sustancia Negra/patología , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/patología , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador
7.
Transplant Proc ; 47(9): 2746-51, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26680086

RESUMEN

Heart transplantation has been widely accepted as a therapy for end-stage heart failure. Mitigation of ischemia-reperfusion injury by inhibiting the apoptotic process plays an important role in organ transplantation. Desiccation using high-pressure carbon monoxide (CO) is a new method of preserving donor hearts; however, its mechanism of antiapoptosis remains unclear. This study was intended to elucidate the efficacy and mechanism of preservation by desiccation for 18 hours using high-pressure CO on myocardial apoptosis. Rabbit heterotopic abdominal cardiac transplantation models were established. New Zealand rabbits were divided randomly into 3 groups: naive group (n = 16), HTK group (n = 16), and desiccation using high-pressure CO group (n = 16). The donor hearts of the naive group were transplanted immediately after being extracted. In the HTK group, the donor hearts were extracted and steeped in 4°C HTK cardioplegic solution for 18 hours and then transplanted; in the desiccation using high-pressure CO group, the donor hearts were extracted and exposed to a gas mixture (Po2 = 3200 hPa, Pco = 800 hPa) in the chamber before being preserved in a refrigerator at 4°C for 18 hours and then transplanted. Apoptotic cardiomyocytes were detected using TUNEL technique and histopathology was performed by hematoxylin-eosin staining. The expression of the ratio of Bcl-2/Bax and caspase-3 proteins was detected using the Western blot method. These findings suggest that compared with traditional HTK preservation, preservation by desiccation using high-pressure CO could alleviate rabbits' myocardial histopathology and apoptosis induced by ischemia-reperfusion injury through adjusting the ratio of Bcl-2/Bax protein expression, thus resulting in the reduction of expression of caspase-3.


Asunto(s)
Apoptosis , Monóxido de Carbono , Soluciones Cardiopléjicas , Desecación/métodos , Corazón , Preservación de Órganos/métodos , Presión , Animales , Caspasa 3/metabolismo , Criopreservación , Trasplante de Corazón , Etiquetado Corte-Fin in Situ , Conejos , Daño por Reperfusión/prevención & control
8.
Eur Rev Med Pharmacol Sci ; 19(18): 3480-5, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26439046

RESUMEN

OBJECTIVE: To explore the correlation between the features of a carotid plaque of patients suffering from carotid atherosclerosis and ischemic cerebrovascular disease by 64 slices computed tomography (CT). PATIENTS AND METHODS: One hundred patients with carotid atherosclerosis were divided into the ischemic event group (n=48) and non-ischemic event group (n=52). The features of the carotid plaque were detected by 64 slices CT. RESULTS: One hundred and thirteen plaques were found in the ischemic event group. The proportions of fatty, calcified, and mixed plaque were 35.4%, 30.1%, and 34.5%. There are 78 plaques found in the non-ischemic event group. The proportions of fatty, calcified, and mixed plaque were 21.8%, 51.3%, and 26.9%. The distribution difference between the three types of plaques was statistically significant (p<0.05). The proportions of mixed plaque composed mainly of fatty plaque were 64.1% and 23.8%. These two constituent ratios are significantly different from those of statistical processing (p<0.01). There are 10 cases of plaque ulceration out of the 100 cases, among which eight are from the ischemic event group and two cases from the other group. After statistical processing, the incidence rates of plaque ulceration from these two groups are significantly different (p<0.05). CONCLUSIONS: The 64 slices CT can accurately present the morphological features of the carotid plaque. It indicates that the fatty plaque, mixed plaque composed mainly of fatty plaque and ulcerative plaque can cause ischemic cerebrovascular events.


