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1.
Acta Physiologica Sinica ; (6): 1-9, 2021.
Article in Chinese | WPRIM | ID: wpr-878229

ABSTRACT

Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.


Subject(s)
Animals , Astrocytes , Hippocampus , Interneurons , Mice , Neurons , bcl-2-Associated X Protein/genetics
2.
Article in Chinese | WPRIM | ID: wpr-880101

ABSTRACT

OBJECTIVE@#To investigate the effect of 2-methoxyestradiol (2-ME2) to lymphoma Raji cells and its mechanism.@*METHODS@#Different concentrations of 2-ME2 were used to treat lymphoma Raji cells. CCK8 method was used to detect the effect of 2-ME2 to proliferation of Raji cells. Flow cytometry FITC/PI double labeling method was used to detect early apoptosis of the cells. Western blotting was used to detect the effect of 2-ME2 to the expression of BCL-2, Bax, Caspase-3 and C-myc proteins in Raji cells.@*RESULTS@#2-ME2 significantly inhibited the proliferation of Raji cells. The inhibition rate increased with the increasing of drug concentration, and increased significantly with the prolongation of drug treatment time (r=0.9215). Flow cytometry FITC/PI double staining showed that the apoptotic rate of 2.5 μmol/L 2-ME2 treatment group was (33.79±1.63) %, while the apoptosis rate of the 48 h group was (51.90±2.72) %, and that of the control group was (7.08±0.36) %. After treated with 2.5 μmol/L 2-ME2 for 12 h, the expression of Bax protein was up-regulated, BCL-2 protein was down-regulated, caspase-3 protein expression was up-regulated, and C-myc protein expression was down-regulated, all of them showed a time-dependent relationship.@*CONCLUSION@#2-ME2 shows obvious inhibitory effect on lymphoma Raji cells in a dose- and time-dependent manner. Its mechanism of treatment on lymphoma Raji cells may be related to up-regulation of Bax/BCL-2 ratio and activation of Caspase-3 to induce apoptosis in cancer cells. Down-regulation of C-myc protein expression also participates in the apoptotic process.


Subject(s)
2-Methoxyestradiol , Apoptosis , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation , Humans , Lymphoma , Proto-Oncogene Proteins c-bcl-2/metabolism , Up-Regulation , bcl-2-Associated X Protein
3.
Article in Chinese | WPRIM | ID: wpr-879185

ABSTRACT

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.


Subject(s)
Animals , Apoptosis , Mice , Myocardial Ischemia/drug therapy , Myocardium , Myocytes, Cardiac , Plant Extracts/pharmacology , Rhus , bcl-2-Associated X Protein
4.
Int. j. morphol ; 38(2): 427-434, abr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056458

ABSTRACT

Granulosa cells (GCs) are essential components of follicles and play a role in regulating follicle development. The aim of this study was to investigate certain cellular components involved in the proliferation, differentiation and functional characteristics of granulosa cells in the success of fertilization of human oocytes during invitro fertilization (IVF) via immunohistochemical techniques. In this study, 30 patients who were diagnosed as primary or secondary infertility, polycystic ovary syndrome in the IVF center of Memorial Hospital, Department of Obstetrics and Gynecology were included. The amount of Anti Müllerian Hormone (AMH) in blood and granulosa cell diameter and cell core diameter were measured in 20 cells collected from each patient. In addition, degeneration scoring and BAX, ADAMTS-1, IL-10 expressions in granulosa cells were evaluated (p <0.01). It was thought that apoptosis induced by human GCs might be an indicator of egg quality. Moderate expression of ADAMTS-1 was thought to be related to failure of ovulation, deterioration of oocyte quality and decreased fertilization rate. This decrease in AMH levels may be associated with defects in granulosa cells. Therefore, significantly lower AMH secretion and increase in IL10 expression levels in healthy people can be explained by the increase of granulocyte cells.


