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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(1): 63-68, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32314725

RESUMO

Objective To explore the value of double labeling of P16/ki67, E6/E7 mRNA of human papillomavirus (HPV) and combined detection in shunt diagnosis of low-grade squamous intraepithelial lesions (LSIL) by thin-layer cervical cytology (TCT). Methods The study enrolled 239 patients who underwent colposcopy and biopsy within 4 weeks after primary TCT diagnosis. The remaining cytological samples were double-labeled with P16/ki67 immunocytochemical staining and the HPV E6/E7 mRNA was detected by Panther automatic HPV E6/E7 mRNA detection system. Using SPSS22.0 software, the positive rates of P16/ki67 double-labeling, HPV E6/E7 mRNA and combined detection were analyzed in different cervical lesions, and the positive rates in the same cervical lesions were compared horizontally to evaluate the efficiency of double labeling of P16/ki67, HPV E6/E7 and combined detection in the diagnosis of high-grade squamous intraepithelial lesions (HSIL) and above lesions. Results The diagnostic results of HE staining for the 239 cases of LSIL were 71 cases of chronic cervicitis (29.71%), 143 cases of LSIL (59.83%), 22 cases of HSIL (9.20%) and 3 cases of cervical cancer (1.26%). There were 46 cases of P16+ki67+ lesions (19.25%), 41 cases of ki67+P16- lesions (17.15%), 33 cases of ki67-P16+ lesions (13.81%) and 119 cases of P16-ki67- lesions (49.79%). The positive rates of P16/ki67 double-labeling, HPV E6/E7 mRNA and combined detection increased with the severity of cervical lesions. The positive rate of combined detection was the highest in the HSIL lesions, which was higher than that of P16/ki67 double-labeling and HPV E6/E7 mRNA detection. The sensitivity of combined detection was higher than that of P16/ki67 double-labeling and HPV E6/E7 mRNA detection. The Youden index of joint detection was 0.7850. Conclusion The combined detection of P16/ki67 double labeling, HPV E6/E7 mRNA and HPV E6/E7 mRNA had a certain clinical value in the management of cell LSIL shunt diagnosis. The combined detection significantly improved the sensitivity and Youden index of HSIL and above lesions, while maintaining a high specificity and coincidence rate.

2.
Int J Mol Med ; 45(6): 1697-1710, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32236616

RESUMO

Substantial evidence indicates that circular RNAs (circRNAs) play vital roles in several diseases, especially in cancer development. However, the functions of circRNAs in breast cancer metastasis remain to be investigated. This study aimed to identify the key circRNAs involved in epithelial mesenchymal transition (EMT) of breast cancer and evaluated their molecular function and roles in pathways that may be associated with tumor metastasis. An EMT model was constructed by treating breast cancer cells MCF­7 and MDA­MB­231 with transforming growth factor­ß1. High­throughput RNA sequencing was used to identify the differentially expressed circRNAs in EMT and blank groups of two cells, and reverse transcription­quantitative PCR was used to validate the expression of circSCYL2 in human breast cancer tissues and cells. The effects of circSCYL2 on breast cancer cells were explored by transfecting with plasmids and the biological roles were assessed using transwell assays. EMT groups of breast cancer cells exhibited the characteristics of mesenchymal cells. Furthermore, the present study found that 7 circRNAs were significantly upregulated in both the MCF­7 EMT and MDA­MB­231 EMT groups, while 16 circRNAs were significantly downregulated. The current study identified that circSCYL2 was downregulated in breast cancer tissues and cell lines, and that circSCYL2 overexpression inhibited cell migration and invasion. This study provides expression profiles of circRNAs in EMT groups of breast cancer cells. circSCYL2, which is downregulated in breast cancer tissues and cells, may play an important role in breast cancer EMT progression.

3.
FEBS Open Bio ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32175684

RESUMO

Breast cancer is the second leading cause of cancer-related deaths in women. The long noncoding RNA (lncRNA) LINC00115 has been reported to be involved in the poor outcome of patients with breast cancer, but the biological function and underlying mechanism remain unclear. Here, we report that LINC00115 expression is increased in triple-negative breast cancer (TNBC) tissue compared with matched normal tissue, and LINC00115 knockdown suppresses breast cancer cell migration and invasion. Furthermore, we show that LINC00115 directly targets miR-7 and inhibits its expression. LINC00115 also reduces the expression of KLF4, which is a direct target of miR-7 and is involved in breast cancer metastasis. Together, our findings suggest that LINC00115 promotes breast cancer metastasis through modulating the expression of miR-7 and KLF4.

