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1.
Pharmacol Res ; 171: 105574, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34419228

RESUMO

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Flavonoides/farmacologia , Neoplasias Pulmonares/metabolismo , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Flavonoides/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Metabolômica , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Esfingolipídeos/metabolismo
2.
Sci Rep ; 10(1): 7039, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341437

RESUMO

Nectar is the most common floral reward for flower-visiting flies, bees, bats and birds. Many flowers hide nectar in the floral tube and preclude sensing of nectar by flower-visitors from a distance. Even in those flowers that offer easily accessible nectar, the nectaries are mostly inconspicuous to the human eye and the amount of nectar is sparse. It is widely accepted that many flowers display nectar guides in order to direct flower-visitors towards the nectar. Using false colour photography, covering ultraviolet, blue and green ranges of wavelength, revealed a yet unknown conspicuousness of nectar, nectaries and false nectaries for bees due to concordant reflection in the ultraviolet range of wavelength. Nectars, many nectaries and false nectaries have glossy surfaces and reflect all incident light including UV-light. In most cases, this is not particularly conspicuous to the human eye, but highly visible for UV-sensitive insects, due to the fact that the glossy areas are often positioned in UV-absorbing central flower parts and thus produce a strong UV-signal. The optical contrast produced by the glossiness of small smooth areas in close proximity to nectar holders represents a widespread yet overlooked floral cue that nectarivorous flower-visitors might use to locate the floral nectar.


Assuntos
Flores , Mimetismo Molecular , Néctar de Plantas/química , Polinização , Animais , Abelhas/fisiologia , Aves/fisiologia , Cor , Insetos/fisiologia
3.
Mol Ther Nucleic Acids ; 16: 675-685, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31121479

RESUMO

Dysregulated microRNAs (miRNAs) play crucial roles in the regulation of cancer stem cells (CSCs), and CSCs are closely associated with tumor initiation, metastasis, and recurrence. Here we found that miR-150-5p was significantly downregulated in CSCs of non-small-cell lung cancer (NSCLC) and its expression level was negatively correlated with disease progression and poor survival in patients with NSCLC. Inhibition of miR-150-5p increased the CSC population and sphere formation of NSCLC cells in vitro and stimulated NSCLC cell tumorigenicity and metastatic colonization in vivo. In contrast, miR-150-5p overexpression potently inhibited sphere-formed NSCLC cell tumor formation, metastatic colonization, and recurrence in xenograft models. Furthermore, we identified that miR-150-5p significantly inhibited wingless (Wnt)-ß-catenin signaling by simultaneously targeting glycogen synthase kinase 3 beta interacting protein (GSKIP) and ß-catenin in NSCLC cells. miR-150-5p also targeted high mobility group AT-hook 2 (HMGA2), another regulator of CSCs, and Wnt-ß-catenin signaling. The restoration of HMGA2 and ß-catenin blocked miR-150-5p overexpression-induced inhibition of CSC traits in NSCLC cells. These findings suggest that miR-150-5p functions as a CSC suppressor and that overexpression of miR-150-5p may be a novel strategy to inhibit CSC-induced metastasis and recurrence in NSCLC.

4.
RSC Adv ; 9(37): 21134-21138, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35521328

RESUMO

The molecular mechanism of cancer cell death caused by silver nanoparticles (AgNPs) of different sizes is investigated. Compared with the larger nanoparticles, 13 nm AgNPs significantly inhibit the migration and invasiveness of lung adenocarcinoma A549 cells, induce elevated reactive oxygen species and lead to NF-κB directed cellular apoptosis.