Las células de la granulosa (GC) son componentes esenciales de los folículos y tienen un papel en la regulación del desarrollo de éste. El objetivo del estudio fue investigar ciertos componentes celulares involucrados en la proliferación, diferenciación y características funcionales de las células de la granulosa en el éxito de la fertilización de los ovocitos humanos durante la fertilización in vitro (FIV) a través de técnicas inmunohistoquímicas. En este estudio, se incluyeron 30 pacientes diagnosticados con infertilidad primaria o secundaria, síndrome de ovario poliquístico en el centro de FIV del Departamento de Obstetricia y Ginecología del Hospital Memorial. La cantidad de Hormona Anti Mülleriana (AMH) en la sangre, el diámetro de las células de la granulosa y el diámetro del núcleo celular se midieron en 20 células obtenidas de cada paciente. Además, se evaluó la puntuación de degeneración y las expresiones BAX, ADAMTS-1, IL-10 en células de granulosa (p <0,01). Se estimó que la apoptosis inducida por los GC humanos podría ser un indicador de la calidad del huevo. Se estimó que la expresión moderada de ADAMTS-1 estaba relacionada con el fracaso de la ovulación, el deterioro de la calidad de los ovocitos y la disminución de la tasa de fertilización. La disminución en los niveles de AMH puede estar asociada con defectos en las células de la granulosa. Por lo tanto, el aumento de las células de granulocitos puede explicar la disminución significativa de la secreción de AMH y el aumento de los niveles de expresión de IL10 en personas sanas.


Subject(s)
Humans , Female , Fertilization in Vitro/methods , Interleukin-10/metabolism , bcl-2-Associated X Protein/metabolism , ADAMTS1 Protein/metabolism , Granulosa Cells/metabolism , Immunohistochemistry
5.
Int. j. morphol ; 37(2): 584-591, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1002262

ABSTRACT

Following the success of the highly active antiretroviral therapy, the potential of multidrug combination regimen for the management of cancer is intensely researched. The anticancer effects of curcumin on some human cell lines have been documented. Lopinavir is a FDA approved protease inhibitor with known apoptotic activities. Dysregulated apoptosis is important for the initiation of cancer while angiogenesis is required for cancer growth and development, this study therefore investigated the effects of the combination of lopinavir and curcumin on cell viability, apoptosis and the mRNA expression levels of key apoptotic and angiogenic genes; BAX, BCL2 and VEGF165b in two human cervical cell lines; human squamous cell carcinoma cells - uterine cervix (HCS-2) and transformed normal human cervical cells (NCE16IIA). The two human cervical cell lines were treated with physiologically relevant concentrations of the agents for 120 h following which BAX, BCL2 and VEGF165b mRNA expression were determined by Real Time qPCR. The Acridine Orange staining for the morphological evaluation of apoptotic cells was also performed. The combination of lopinavir and curcumin up-regulated pro-apoptotic BAX and antiangiogenic VEGF165b but down-regulated the mRNA levels of anti-apoptotic BCL2 mRNA in the human squamous cell carcinoma (HCS-2) cells only. The fold changes were statistically significant. Micrographs from Acridine Orange staining showed characteristic evidence of apoptosis in the human squamous cell carcinoma (HCS-2) cells only. The findings reported here suggest that the combination of curcumin and the FDA approved drug-lopinavir modulate the apoptotic and angiogenic pathway towards the inhibition of cervical cancer.


Tras el éxito de la terapia antirretroviral altamente activa, se investiga intensamente el potencial del régimen de combinación de múltiples fármacos para el tratamiento del cáncer. Se han documentado los efectos anticancerígenos de la curcumina en algunas líneas celulares humanas. Lopinavir es un inhibidor de proteasa aprobado por la FDA con actividades apoptóticas conocidas. La apoptosis disrregulada es importante para el inicio del cáncer, mientras que la angiogénesis es necesaria para el crecimiento y desarrollo del cáncer. Por lo tanto, este estudio investigó los efectos de la combinación de lopinavir y curcumina sobre la viabilidad celular, la apoptosis y los niveles de expresión del ARNm de genes apoptóticos y angiogénicos clave: BAX, BCL2 y VEGF165b en dos líneas celulares cervicales humanas; células de carcinoma de células escamosas humanas: cérvix uterino (HCS-2) y células cervicales humanas transformadas (NCE16IIA). Las dos líneas celulares cervicales humanas se trataron con concentraciones fisiológicamente relevantes de los agentes durante 120 horas, después de lo cual la expresión de ARNm de BAX, BCL2 y VEGF165b se determinó mediante qPCR en tiempo real. También se realizó la tinción con naranja de acridina para la evaluación morfológica de células apoptóticas. La combinación de lopinavir y curcumina reguló incrementando BAX proapoptósicos y VEGF165b antiangiogénicos, pero reguló a la baja los niveles de ARNm del BCL2 antiapoptótico en células de carcinoma de células escamosas humanas (HCS-2) únicamente. Los cambios en el pliegue fueron estadísticamente significativos. Las micrografías de la tinción con naranja de acridina mostraron evidencia característica de apoptosis solo en las células del carcinoma de células escamosas humanas (HCS-2). Los hallazgos reportados aquí sugieren que la combinación de curcumina y el fármaco aprobado por la FDA lopinavir modulan la vía apoptótica y angiogénica hacia la inhibición del cáncer cervical.