4.
BMC Infect Dis ; 19(1): 812, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533652

RESUMO

BACKGROUND: Invasive group B Streptococcus (GBS) disease in Chinese infants has gradually gained attention in recent years, but the molecular epidemiology of the pathogen is still not well known. METHODS: This multicenter study retrospectively investigated distribution of capsular serotypes, sequence types (STs), and hypervirulent GBS adhesin gene (hvgA) in clinical GBS isolates that caused invasive disease in infants aged < 3 months of age in southern mainland China between January 2013 and June 2016. Genes for antibiotic resistance to tetracycline, erythromycin, and clindamycin were also examined. RESULTS: From a total of 93 GBS isolates taken from 34 early-onset disease (EOD, 0-6 days after birth) and 59 late-onset disease (LOD, 7-89 days after birth) cases, four serotypes were identified: serotypes III (79.6%), Ib (12.9%), Ia (4.3%), and V (3.2%). Serotype III accounted for 73.5% of EOD and 83.1% of LOD and was responsible for 75.5% of cases involving meningitis. Fifteen STs were found, with the majority being ST17 (61.3%), ST12 (7.5%), ST19 (7.5%), and others (23.7%). 96.8% of STs belonged to only five clonal complexes (CCs): CC17 (64.5%), CC10 (12.9%), CC19 (9.7%), CC23 (6.5%), and CC1 (3.2%). The hvgA gene was detected in 66.7% of GBS isolates and 95% of CC17 isolates, all of which were serotype III except one serotype Ib/CC17 isolate. A large proportion of GBS isolates were found to be resistant to tetracycline (93.5%), clindamycin (65.5%), and erythromycin (60.2%). Genes of tetO (74.7%) and tetM (46.0%) were found in tetracycline resistant isolates, linB (24.6%) in clindamycin resistant isolates, and ermB (87.5%) and mefA (3.6%) in erythromycin resistant isolates. CONCLUSION: Our results reveal higher prevalence of serotype III, ST17, CC17, hvgA expressing, and antibiotic resistant GBS isolates than previously reported in southern mainland China. This study provides guidance for appropriate measures of prevention and control to be taken in the future.


Assuntos
Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Adesinas Bacterianas/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Tipagem de Sequências Multilocus , Prevalência , Estudos Retrospectivos , Sorogrupo , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/patologia , Streptococcus agalactiae/genética
5.
Biosci Rep ; 39(7)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31262968

RESUMO

Long non-coding RNAs (lncRNAs) have been widely reported that involved in human cancers, including papillary thyroid carcinoma (PTC). The present study aims to investigate the biological role of LINC00982 in PTC. The mRNA expression of LINC00982 in human PTC tissues was detected using qPCR. Moreover, Kaplan-Meier method was performed to analyze the internal relevance between LINC00982 expression and overall survival (OS) rate of patients with PTC. In addition, gain- and loss-of-functions assays were performed to detect the effects of LINC00982 on the cell proliferation and migration in PTC cells. Furthermore, western blot assay was used to measure the alteration expression levels of apoptosis relative proteins and the relative protein involved phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Finally, a xenograft model was used to analyze the antitumor role of LINC00982 in vivo Here, we found that LINC00982 was decreased in human PTC tissues. Patients with decreased LINC00982 expression levels had a reduced OS (P=0.0019) compared with those with high LINC00982 expression levels. Overexpression of LINC00982 suppressed the proliferation and migration of BHT101 and B-CPAP cells and promoted cell apoptosis. Knockdown of LINC00982 promoted the proliferation and migration of BHT101 and B-CPAP cells and induced cell apoptosis. Moreover, in vivo assay showed that overexpression of LINC00982 could suppress the growth of PTC. Finally, LINC00982 could regulate the activity of PI3K/AKT signaling pathway in vitro and in vivo Taken together, our findings demonstrated that overexpression of LINC00982 could suppress cell proliferation and induce cell apoptosis by regulating PI3K/AKT signaling pathway in PTC.