5.
J Pharmacol Exp Ther ; 347(3): 615-25, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24049062

RESUMO

Benzoxaboroles are a novel class of drug-like compounds that have been rich sources of novel inhibitors for various enzymes and of new drugs. While examining benzoxaborole activity in phenotypic screens, our attention was attracted by the (aminomethylphenoxy)benzoxaborole family, which potently inhibited Toll-like receptor-stimulated cytokine secretion from leukocytes. After considering their structure-activity relationships and the central role of kinases in leukocyte biology, we performed a kinome-wide screen to investigate the members of the (aminomethylphenoxy)benzoxaborole family. This technique identified Rho-activated kinase (ROCK) as a target. We showed competitive behavior, with respect to ATP, and then determined the ROCK2-drug cocrystal structure. The drug occupies the ATP site in which the oxaborole moiety provides hydrogen bond donors and acceptors to the hinge, and the aminomethyl group interacts with the magnesium/ATP-interacting aspartic acid common to protein kinases. The series exhibits excellent selectivity against most of the kinome, with greater than 15-fold selectivity against the next best member of the AGC protein kinase subfamily. Medicinal chemistry efforts with structure-based design resulted in a compound with a Ki of 170 nM. Cellular studies revealed strong enzyme inhibition rank correlation with suppression of intracellular phosphorylation of a ROCK substrate. The biochemical potencies of these compounds also translated to functional activity, causing smooth muscle relaxation in rat aorta and guinea pig trachea. The series exhibited oral availability and one member reduced rat blood pressure, consistent with ROCK's role in smooth muscle contraction. Thus, the benzoxaborole moiety represents a novel hinge-binding kinase scaffold that may have potential for therapeutic use.


Assuntos
Compostos de Boro/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Animais , Aorta Torácica/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Citocinas/sangue , Humanos , Células Jurkat , Modelos Moleculares , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Fosforilação , Inibidores de Proteínas Quinases/química , Proteína Fosfatase 1/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Traqueia/efeitos dos fármacos , Quinases Associadas a rho/genética
6.
Zhonghua Yi Xue Za Zhi ; 93(16): 1258-60, 2013 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-23902620

RESUMO

OBJECTIVE: To explore the expression of Tau protein in breast invasive ductal carcinomas and examine the correlation between its expression and clinicopathological characteristics of breast cancer. METHODS: The clinicopathological data of 150 breast cancer patients at Third Municipal Hospital from October 2007 to June 2011 were collected and analyzed. Immunohistochemical method was used to detect the expressions of estrogen receptor (ER), progesterone receptor (PR), HER-2 and Tau protein. RESULTS: No correlations existed between the expression of Tau protein and age, tumor size or node metastasis of breast cancer patients (χ(2) = 0.02, P = 0.88; χ(2) = 0.55, P = 0.46; χ(2) = 1.02, P = 0.31). The expressions of Tau in ER positive patients were significantly higher than ER negative patients. And this trend extended to PR positive and HER-2 negative patients (χ(2) = 15.77, P = 0.00; χ(2) = 5.03, P = 0.03; χ(2) = 8.00, P = 0.01). The expression of Tau protein in Luminal A subtype was significantly higher than in Luminal B subtype, HER-2 over-expression subtype and basal like subtype (χ(2) = 7.26, P = 0.01). CONCLUSIONS: Over-expressed in breast cancer, Tau protein is associated with ER, PR and HER-2. However, the relation between Tau protein and prognosis of breast cancer requires further researches.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Proteínas tau/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
7.
Bioorg Med Chem Lett ; 23(6): 1680-3, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23411072

RESUMO

A series of novel 6-(aminomethylphenoxy)benzoxaborole analogs was synthesized for the investigation of the structure-activity relationship of the inhibition of TNF-alpha, IL-1beta, and IL-6, from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compounds 9d and 9e showed potent activity against all three cytokines with IC50 values between 33 and 83nM. Chloro substituted analog 9e (AN3485) is considered to be a promising lead for novel anti-inflammatory agent with a favorable pharmacokinetic profile.


Assuntos
Anti-Inflamatórios/química , Benzoxazóis/química , Compostos de Boro/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacocinética , Compostos de Boro/metabolismo , Compostos de Boro/farmacocinética , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Meia-Vida , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Cinética , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Camundongos , Ligação Proteica , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
8.
Clin Lung Cancer ; 12(3): 192-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21663863