Subject(s)
Humans , Female , Carcinoma, Squamous Cell/drug therapy , Uterine Cervical Neoplasms/drug therapy , Curcumin/pharmacology , Lopinavir/pharmacology , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Apoptosis/drug effects , Cell Line, Tumor/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/genetics , bcl-2-Associated X Protein/drug effects , bcl-2-Associated X Protein/genetics , Real-Time Polymerase Chain Reaction
6.
Journal of Experimental Hematology ; (6): 1749-1753, 2019.
Article in Chinese | WPRIM | ID: wpr-781402

ABSTRACT

OBJECTIVE@#To investigate the effect of BAX gene deletion on the sensitivity of BCR-ABL-induced B-ALL cells of mice to imatinib and the related mechanism.@*METHODS@#The target gene-knock out (BAX) mice were used as bone marrow cell donors; the wild type bone marrow cells(B6BM) and BAX bone marrow cells(B6BM-BAX) of mice were transfected by using reverse transcription virus, then the BCR-ABL transfected B6BM cells and B6BM-BAX cells were treated with imatinib at different concentration (0,0.5, 1.0 and 2.0 μmol/L) for 48 hours. The number of viable cells was detected by trypan blue, the flow cytometry was used to detect the cell apoptosis, the Western blot was used to detect the changes of BAX, Caspase expression.@*RESULTS@#In BCR-ABL transfected bone marrow cells treated with imatinib, the numbers of viable cells of BAX deletion group was significantly higher than that of wild type groups with statristcal difference(P<0.05), and effect- and dose-dependency(r=-0.9533 for BAX deletion group, and r=-0.9812 for wild type group). The flow cytometry showed that the cell apoptosis in BAX deletion group signifincantly decreased, compared with wild type group(P<0.05). The Western blot showed that the expression of apoptotic protein Caspase 3 in BAX deletion group was significantly higher than that in wild type group(P<0.05).@*CONCLUSION@#BAX deletion can reduce the sensitivity of BCR-ABL-induced B-ALL cells to imatinib.


Subject(s)
Animals , Apoptosis , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl , Gene Deletion , Imatinib Mesylate , Mice , Piperazines , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Genetics , bcl-2-Associated X Protein
7.
Article in English | WPRIM | ID: wpr-776636

ABSTRACT

OBJECTIVE@#To investigate the effects of ethanol extract of Patrinia scabiosaefolia (EEPS) on chemo-resistance of colorectal cancer cells (CRC) and explore the possible molecular mechanisms.@*METHODS@#5-fluorouracil (5-FU)-resistant human colorectal carcinoma cell line (HCT-8/5-FU) and its parental cells HCT-8 were treated with EEPS (0, 0.25, 0.50, 1 or 2 mg/mL), or 5-FU (0, 100, 200, 400, 800 or 1600 μmol/L). The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the cell viability. Cell density was observed by phase-contrast microscope, cell counting and colony formation assay were used to determine the cell proliferation of HCT-8/5-FU cells treated with 0, 0.5, 1 or 2 mg/mL EEPS. Cell apoptosis was determined by Hoechst staining. Western-blot was performed to detect the phosphorylation of AKT as well as the protein expression level of B-cell CLL/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax).@*RESULTS@#Compared with HCT-8 cells, MTT assay results indicated that HCT-8/5-FU cells were resistant to 5-FU treatment (P0.05). Moreover, compared with untreated HCT-8/5-FU cells, 1 and 2 mg/mL of EEPS treatment significantly reduced cell density, cell number, inhibited cell survival (P<0.05), and induced apoptosis in HCT-8/5-FU cells. Furthermore, 1 and 2 mg/mL of EEPS significantly decreased the phosphorylation level of p-AKT and Bcl-2 protein expression, and increased the expression of Bax protein (P<0.05).@*CONCLUSION@#EEPS is a promising therapeutic agent that may overcome chemo-resistance in cancer cells, likely through suppression of the AKT pathway and promotion of cancer cell apoptosis.