Asunto(s)
Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Trastornos Cerebrovasculares/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad
9.
Eur Rev Med Pharmacol Sci ; 19(11): 2001-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26125261

RESUMEN

OBJECTIVE: Discuss the effect of rhythmic auditory stimulation with visual stimuli on motor and balance function in patients with Parkinson's disease (PD). PATIENTS AND METHODS: One hundred and sixteen patients with PD participated in this study. The control group used a routine drug treatment for eight weeks. The comprehensive treatment group used conventional drug treatment with sound rhythm metronome released as the rhythmical auditory stimulation, in accordance with the ground fixed ribbon rhythmic visual stimulation walking training for eight weeks. After four and eight weeks, the two groups of subjects took the walking parameters test, and used the disease Parkinson score scale to assess the damaged degree of motor function of PD patients. The Berg Balance Scale was used to evaluate the balance function of the PD patients. A six minute walk test was used to evaluate the walking motor function of the patients. RESULTS: The comparison between the groups suggests that after treatment of rhythmic auditory stimulation with visual stimulation group, the step size increased, frequency decreased, pace increased, and PD score scale part II decreased. As well, the PD score scale part III reduced, the six minute walking distance increased, and the Berg Balance Scale score increased significantly. There were significant differences compared with the control group after the treatment (p < 0.01). Comparison of time points suggests that after rhythmic auditory stimulation with visual stimulation group trained for eight weeks, the step size increased, frequency decreased, pace increased, and PD score scale part II were reduced. As well the PD score scale part III reduced, six minute walking distance increased, Berg Balance Scale increased. There were significant differences compared with the parameters of training for four weeks (p < 0.01). CONCLUSIONS: Rhythmic auditory stimulation with visual stimulation can improve motor and balance function of patients with PD.


Asunto(s)
Estimulación Acústica , Enfermedad de Parkinson/rehabilitación , Periodicidad , Equilibrio Postural , Anciano , Benserazida/uso terapéutico , Benzotiazoles/uso terapéutico , Catecoles/uso terapéutico , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Femenino , Marcha , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Nitrilos/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Piribedil/uso terapéutico , Pramipexol , Caminata
10.
Eur Rev Med Pharmacol Sci ; 19(14): 2603-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26221889

RESUMEN

OBJECTIVE: This research aims to evaluate the effect of mecobalamin treatment on the recovery of patients with posterior communicating artery aneurysm inducing oculomotor nerve palsy after embolization. PATIENTS AND METHODS: A total of 56 patients with oculomotor nerve palsy (ONP) attributed to posterior communicating artery (PcomA), were admitted and treated in the Neurology Department of Hubei College of Medicine affiliated to Xiangyan Hospital from July 2007 to January 2013, and 55 of them were followed up as well. Among them 27 patients were given embolization treatment and 28 received embolization + mecobalamin treatment. The recovery condition of ONP were followed and compared one year after the treatment. RESULTS: All patients were followed up for more than a year. And 31 patients (56.4%) out of 55 achieved complete recovery, 19 (34.5%) attained partial recovery and 5 (9.1%) had no recovery from ONP. Whereas, 20 patients (71.4%) in the embolization + mecobalamin treatment group achieved complete recovery and 11 (40.7%) in the embolization treatment group achieved partial recovery, and the comparative difference was statistically significant (p < 0.05). CONCLUSIONS: Endovascular is highly efficacious treatment for ONP-inducing PcomA and can promote the recovery of oculomotor nerve palsy after embolism.


Asunto(s)
Embolización Terapéutica/métodos , Aneurisma Intracraneal/tratamiento farmacológico , Enfermedades del Nervio Oculomotor/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Recuperación de la Función/efectos de los fármacos , Vitamina B 12/análogos & derivados , Adulto , Anciano , Procedimientos Endovasculares/tendencias , Femenino , Hospitalización/tendencias , Humanos , Aneurisma Intracraneal/complicaciones , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Oculomotor/etiología , Complicaciones Posoperatorias/etiología , Recuperación de la Función/fisiología , Resultado del Tratamiento , Vitamina B 12/farmacología , Vitamina B 12/uso terapéutico
11.
Eur Rev Med Pharmacol Sci ; 19(14): 2608-13, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26221890