RESUMO

OBJECTIVE: This pilot study was designed to evaluate the clinical value of assaying tumor supplied group of factor/tumor specific growth factor (TSGF) in solitary pulmonary nodule (SPN). PATIENTS AND METHODS: The study was conducted from March 2007 to September 2010 and included 33 patients with SPN and 28 healthy volunteers. TSGF was assayed in preoperative serum, intraoperative pleural lavage fluid (IPLF), and postoperative serum. RESULTS: At operation, 20 patients were diagnosed with malignancy and 13 patients were diagnosed with nonmalignancy and placed in group A and group B, respectively. In group A, pathologic staging demonstrated 8 patients (group A1) with stage T1N0M0, 7 patients (group A2) with stage T1N1M0 and 53 patients (group A) with stage T1N2M0 disease. In group B, 8 patients were diagnosed with tuberculoma (group B1) and 5 patients were diagnosed with inflammatory pseudotumor (group B2). Before operation, levels of TSGF in peripheral blood were significantly higher in group A compared with group B and the control group (98.8 ± 29.9 vs. 62.1 ± 24.9 and 50.1 ± 17.9, Student-Newman-Keuls test; P < .05). The percentage of patients with positive serum TSGF results was significantly higher in group A than in group B or the control group (90.0% vs. 30.8% and 17.9%, χ(2) test; P < .05). With respect to the diagnostic value of serum TSGF in malignant SPN, we found sensitivity to be 90%, specificity to be 69.2%, positive forecast rate to be 74.5%, negative forecast rate to be 87.4%, and accurate diagnosed rate to be 79.5%. The TSGF level in IPLF in group A was significantly higher than that in group B (132.2 ± 51.9 vs. 84.6 ± 12.6, Student t test, P < .05). Additionally, TSGF in group A2 and group A3 was significantly higher compared with group A1 (162.2 ± 52.3 and 176.4 ± 17.8 vs. 100.2 ± 35.8, Student-Newman-Keuls test; P < .05). Postoperative serum TSGF in the patients diagnosed with lung cancer decreased significantly after operation. TSGF returned to a normal threshold level (71 U/mL) in the sixth month postoperatively. In addition, there was no appreciable change in the patients in group B. CONCLUSION: Serum TSGF is conducive to discriminating between benign and malignant features of SPN. Additionally, investigation of IPLF TSGF can potentially offer a new approach to predict the existence of lymph node metastases.


Assuntos
Biomarcadores Tumorais/sangue , Nódulo Pulmonar Solitário/diagnóstico , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pleura/química , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/cirurgia
9.
Mol Diagn Ther ; 15(1): 31-40, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21469768

RESUMO

OBJECTIVE: The purpose of the study was to evaluate clinical presentation of breast cancer anti-estrogen resistance protein 1 (BCAR1, also known as p130cas) expression in pulmonary diseases, and to assess its potential as a molecular marker for diagnosis and prognosis. METHODS: Between March 2008 and August 2010, we enrolled a total of 80 patients (group A) with non-small-cell lung cancer (NSCLC), 48 patients (group B) with pulmonary tuberculosis (including 27 cases of tuberculoma and 21 cases of cavitary pulmonary tuberculosis), and 32 patients (group C) with other benign pulmonary mass (hamartoma in 15 cases, inflammatory pseudotumor in 10 cases, fibroid tumor in 7 cases). Additionally, 160 healthy age- and sex-matched volunteers were recruited as healthy controls. Tissue BCAR1 expression was investigated by using tissue microarray and immunohistochemistry. BCAR1 and tumor markers (carcinoma embryonic antigen [CEA] and the cancer antigens CA19-9 and CA125) in serum were assayed by using ELISA and immunoradiometrics, respectively. RESULTS: BCAR1 expression was detected (either in the nucleus, the cytoplasm, or both) in tumor cells in 79 of the 80 NSCLC cases in group A, and in fibroblasts in 41 of the 48 pulmonary tuberculosis cases in group B. However, it was not detected in the normal adjacent tissue in 70 of the 80 cases in group A and in 47 of the 48 cases in group B. In group C, BCAR1 expression was negative in all 32 cases. Additionally, we investigated adjacent tissue with acute or chronic inflammation in 20 cases from group C, and found no expression of BCAR1. Serum BCAR1 levels were significantly higher in patients with NSCLC than in the control group, increased gradually with the progression of tumor staging, and decreased after removal of the tumors. The levels were significantly lower in bronchioloalveolar carcinoma than in other subtypes of carcinoma (Mann-Whitney U test, Z = -5.089; p < 0.001). Serum BCAR1 levels were significantly higher in patients with pulmonary tuberculosis than in the control group, were positively and significantly correlated with the diameter of the tuberculosis lesion (Spearman's rho, correlation coefficient 0.753; p < 0.001), and decreased after removal of the tuberculosis lesions. The levels were significantly higher in patients with cavitary pulmonary tuberculosis than in those with tuberculoma (517.6 ± 326.5 vs 282.2 ± 137.6; Student's t-test, t = -3.387; p = 0.001). In group C, there was no appreciable difference in serum BCAR1 levels compared with the matched controls (222.8 ± 111.0 vs 201.6 ± 35.7; Dunnett's T3 test, p = 0.993). The discrimination power of combining BCAR1 and tumor markers in NSCLC versus benign lung diseases was higher than that of sole use of BCAR1 as a marker (maximal sum of sensitivity and specificity: 1.538 vs 1.237). CONCLUSION: We conclude that a combined assay of serum BCAR1 and traditional tumor markers is potentially applicable for distinguishing NSCLC from benign lung diseases. However, the clinical utility of serum BCAR1 as a molecular marker for prognosis in NSCLC or pulmonary tuberculosis requires further clarification and verification.