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Cell Survival , Colorectal Neoplasms , Drug Therapy , Pathology , Drug Resistance, Neoplasm , Fluorouracil , Pharmacology , Therapeutic Uses , Humans , Patrinia , Chemistry , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Signal Transduction , Tumor Stem Cell Assay , bcl-2-Associated X Protein , Metabolism
8.
Article in English | WPRIM | ID: wpr-776602

ABSTRACT

OBJECTIVE@#To determine the effects of hawthorn extract on serum lipid levels, pathological changes in aortic atherosclerosis plaque, inflammatory factors, and apoptosis-related protein and mRNA expression in apolipoprotein E gene knockout (ApoE) mice.@*METHODS@#Thirty-six ApoE mice were fed with a high-fat diet starting at the age of 8 weeks. Mice were randomly divided into 3 groups by a random number table including model group, hawthorn extract group, and simvastatin group, 12 mice in each group. Twelve 8-week-old C57BL/6 mice were fed a basic diet and served as control. The mice in the control and model groups were administered 0.2 mL saline daily, the mice in the hawthorn extract and simvastatin groups were administered with 50 mg/kg hawthorn extract or 5 mg/kg simvastatin daily for 16 weeks. After 16 weeks, plasma lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by an enzymatic assay. Aortic atherosclerotic lesions were observed by light microscopy, scanning and transmission electron microscopy, respectively. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), adiponectin (APN), and hypersensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of Bax and Bcl-2 in the aorta were assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively.@*RESULTS@#Compared to the control group, the plasma levels of TC, TG and LDL-C were significantly increased and HDL-C were significantly decreased in the model group (P<0.01). Compared to the model group, treatment with hawthorn extract significantly decreased the plasma levels of TC, TG, and LDL-C and increased the plasma level of HDL-C in ApoE mice (P<0.01). The levels of MCP-1, IL-1ß, and hs-CRP in the model group were significantly increased and APN was significantly decreased compared with the control group (P<0.01). Compared to the model group, treatment with hawthorn extract decreased the levels of MCP-1, IL-1ß, and hs-CRP and increased the APN level (P<0.01). Compared to the control group, the protein and mRNA expression of Bax in the model group were significantly increased and the expression of Bcl-2 was significantly decreased (P<0.01). Hawthorn extract also reduced the protein and mRNA expression of Bax and increased the Bcl-2 expression in the aorta (P<0.01).@*CONCLUSION@#Hawthorn extract has anti-atherosclerosis and stabilizing unstable plaque effects. The mechanism may be related to the inflflammation and apoptosis signaling pathways.


Subject(s)
Animals , Aorta , Pathology , Apoptosis , Atherosclerosis , Blood , Drug Therapy , Crataegus , Chemistry , Inflammation , Blood , Drug Therapy , Inflammation Mediators , Metabolism , Lipids , Blood , Male , Mice, Inbred C57BL , Plant Extracts , Pharmacology , Therapeutic Uses , RNA, Messenger , Genetics , Metabolism , bcl-2-Associated X Protein , Metabolism
9.
Article in Chinese | WPRIM | ID: wpr-776558

ABSTRACT

OBJECTIVE@#To observe the effects of Shenmai injection(SM) on p38MAPK and the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion (I/R) in rats and to investigate the protective mechanism of SM.@*METHODS@#Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery (SMA) for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: control group, intestinal ischemia/reperfusion group(I/R group), Shenmai injection treated group (SM+I/R group). Lung wet/dry weight ratio(W/D), the contents of phosphatidylcholine (PC) and total phospholipid(TPL) which are the major ingredients of pulmonary surfactant were measured, as well as the expression levels of p38MAPK, Bcl-2 and Bax proteins in lung tissue were examined by using immunohistochemical method.@*RESULTS@#Compared with control group, lung W/D was significantly increased, the contents of PC and TPL were significantly decreased, the protein expression levels of p38MAPK, Bcl-2 and Bax were significantly increased in I/R group (all P<0.01). But Bax protein expression was much greater than Bcl-2 protein expression, the ratio of Bcl-2 to Bax were significantly decreased in I/R group than that in control group (P<0.01). Compared with I/R group, lung W/D was significantly decreased, while the contents of PC and TPL were significantly increased, the p38MAPK and Bax protein expression levels were significantly decreased in SM+I/R group (all P<0.01); both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SM+I/R group than those in I/R group (P<0.01). The correlation analysis indicated that the expression level of p38MAPK protein in lung tissue was negatively correlated with the contents of PC and the ratio of Bcl-2 to Bax (r is -0.787 and -0.731, all P<0.01).@*CONCLUSION@#SM can protect the lung injury induced by intestinal I/R injury, which may be mediated by inhibiting the activation of p38MAPK, improving the ratio of Bcl-2 to Bax to inhibit lung apoptosis.