RESUMEN

OBJECTIVE: To evaluate the recurrent ischemic events and risk factors in patients with symptomatic intracranial artery stenosis. PATIENTS AND METHODS: Patients with acute cerebral infarction or transient ischemia attach (TIA) and intracranial arterial stenosis confirmed through CTA examination, were enrolled from the Department of Neurology. All cases were followed-up regularly and divided into recurrent group and non-recurrent group according to occurrence of cerebrovascular events. Major observation index: (1) the occurrence of endpoint; (2) new stroke in responsible artery; (3) drug therapy compliance was used. RESULTS: A total of 142 cases fulfilled the inclusion criteria, among them 121 cases (85.2%) completed the follow-up, and in 16 cases (13.2%) ischemic cerebrovascular stroke events occurred within one year, while among these vascular lesions recurred on the ipsilateral side in 12 cases (75%). Single factor analysis showed that difference between recurrent group and non-recurrent group on irregular use of statins (p = 0.017), diabetes mellitus (p = 0.017) and severe arterial stenosis (p = 0.030) were statistically significant. Logistic regression analysis showed that irregular use of statins (OR=3.719, p = 0.005), diabetes (OR=1.842. p = 029) and severe arterial stenosis (OR=1.503. p = 0.045) were correlated with the recurrence of symptomatic intracranial artery stenosis. CONCLUSIONS: Patients with symptomatic intracranial artery stenosis had a higher recurrence rate of stroke; whereas patients with irregular use of statins, diabetes and severe arterial stenosis had a higher recurrence risk of stroke.


Asunto(s)
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Arterias Cerebrales/patología , Anciano , Antihipertensivos/uso terapéutico , Constricción Patológica/diagnóstico , Constricción Patológica/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología
12.
Sci Rep ; 4: 3633, 2014 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-24407193

RESUMEN

We developed a new approach to test the single-photon emissions of semiconductor quantum dots (QDs) in the optical communication band. A diamond-anvil cell pressure device was used for blue-shifting the 1.3 µm emissions of InAs/GaAs QDs to 0.9 µm for detection by silicon avalanche photodiodes. The obtained g((2))(0) values from the second-order autocorrelation function measurements of several QD emissions at 6.58 GPa were less than 0.3, indicating that this approach provides a convenient and efficient method of characterizing 1.3 µm single-photon source based on semiconductor materials.

13.
Eur Rev Med Pharmacol Sci ; 18(24): 3908-15, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25555883

RESUMEN

OBJECTIVE: The purpose of this study was to examine whether the prevalence of Parkinson's disease (PD) continues to rise after 80 years of age. METHODS: This is a two-stage, multi-center, cross-sectional study using a stratified cluster sampling approach was employed. Subjects included veterans at ≥ 60 years of age living in veterans' communities for at least one month in 18 major cities across China. In the first step, possible PD was screened using a PD screening scale. Demographic and relevant information were collected. In the second step, PD diagnosis was established using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) diagnostic criteria. RESULTS: The study was conducted during the period from December 2009 to December 2012. The study included 277 veterans' communities. Among the approached 11,593 subjects, 9676 subjects, (9096 men, 580 women) responded. The response rate was 83.46%.The age was ≥ 80 years in 6722 (69.47%) subjects. A diagnosis of PD was established in 228 subjects (2.36%) in the entire sample. The rate of PD was 2.65% in those with an age of ≥ 80 years. The rate of PD increased with increasing age (0%, 1.84%, 2.60% and 3.68% in the subjects at < 70, 70-79, 80-89 and ≥ 90 years of age, respectively; χ2 = 10.891, p = 0.001 in chi-square test). The rate of PD was higher in men (2.44%) than in women (1.46%) on the surface. However, no significant difference was detected (p = 0.241). CONCLUSIONS: The prevalence of PD continues to increase beyond the age of 80 years. The prevalence of PD in Chinese veterans is not lower than that in other countries and regions.