6.
BMC Plant Biol ; 19(1): 282, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248374

RESUMO

BACKGROUND: Heavy metal toxicity has become a major threat to sustainable crop production worldwide. Thus, considerable interest has been placed on deciphering the mechanisms that allow plants to combat heavy metal stress. Strategies to deal with heavy metals are largely focused on detoxification, transport and/or sequestration. The P1B subfamily of the Heavy Metal-transporting P-type ATPases (HMAs) was shown to play a crucial role in the uptake and translocation of heavy metals in plants. Here, we report the locus-specific expression changes in the rice HMA genes together with several low-copy cellular genes and transposable elements upon the heavy metal treatment and monitored the transgenerational inheritance of the altered expression states. We reveal that plants cope with heavy metal stress by making heritable changes in gene expression and further determined gene-specific responses to heavy metal stress. RESULTS: We found most HMA genes were upregulated in response to heavy metal stress, and furthermore found evidence of transgenerational memory via changes in gene regulation even after the removal of heavy metals. To explore whether DNA methylation was also altered in response to the heavy metal stress, we selected a Tos17 retrotransposon for bisulfite sequencing and studied its methylation state across three generations. We found the DNA methylation state of Tos17 was altered in response to the heavy metal stress and showed transgenerational inheritance. CONCLUSIONS: Collectively, the present study elucidates heritable changes in gene expression and DNA methylation in rice upon exposure to heavy metal stress and discusses implications of this knowledge in breeding for heavy metal tolerant crops.


Assuntos
Adenosina Trifosfatases/genética , Epigênese Genética/genética , Expressão Gênica/genética , Metais Pesados/efeitos adversos , Oryza/genética , Proteínas de Plantas/genética , Poluentes do Solo/efeitos adversos , Adenosina Trifosfatases/metabolismo , Oryza/enzimologia , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico
7.
J Biomed Nanotechnol ; 15(5): 1043-1051, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30890234

RESUMO

The immune checkpoint molecule B7-H4 is highly expressed in various types of cancer, but little is known about its role in the development of cervical lesions associated with human papilloma virus (HPV). This study aimed to investigate the role of B7-H4 in cervical lesion progression and the relationship between B7-H4 and HPV infection. This was a retrospective study of tissue samples from 30 patients with cervical cancer, 28 with cervical intraepithelial neoplasia (CIN), and 75 with cervical inflammatory lesions. Serum-soluble B7-H4 (sB7-H4) was assessed by ELISA. Tissue B7-H4 expression was measured by RT-PCR and immunochemistry. Expression of B7-H4 in dendritic cells was assessed by flow cytometry. sB7H4 increased gradually from the patients with cervical inflammation to patients with cervical cancer and decreased after treatment. sB7-H4 had a diagnostic value in cervical intraepithelial neoplasia (CIN (area under the curve (AUC) = 0.8929) and cervical cancer (AUC = 0.9545). B7-H4 expression in inflammatory cervical tissue and peripheral blood dendritic cells (DCs) increased gradually from inflammation to cancer (P < 0.001). sB7-H4 was positively associated with B7-H4 expression in cervical tissue and DCs and with the frequency of CD4+CD25+Foxp3+ regulatory T cells (P < 0.001). The level of sB7-H4, and tissue and DC B7-H4 expression were associated with HPV infection (P < 0.001). These data strongly support the use of sB7-H4 for monitoring the progression of cervical cancer associated with HPV, and for evaluating the immune status of the patients.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Feminino , Humanos , Inflamação , Prognóstico , Estudos Retrospectivos , Doenças do Colo do Útero , Inibidor 1 da Ativação de Células T com Domínio V-Set
8.
Onco Targets Ther ; 12: 647-656, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30705593

RESUMO

Background: Although increasing evidence has demonstrated important roles for long non-coding RNAs (lncRNAs) in cancer development, their functions in oral squamous cell carcinoma (OSCC) growth remain largely unknown. Therefore, we aimed to investigate the role of LINC00662 in OSCC. Methods: The expression of LINC00662 in 61 OSCC tissues and four OSCC cell lines were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and EdU staining methods. Migration and invasion abilities were analyzed using transwell and wound healing assay. Cell cycle distribution and apoptosis rate were evaluated by flow cytometry. Western blot method was performed to detect protein expression. Results: We found that the expression of LINC00662 was significantly increased in OSCC tissues, and a higher expression of LINC00662 was detected in larger tumor size, higher stage tumors and with lymph node metastasis. Moreover, overexpression of LINC00662 induced OSCC cell proliferation, increased migration and invasion abilities, and suppressed cell apoptosis. Knockdown of LINC00662 decreased the proliferation, migration, and invasion abilities of OSCC cell, and induced apoptosis. Furthermore, LINC00662 regulated the Wnt/ß-catenin pathway. Conclusion: Our data indicate that LINC00662 may represent a novel indicator of OSCC and may be a potential therapeutic target for diagnosis and therapy.