Subject(s)
Animals , Apoptosis , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Lung Injury , Drug Therapy , Genetics , Proto-Oncogene Proteins c-bcl-2 , Random Allocation , Rats , Rats, Sprague-Dawley , Reperfusion Injury , bcl-2-Associated X Protein , p38 Mitogen-Activated Protein Kinases , Metabolism
10.
Article in Chinese | WPRIM | ID: wpr-775895

ABSTRACT

OBJECTIVE@#To explore the mechanism of acupuncture plus medication on treatment of Alzheimer's disease (AD).@*METHODS@#Sixty adult SD rats were randomly divided into a normal group, a sham operation group, a model group, an electroacupuncture (EA) group, a gastrodin group and an EA+gastrodin group, 10 rats in each one. The rat model of AD was established by intraperitoneal injection of D-galactose and bilateral hippocampal injection of Aβ1-40. Two weeks after modeling, the rats in the EA group and EA+gastrodin group were treated with EA at "Baihui" (GV 20) "Dazhui" (GV 14) and bilateral "Zusanli" (ST 36), 30 min per treatment, once a day for consecutive 4 weeks. The rats in the gastrodin group and EA+gastrodin group were treated with intraperitoneal injection of gastrodin, once a day for consecutive 4 weeks. The rats in the normal group, model group and sham operation group were not treated. The morphology of hippocampal neurons was observed by using HE staining. The expression of Bcl-2 and Bax in the hippocampal CA1 area was detected by using immunohistochemical method. The expression of Bcl-2 and Bax protein in hippocampus was detected by using Western blot.@*RESULTS@#The HE staining results showed the arrangement of neurons in the hippocampal CA1 area was regular in the normal group and the sham operation group, and the cytoplasm and nucleus were clearly visible. The neurons in the model group were severely damaged; the cell arrangement was not close, and the cell morphology was incomplete. Compared with the model group, the cell morphology of each intervention group was significantly improved. The immunohistochemistry results showed that, compared with the normal group and the sham operation group, the expression of Bcl-2 in the hippocampal CA1 region in the model group was decreased (<0.05), but the expression of Bax was enhanced (<0.05); compared with the model group, the expression of Bcl-2 was increased (all <0.05) and the expression of Bax was decreased (all <0.05) in all intervention group; compared with the EA group or the gastrodin group, the expression of Bcl-2 was enhanced (<0.05) and the expression of Bax was decreased (<0.05) in the EA+gastrodin group. The result of Western blot method was consistent with that of immunohistochemistry method.@*CONCLUSION@#EA and gastrodin could significantly inhibit the expression of Bax and up-regulate the expression of Bcl-2, and the combination of EA and gastrodin has the most significant effect. This indicates that EA combined with gastrodin has synergistic effect on inhibiting the apoptosis of neurons in hippocampus in AD rats, which may be one of the mechanisms of EA plus medication on AD lesions.


Subject(s)
Alzheimer Disease , Animals , Electroacupuncture , Hippocampus , Proto-Oncogene Proteins c-bcl-2 , Rats , Rats, Sprague-Dawley , bcl-2-Associated X Protein
11.
Article in Chinese | WPRIM | ID: wpr-813082

ABSTRACT

To explore the effect of connexin 43 (Cx43) silence on the apoptosis in mouse chondrocyte under mechanical stress.
 Methods: Mouse chondrocyte ATDC5 cells were divided into a control group, a mechanical stress group, a Cx43 siRNA transfection group, a scramble siRNA transfection group, a mechanical stress+scramble group, and a mechanical stress+siCx43 group. Flexcell FX-5000 system was used to produce mechanical stress on ATDC5 cells cultured in vitro. The mRNA and protein level of Cx43 was detected by quantitative RT-PCR (RT-qPCR) and Western blot. The cell activity and cell apoptosis was detected by cell counting kit-8 (CCK-8) method and flow cytometry, respectively. Caspase-3 activity was detected by colorimetric assay. The protein expression of Bcl-2, Bax, p-JNK and JNK was detected by Western blot.
 Results: Mechanical stress upregulated the mRNA and protein expression of Cx43 (both P<0.05). Transfection of Cx43 siRNA significantly decreased Cx43 mRNA and protein level (both P<0.05). After stimulation with mechanical stress, chondrocyte viability was significantly decreased, whereas cell apoptosis and caspase-3 activity were increased (both P<0.05). Mechanical stress obviously upregulated Bax protein level, and downregulated Bcl-2 protein expression and Bcl-2/Bax (both P<0.05). Cx43 siRNA transfection significantly increased cell viability, inhibited cell apoptosis and caspase-3 activity (both P<0.05). Cx43 siRNA also inhibited Bax expression, and increased the Bcl-2 protein expression and Bcl-2/Bax (both P<0.05). Furthermore, Cx43 siRNA significantly suppressed the p-JNK expression induced by mechanical stress (P<0.05).
 Conclusion: Cx43 silence inhibits mechanical stress-induced apoptosis in chondrocyte, which might be mediated by JNK signaling pathway.