Asunto(s)
Enfermedad de Parkinson/epidemiología , Veteranos/estadística & datos numéricos , Factores de Edad , Anciano , Pueblo Asiatico , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reino Unido
14.
Eur Rev Med Pharmacol Sci ; 17(8): 1051-9, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23661518

RESUMEN

BACKGROUND: TGF-ß (Transforming Growth Factor-ß) mediates its biological effects through members of activin receptor-like kinase (ALK) family and TGF-ß/Smad3 signaling link inflammation to pulmonary fibrosis. AIM: The aim of this study was to evaluate the role of SB431542 as a specific inhibitor of Activin receptor-Like Kinase 5 (ALK5) in pneumonic injury. MATERIALS AND METHODS: Anesthetized and endo-tracheally intubated C57BL/6 mice were randomized to three groups: the control group with intra-tracheal instillation of 1.5 mg/kg normal saline (NS); LPS stimulation group with intra-tracheal instillation of 3 mg/kg LPS (lipopolysaccharide); and LPS+SB431542 group with intra-peritoneal (i.p.) injection of 4.2 mg/kg SB431542 1 h before intra-tracheal instillation of 3 mg/kg LPS. The lung tissue was obtained 6 h after injury, and the degree of pulmonary injury was evaluated by pathologic scoring. The lung wet/dry weight ratio was measured. TNF-α, IL-1ß, and MMP-9 (matrix metallopeptidase-9) mRNA expression levels were assayed by real time PCR (polymerase chain reaction). The content of MMP-9 total protein was measured by Western blotting. The content of active MMP-9 was detected by gelatin zymography. Location of MMP-9 in mouse lung tissue was monitored by immunohistochemistry. RESULTS: The results showed that (1) pathologic changes including interstitial pulmonary edema, neutrophil infiltration, alveolar edema and hemorrhage were observed 6 h after LPS instillation. The lung wet/dry weight rate and pathologic scores confirmed that SB431542 administration aggravated LPS injury to the mouse lung; (2) the amount of TNF-α and IL-1ß mRNA expression in LPS groups was significantly higher than that in the control group, and the highest in LPS+SB431542 group; (3) the amount of MMP-9 mRNA and MMP-9 protein expression and active MMP-9 in the lung tissue of LPS groups was significantly higher than that in the control group 6 h after injury, and the highest in LPS+SB431542 group; and (4) MMP-9 expression was mainly observed in the airway epithelial cells, vascular smooth muscle cells and cytoplasm of inflammatory cells as shown by immunohistochemistry, and brownish yellow uniformed stained areas were also seen in the exudate from part of the alveoli. CONCLUSIONS: These results indicate that blocking the activity of TGF-ß/Smad pathway by specific inhibitor SB431542 of ALK5 promoted the releaser of large amounts of TNF-α, IL-1ß and other pro-inflammatory cytokines from the lung tissue of mice sustaining acute lung injury (ALI). At the same time, the amount and activity of MMP-9 expression in the lung were increased, and MMP-9 expression was mainly located in the airway epithelial cells, vascular smooth muscle cells and inflammatory cells, causing increased permeability of the pulmonary blood vessels, degradation of the extracellular matrix and destruction of the normal lung tissue structures, which directly or indirectly promotes the progression of pulmonary inflammatory responses and aggravates ALI.


Asunto(s)
Lipopolisacáridos/toxicidad , Lesión Pulmonar/etiología , Metaloproteinasa 9 de la Matriz/genética , Proteínas Serina-Treonina Quinasas/fisiología , Receptores de Factores de Crecimiento Transformadores beta/fisiología , Animales , Benzamidas/uso terapéutico , Dioxoles/uso terapéutico , Interleucina-1beta/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética
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