Assuntos
Biomarcadores Tumorais/análise , Proteína Substrato Associada a Crk/análise , Pneumopatias , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pneumopatias/sangue , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Sensibilidade e Especificidade
10.
World J Gastroenterol ; 17(4): 478-87, 2011 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-21274377

RESUMO

AIM: To investigate the anti-tumor effects of nuclear factor-κB (NF-κB) inhibitor SN50 and related mechanisms of SGC7901 human gastric carcinoma cells. METHODS: MTT assay was used to determine the cytotoxic effects of SN50 in gastric cancer cell line SGC7901. Hoechst 33258 staining was used to detect apoptosis morphological changes after SN50 treatment. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after SN50 treatment. Immunofluorescence staining was used to detect the expression of light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Western blotting analysis were used to determine the expression of proteins involved in apoptosis and autophagy including p53, p53 upregulated modulator of apoptosis (PUMA), damage-regulated autophagy modulator (DRAM), LC3 and Beclin 1. We detected the effects of p53-mediated autophagy activation on the apoptosis of SGC7901 cells with the p53 inhibitor pifithrin-α. RESULTS: The viability of SGC7901 cells was inhibited after SN50 treatment. Inductions in the expression of apoptotic protein p53 and PUMA as well as autophagic protein DRAM, LC3 and Beclin 1 were detected with Western blotting analysis. SN50-treated cells exhibited punctuate microtubule-associated protein 1 LC3 in immunoreactivity and MDC-labeled vesicles increased after treatment of SN50 by MDC staining. Collapse of mitochondrial membrane potential Δψ were detected for 6 to 24 h after SN50 treatment. SN50-induced increases in PUMA, DRAM, LC3 and Beclin 1 and cell death were blocked by the p53 specific inhibitor pifithrin-α. CONCLUSION: The anti-tumor activity of NF-κB inhibitors is associated with p53-mediated activation of autophagy.


Assuntos
Transporte Ativo do Núcleo Celular/fisiologia , Apoptose/fisiologia , Autofagia/fisiologia , NF-kappa B/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos/farmacologia , Benzotiazóis/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Humanos , NF-kappa B/antagonistas & inibidores , Peptídeos/farmacologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Tolueno/análogos & derivados , Tolueno/farmacologia , Proteína Supressora de Tumor p53/antagonistas & inibidores
11.
World J Gastroenterol ; 15(40): 5044-52, 2009 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-19859997

RESUMO

AIM: To investigate the effects of class I phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice. METHODS: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment, the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were observed. RESULTS: In this study, we showed that treating the tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% +/- 3.11%, 43.20% +/- 3.27% and 63.28% +/- 2.10% at 5, 10 and 15 d, respectively) along with apoptosis. The expression of MMP-2 was also downregulated (from 71.4% +/- 1.6% to 47.9% +/- 0.7%, 31.9% +/- 0.9% and 7.9% +/- 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% +/- 1.5% to 36.9% +/- 0.4%, 23.5% +/- 0.9% and 7.7% +/- 0.6%), the mean MVD (from 51.2% +/- 3.1% to 41.9% +/- 1.5%, 30.9% +/- 1.7% and 14.9% +/- 0.8%), and the expression of VEGF (from 47.2% +/- 3.1% to 25.9% +/- 0.5%, 18.6% +/- 1.2% and 5.1% +/- 0.9%) by immunohistochemical staining. CONCLUSION: The class I PI3K inhibitor LY294002 could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.