Subject(s)
Animals , Apoptosis , Chondrocytes , Connexin 43 , Mice , Proto-Oncogene Proteins c-bcl-2 , Stress, Mechanical , bcl-2-Associated X Protein
12.
Article in Chinese | WPRIM | ID: wpr-773691

ABSTRACT

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.


Subject(s)
Animals , Apoptosis , Chemical and Drug Induced Liver Injury , Drugs, Chinese Herbal , Toxicity , Female , Glycosides , Toxicity , Heme Oxygenase-1 , Metabolism , Lipid Peroxidation , Liver , Male , Membrane Proteins , Metabolism , Mice , NF-E2-Related Factor 2 , Metabolism , Oxidative Stress , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Random Allocation , Tablets , Tripterygium , Toxicity , bcl-2-Associated X Protein , Metabolism
13.
Article in Chinese | WPRIM | ID: wpr-773272

ABSTRACT

To investigate the inhibitory effects and mechanism of Cistanche tubulosa ethanol extract( CTEE) against oxygen-glucose deprivation/reperfusion( OGD/R)-induced PC12 cells neuronal injury. In this study,OGD/R-induced PC12 cells were used to explore the neuroprotective effects of CTEE( 12. 5,25,50 mg·L-1) by detecting cell viability with MTT assay,apoptosis with AO/EB and Hoechst 33258,mitochondrial membrane potential changes with JC-1 staining,mitochondrial oxidative stress with MitoSOX staining,as well as the apoptosis-related protein expression( PARP,cleaved PARP,caspase-3,cleaved caspase-3,Bax,Bcl-2) with Western blot. RESULTS:: showed that CTEE effectively protected OGD/R-induced neuronal injury and increased the survival rate of PC12 cells.AO/EB and Hoechst 33258 staining showed that CTEE could effectively inhibit apoptosis. Moreover,JC-1 and MitoSOX staining results showed that CTEE decreased mitochondrial stress and mitochondrial membrane potential imbalance in PC12 cells in a concentration-dependent manner. Meanwhile,CTEE could obviously suppress the activation of key proteins in mitochondrial apoptosis pathway such as caspase-3 and PARP,and significantly inhibit the rise of Bax and down-regulation of Bcl-2. In conclusion,CTEE has obvious protective effects on OGD/R-induced PC12 cells neuronal injury,potentially via inhibiting mitochondrial oxidative stress and apoptosis-related signaling pathway.


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cistanche , Chemistry , Ethanol , Glucose , Neuroprotective Agents , Pharmacology , Oxidative Stress , Oxygen , PC12 Cells , Plant Extracts , Pharmacology , Poly (ADP-Ribose) Polymerase-1 , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats , bcl-2-Associated X Protein , Metabolism
14.
Article in Chinese | WPRIM | ID: wpr-773253

ABSTRACT

In this paper,the effects of active fractions of Ferula ferulaeoides on the growth and apoptosis of human gastric cancer cell MGC-803 transplantation tumor were systematically studied. The subcutaneous ectopic transplantation tumor model was established in human gastric cancer MGC-803 nude mice by cell suspension implantation method. The anti-tumor rate and organ index were used to evaluate the anti-tumor effect of the active fractions of F. ferulaeoides on the tumor-bearing nude mice. HE staining,TUNEL staining,RT-PCR,Western-blot and ELISA were used for pathological examination,apoptosis observation,and detection of apoptosis-related genes,proteins and cytokines expression. The results showed that as compared with the model group,the low,medium and high doses of the active fraction of F. ferulaeoides had inhibitory effects on xenografts in nude mice,respectively,in a dose-dependent manner; the apoptotic ratio was increased with the increase of drug concentration. As compared with the model group,F. ferulaeoides could down-regulate the expression of survivin mRNA in nude mice,and the protein expression levels of Bax,Bcl-2,caspase-3 and caspase-9 in tumor tissues of nude mice could be increased to different degrees in F. ferulaeoides groups. The contents of IL-10 and TGF-β1 in plasma of nude mice were decreased in high dose group of F. ferulaeoides active fractions. The results indicated that F. ferulaeoides can significantly inhibit the growth of human gastric cancer MGC-803 subcutaneously transplanted tumor,and its mechanism may be related with down-regulating the expression of survivin mRNA,and up-regulating the expression of apoptosis-related proteins Bax,caspase-3 and caspase-9.