9.
BMC Infect Dis ; 18(1): 14, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29310577

RESUMO

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants in both developed and developing countries. To our knowledge, only a few studies have been reported the clinical features, treatment and outcomes of the GBS disease in China. The severity of neonatal GBS disease in China remains unclear. Population-based surveillance in China is therefore required. METHODS: We retrospectively collected data of <3 months old infants with culture-positive GBS in sterile samples from three large urban tertiary hospitals in South China from Jan 2011 to Dec 2014. The GBS isolates and their antibiotic susceptibility were routinely identified in clinical laboratories in participating hospitals. Serotyping and multi-locus sequence typing (MLST) were also conducted for further analysis of the neonatal GBS disease. RESULTS: Total 70 cases of culture-confirmed invasive GBS infection were identified from 127,206 live births born in studying hospitals, giving an overall incidence of 0.55 per 1000 live births (95% confidence interval [CI] 0.44-0.69). They consisted of 49 with early-onset disease (EOD, 0.39 per 1000 live births (95% CI 0.29-0.51)) and 21 with late-onset disease (LOD, 0.17 per 1000 live births (95% CI 0.11-0.25)). The incidence of EOD increased significantly over the studying period. Five infants (4 EOD and 1 LOD) died before discharge giving a mortality rate of 7.1% and five infants (7.1%, 2 EOD and 3 LOD) had neurological sequelae. Within 68 GBS isolates from GBS cases who born in the studying hospitals or elsewhere, serotype III accounted for 77.9%, followed by Ib (14.7%), V (4.4%), and Ia (2.9%). MLST analysis revealed the presence of 13 different sequence types among the 68 GBS isolates and ST-17 was the most frequent sequence type (63.2%). All isolates were susceptible to penicillin, ceftriaxone, vancomycin and linezolid, while 57.4% and 51.5% were resistant to erythromycin and clindamycin, respectively. CONCLUSIONS: This study gains the insight into the spectrum of GBS infection in south China which will facilitate the development of the guidance for reasonable antibiotics usage and will provide evidence for the implementation of potential GBS vaccines in the future.


Assuntos
Infecções Estreptocócicas/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Farmacorresistência Bacteriana , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/microbiologia , Masculino , Tipagem de Sequências Multilocus , Estudos Retrospectivos , Sorogrupo , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus/classificação , Streptococcus/efeitos dos fármacos , Streptococcus/isolamento & purificação
10.
Oncol Rep ; 34(6): 3097-103, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26398855

RESUMO

HSPC238 is a recently identified tumor suppressor and demonstrates ubiquitin ligase E3 enzyme activity. HSPC238 was found to be significantly downregulated in human hepatocellular carcinoma (HCC) in vivo and to inhibit the proliferation and invasion of hepatoma cells in vitro; however, the underlying molecular mechanism is largely unknown. In the present study, we screened for and identified proteins that physically interact with HSPC238. A bait vector for yeast two-hybrid was constructed with human HSPC238 gene cDNA. Yeast two-hybrid screening was performed using a human fetal liver cDNA library. Multiple reporter gene assays, DNA sequencing and BLAST comparison analysis were performed on positive clones. Protein interaction of screened candidates with HSPC238 was further validated by confocal microscopy, co-immunoprecipitation and pull-down assays. Yeast two-hybrid screening demonstrated 124 positive clones. Multiple reporter gene assays with LacZ, HIS and ADE2 selective media identified 12 genes. Further co-localization, co-immunoprecipitation and pull-down assays demonstrated that HMOX1, RPS27A, ubiquitinB and MT2A interacted with HSPC238. These four proteins are involved in tumor development and progression, and are associated with the ubiquitin-proteasome pathway. Our results suggest that HSPC238 may play a tumor suppressor role and interact with these proteins via the ubiquitin-proteasome pathway. The identification and validation of proteins interacting with HSP238 may lead to the discovery of novel mechanisms through which HSPC238 suppresses tumorigenesis in human hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/metabolismo , Ubiquitina-Proteína Ligases/genética , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Biblioteca Gênica , Vetores Genéticos , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/genética , Ligação Proteica , Técnicas do Sistema de Duplo-Híbrido , Ubiquitina-Proteína Ligases/metabolismo
12.
Clin Immunol ; 136(1): 30-41, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20346734

RESUMO

Previous studies demonstrate that both membrane B7-H4 and B7-H4-Ig fusion protein could inhibit T-cell responses. In the present study, we explored the potential effect of B7-H4-Ig on liver injury in a hepatitis mouse model induced by concanavalin A (ConA). A B7-H4-Ig construct was introduced into animals by the hydrodynamic gene delivery approach. It was found that ectopic expression of B7-H4-Ig could inhibit ConA-induced elevation of serum levels of ALT and AST, suppress liver necrosis and even mortality of mice. Furthermore, we observed that pretreatment of B7-H4-Ig dramatically decreased serum levels and the expression of mRNA for IL-2, IFN-gamma and IL-4, but increased IL-10 in ConA-treated mice. Our results suggest that B7-H4-Ig may protect animals from liver injury induced by ConA, which could be associated with reduced serum levels for IL-2, IFN-gamma and IL-4 as well as enhanced IL-10 production.