Assuntos
Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica , Morfolinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Animais , Antígenos CD34/biossíntese , Apoptose , Humanos , Imuno-Histoquímica/métodos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Camundongos , Camundongos Nus , Transplante de Neoplasias , Inibidores de Fosfoinositídeo-3 Quinase , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 20(3): 151-4, 2008 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-18328127

RESUMO

OBJECTIVE: To investigate the optimal mean blood pressure of different resuscitation fluids in resuscitating hemorrhagic shock in rats. METHODS: One hundred and eighty Sprague-Dawley (SD) rats were used to reproduce hemorrhagic shock model by 35% and 45% depletion of blood volume, and they were randomly divided into Lactated Ringer solution (LR), 7.5% NaCl/6% Dextran 40 (HSD), and LR+hydroxyethyl starch (HES) groups. Mean arterial pressure (MAP) was maintained at 60, 80 and 100 mm Hg (1 mm Hg=0.133 kPa) respectively with these fluids. Left intraventricular systolic pressure (LVSP), the maximal change rate of left intraventricular pressure (+/-dp/dt max), blood gases and 12-hour survival rate were observed. RESULTS: In 35% hemorrhagic shock rats, LR and LR+HES could better maintain the MAP at the set level, but HSD could not maintain MAP at 100 mm Hg, reaching only 85 mm Hg. In 45% hemorrhagic shock rats, LR and HSD, also could not elevate MAP to 100 mm Hg, and LR infusion could restore MAP to about 85 mm Hg, HSD to 80 mm Hg and LR+HES to 60 mm Hg. Overall 12-hour survival rate was highest in group with LR+HES to maintain MAP at 60 mm Hg with satisfactory hemodynamic parameters and blood gases. HSD group ended up with a lowest survival rate. CONCLUSION: Different fluids to resuscitate hemorrhagic shock showed a different optimal MAP. LR between 85-100 mm Hg, HSD at 80 mm Hg and LR+HES at 60 mm Hg, may throw better effect on resuscitating moderate and severe hemorrhagic shock.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Substitutos do Plasma/farmacologia , Ressuscitação , Choque Hemorrágico/fisiopatologia , Animais , Pressão Sanguínea/fisiologia , Dextranos/farmacologia , Modelos Animais de Doenças , Feminino , Derivados de Hidroxietil Amido/farmacologia , Soluções Isotônicas/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Lactato de Ringer , Choque Hemorrágico/terapia
13.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 16(8): 473-6, 2004 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-15298803

RESUMO

OBJECTIVE: To investigate the mechanism of better result of limited resuscitation in a model of uncontrolled hemorrhagic shock. METHODS: Uncontrolled hemorrhagic shock was produced in 54 rats by a standardized massive splenic injury with transection of the middle branch of splenic artery (MSIA). The rats were randomly assigned to six groups (n=6) by maintenance of the level of mean arterial pressure (MAP): sham-operated group (SS), 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) and 100 mm Hg (RS100, 1 mm Hg=0.133 kPa). When the MAP reached 40 mm Hg, resuscitation was begun. Ringer's solution was continued as needed to maintain the following desired endpoints for 45 minutes (T45 point): MAP of 40, 50, 60, 80 and 100 mm Hg. After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to raise the MAP to 100 mm Hg for 120 minutes (T165 point), followed by a 240 minutes observation period (T405 point). All animals were observed for 240 minutes or till death. The blood samples were withdrawn from artery for hematocrit (Hct), blood lactate (BL), base excess(BE) at T0, T45, T165, T405 points. At the end of the experiment, a small amount of hepatic tissue was collected for measuring tissue blood perfusion, total antioxidative capacity (T-AOC), Na(+)-K(+)-ATPase, and malondialdehyde (MDA). RESULTS: At T45, T405 points, Hct in SS, RS50 and RS60 were significantly higher than in RS80 and RS100(P<0.05). At T405 point, BL and BE levels in RS80 and RS100 were significantly higher than that of the other groups (P<0.05). The contents of MDA in SS, RS40, and RS50 were significantly lower than in RS80 and RS100(P<0.05). T-AOC level, Na(+)-K(+)-ATPase were significantly lower in RS80 and RS100 than that in the other groups. Blood perfusion was significantly lower in RS80 and RS100 than that in SS, RS40, and RS50. CONCLUSION: In the setting of uncontrolled hemorrhagic shock, limited resuscitation could balance well the needs of organ perfusion and decrease lactate level. It might also exert a protective effect against ischemia/reperfusion injury to liver tissue.


Assuntos
Hidratação/métodos , Ressuscitação/métodos , Choque Hemorrágico/fisiopatologia , Animais , Modelos Animais de Doenças , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/fisiopatologia , Choque Hemorrágico/etiologia , Choque Hemorrágico/terapia
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