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cell Line, Tumor , Cytokines , Metabolism , Ferula , Chemistry , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Plant Extracts , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Stomach Neoplasms , Drug Therapy , bcl-2-Associated X Protein , Metabolism
15.
Chinese Medical Journal ; (24): 948-956, 2019.
Article in English | WPRIM | ID: wpr-772171

ABSTRACT

BACKGROUND@#Cervical cancer has the fourth highest incidence and mortality rate of all cancers in women worldwide; it seriously harms their physical and mental health. The aim of this study was to observe the roles and preliminary mechanism of Taurine (Tau)-induced apoptosis in cervical cancer cells.@*METHODS@#Cells from the human cervical cancer cell line SiHa were transfected with the recombinant plasmid pEGFP-N1-MST1 (mammalian sterile 20-like kinase 1); then, the cell proliferation activity was analyzed by the MTT assay, cell apoptosis by flow cytometry, and the related protein levels by Western blotting.@*RESULTS@#Tau inhibited the proliferation of SiHa cells and induced apoptosis in these cells (the apoptotic rate was 21.95% in the Tau 160 mmol/L group and 30% in the Tau 320 mmol/L group), upregulated the expression of the MST1 (control, 0.53; Tau 40-320 mmol/L groups, 0.84-1.45) and Bax (control, 0.45; Tau 40-320 mmol/L groups, 0.64-1.51) proteins (P < 0.01), and downregulated the expression of Bcl-2 (control, 1.28, Tau 40-320 mmol/L groups, 0.93-0.47) (P < 0.01). The overexpression of MST1 promoted the apoptosis of SiHa cells, enhanced the apoptosis-inductive effects of Tau (P < 0.01), upregulated the expression of the proapoptotic proteins p73, p53, PUMA (p53 upregulated modulator of apoptosis), and caspase-3, and promoted the phosphorylation of YAP (Yes-associated protein).@*CONCLUSIONS@#Tau inhibited the proliferation and induced the apoptosis of cervical cancer SiHa cells. The MST1 protein plays an important role in the Tau-induced apoptosis of cervical cancer cells.


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Female , Hepatocyte Growth Factor , Metabolism , Humans , Proto-Oncogene Proteins , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Taurine , Pharmacology , Uterine Cervical Neoplasms , Metabolism , bcl-2-Associated X Protein , Metabolism
16.
Article in English | WPRIM | ID: wpr-719643

ABSTRACT

The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated IC50 value of 3 µM after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G1 phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/CHOP apoptotic pathway, and mitochondrial Ca2+ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER-and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.


Subject(s)
Apoptosis , bcl-2-Associated X Protein , Caspase 9 , Cell Death , Cell Line , Colon , Colonic Neoplasms , DNA Fragmentation , Endoplasmic Reticulum , Extracellular Vesicles , Humans , Inhibitory Concentration 50 , Lymphoma, B-Cell , Mitochondria , Mitochondrial Membranes , Protein Kinases
17.
Acta cir. bras ; 33(10): 896-903, Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-973463

ABSTRACT

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.


Subject(s)
Animals , Male , Female , Rabbits , Blast Injuries/physiopathology , Apoptosis/physiology , Acute Lung Injury/physiopathology , Pulmonary Alveoli/pathology , Blast Injuries/pathology , Blast Injuries/blood , Random Allocation , Proto-Oncogene Proteins c-bcl-2/blood , Disease Models, Animal , bcl-2-Associated X Protein/blood , Caspase 3/blood , Acute Lung Injury/pathology , Acute Lung Injury/blood
18.
Acta cir. bras ; 33(10): 868-878, Oct. 2018. graf
Article in English | LILACS | ID: biblio-973468