Assuntos
Antígeno B7-1/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Concanavalina A/farmacologia , Terapia Genética/métodos , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/genética , Proteínas Recombinantes de Fusão/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Antígeno B7-1/sangue , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Técnicas de Transferência de Genes , Humanos , Fragmentos Fc das Imunoglobulinas/sangue , Interferon gama/sangue , Interferon gama/genética , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-2/sangue , Interleucina-2/genética , Interleucina-4/sangue , Interleucina-4/genética , Leucócitos Mononucleares/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Necrose/induzido quimicamente , Necrose/patologia , Proteínas Recombinantes de Fusão/sangue , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Análise de Sobrevida , Inibidor 1 da Ativação de Células T com Domínio V-Set
13.
Transpl Immunol ; 21(3): 143-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19361556

RESUMO

B7-H4, a recently discovered member of B7 family, can negatively regulate T cell responses. However, it is not clear whether B7-H4 negatively function in cell transplantation. In this study we investigated the immunosuppressive effect of B7-H4 on beta-cell transplantation. An insulinoma cell line, NIT-1, transfected with B7-H4 (B7-H4-NIT) was established, and transplanted to diabetic C57BL/6 mice by intraperitoneal injection. Proliferation assay of splenocytes in vitro showed that B7-H4-NIT suppressed alloreactive T cell activation. The proportion of IFN-gamma-producing cells in recipient spleen was significantly reduced and the number of Treg cells was upregulated in B7-H4-NIT group compared to the control, EGFP-NIT. The expression of mRNA coding IFN-gamma was lower but that of IL-4 was higher in B7-H4-NIT transplanted recipients than in the control animals. The results of ELISA also revealed the same trends. Diabetic mice reached normalglycemic quickly and gained weight after transplantation of B7-H4-NIT. More importantly, the survival time for recipients transplanted with B7-H4-NIT cells was significantly longer than that with EGFP-NIT cells. These results indicate that B7-H4 transfection prolongs beta-cell graft survival.


Assuntos
Antígeno B7-1/imunologia , Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Tipo 1/cirurgia , Sobrevivência de Enxerto/imunologia , Imunossupressão/métodos , Células Secretoras de Insulina/transplante , Animais , Antígeno B7-1/genética , Linhagem Celular Tumoral , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Tipo 1/imunologia , Sobrevivência de Enxerto/genética , Proteínas de Fluorescência Verde/imunologia , Proteínas de Fluorescência Verde/metabolismo , Células Secretoras de Insulina/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Interleucina-4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/imunologia , Transfecção , Inibidor 1 da Ativação de Células T com Domínio V-Set
14.
Int Immunopharmacol ; 8(6): 792-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18442782

RESUMO

The present study was designed to investigate whether administration of CoPPIX, an HO-1 inducer, could significantly inhibit TNF-alpha and Hmgb1 expression and thus attenuate the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Acute lung injury was induced successfully by intratracheal administration of LPS (0.5 mg/kg) in male BALB/c mice. CoPPIX or ZnPPIX (an HO-1 inhibitor) was administered to mice 24 h prior to LPS exposure. It was found that CoPPIX (5, 10 mg/kg, i.p.) caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and EBA leakage at 24 h after LPS challenge. Furthermore, the histopathologic findings indicated that alveolitis with leukocyte infiltration in the alveolar space was less severe in the CoPPIX-treated mice than in the mice treated with LPS alone. In addition, CoPPIX was also believed to have down-regulated the expression of LPS-induced proinflammatory cytokines, including early proinflammatory cytokine TNF-a, and late proinflammatory cytokine Hmgb1. In contrast, no obvious difference was observed between the ZnPPIX group and the LPS group. These findings demonstrate the significant protection of CoPPIX against LPS-induced ALI, and the effect mechanism of CoPPIX was associated with decreasing the expression of TNF-a and Hmgb1.


Assuntos
Proteína HMGB1/metabolismo , Heme Oxigenase-1/metabolismo , Protoporfirinas/farmacologia , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Relação Dose-Resposta a Droga , Lipopolissacarídeos , Pulmão/enzimologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Protoporfirinas/administração & dosagem , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/prevenção & controle , Regulação para Cima
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