ABSTRACT

Abstract Purpose: To investigate the protective effects of Polygonatum sibiricum polysaccharide (PSP) on acute heart failure (AHF) in rats. Methods: Sixty rats were randomly divided into control, model, and low-, middle- and high-dose PSP groups, 12 rats in each group. The low-, medium- and high-dose PSP groups were intragastrically administrated with 100, 200 and 400 mg/kg PSP for 5 days, respectively. On the sixth day, the AHF model was established by intraperitoneal injection of adriamycin. After 24h, the cardiac function, serum biochemical indexes, myocardial ATPase and succinate dehydrogenase levels and apoptosis related protein expressions were determined. Results: Compared with model group, in high-dose PSP group the heart rate, left ventricular systolic pressure, ±dp/dtmax, serum superoxide dismutase level, myocardial Na+-K+-ATPase, Ca2+-Mg2+-ATPase and succinate dehydrogenase levels and myocardial Bcl-2 and Caspase-3 protein expression levels were significantly increased (P<0.05), the left ventricular end diastolic pressure, serum cTnI, CK-MB, TNF-α, IL-6, malondialdehyde and nitric oxide levels and myocardial Bax and cleaved Caspase-3 protein expression levels were significantly decreased (P<0.05). Conclusions: Polysaccharide can prevent the acute heart failure induced by adriamycin. The mechanism may be related to its anti-oxidative stress, anti-inflammation and inhibition of cardiac myocyte apoptosis.


Subject(s)
Animals , Male , Rats , Polysaccharides/therapeutic use , Doxorubicin/pharmacology , Polygonatum/chemistry , Heart Failure/prevention & control , Acute Disease , Rats, Sprague-Dawley , Apoptosis/drug effects , Oxidative Stress/drug effects , Disease Models, Animal , bcl-2-Associated X Protein/drug effects , bcl-2-Associated X Protein/metabolism
19.
Acta cir. bras ; 33(10): 889-895, Oct. 2018. tab
Article in English | LILACS | ID: biblio-973469

ABSTRACT

Abstract Purpose: To investigate the role of the exogenous supply of adenosine triphosphate (ATP) in the expression of Bax and Bcl2L1 genes in intestinal ischemia and reperfusion (IR) in rats. Methods: The study was designed as a randomized controlled trial with a blinded assessment of the outcome. Eighteen adult male Wistar-EPM1 rats were housed under controlled temperature and light conditions (22-23°C, 12 h light/dark cycle). The animals were randomly divided into 3 groups: 1. Sham group (SG): no clamping of the superior mesenteric artery; 2. Ischemia and reperfusion group (IRG): 3. Ischemia and reperfusion plus ATP (IRG + ATP). ATP was injected in the femoral vein before and after ischemia. Afterwards, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. Results: ATP promoted the upregulation of Bcl2L1 gene expression, whereas it did not have significant effects on Bax gene expression. In addition, the relation of Bax/Bcl2L1 gene expression in the IRG group was 1.39, whereas it was 0.43 in the IRG + ATP group. Bcl2L1 plays a crucial role in protecting against intestinal apoptosis after ischemia and reperfusion. Increased Bcl2L1 expression can inhibit apoptosis while decreased Bcl2L1 expression can trigger apoptosis. Conclusion: Adenosine triphosphate was associated with antiapoptotic effects on the rat intestine ischemia and reperfusion by upregulating of Bcl2L1 gene expression.


Subject(s)
Animals , Male , Rats , Adenosine Triphosphate/pharmacology , Apoptosis/drug effects , Genes, bcl-2 , bcl-2-Associated X Protein/genetics , Ischemia/genetics , Reperfusion Injury/etiology , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/drug therapy , Random Allocation , Gene Expression , Up-Regulation , Rats, Wistar , Proto-Oncogene Proteins c-bcl-2/metabolism , Disease Models, Animal , bcl-2-Associated X Protein/drug effects , bcl-2-Associated X Protein/metabolism , bcl-X Protein , Intestines , Ischemia/complications
20.
Rev. bras. cir. cardiovasc ; 33(4): 384-390, July-Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-958430

ABSTRACT

Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.


Subject(s)
Animals , Flavonoids/pharmacology , Protective Agents/pharmacology , Myocardial Infarction/prevention & control , Reference Values , Superoxide Dismutase/analysis , Thromboxane A2/blood , Enzyme-Linked Immunosorbent Assay , Random Allocation , Reproducibility of Results , Chromatography, High Pressure Liquid , Epoprostenol/blood , Treatment Outcome , Rats, Sprague-Dawley , Genes, bcl-2 , Creatine Kinase, MB Form/blood , bcl-2-Associated X Protein/analysis , Hemodynamics/drug effects , L-Lactate Dehydrogenase/blood , Malondialdehyde/analysis
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