RESUMO
Tetrahydropalmatine (THP) is the main component of the Chinese medicine Corydalis yanhusuo, which has been reported to alleviate limb ischemia-reperfusion-induced acute lung injury (LIR-ALI). This study aimed to investigate the mechanism underlying the effect of THP on relieving LIR-ALI. LIR-ALI model was established in rats with the presence or absence of THP pretreatment. Then, BEAS-2B cells and THP-1 macrophages were cocultured with rat serum from the Sham group and the Model group in the presence or absence of THP pretreatment. Subsequently, lung/body weight and lung wet/dry ratio of rats were calculated. Histological changes of lung tissues were observed by hematoxylin-eosin staining. Expression of CD86 and CD163 in lung tissues of rats was assessed by quantitative reverse transcription polymerase chain reaction, immunohistochemistry staining, and flow cytometry analysis. Levels of inflammatory cytokines were measured by enzyme linked immunosorbent assay. The expression of proteins related to toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/NLRP3 signaling was detected by western blot analysis. Results revealed that THP significantly relieved LIR-ALI in rats. Moreover, THP also reduced CD86 expression but elevated CD163 expression in lung tissues of rats with LIR-ALI. Furthermore, THP inhibited inflammation in serum and bronchoalveolar lavage fluid of rats with LIR-ALI and inactivated the TLR4/NF-κB/NLRP3 signaling in vivo. Additionally, coculture of serum from rats in the Model group also reduced viability, promoted inflammation, inactivated TLR4/NF-κB/NLRP3 expression in BEAS-2B cells and inhibited macrophage polarization, while these effects were all reversed by THP treatment. Collectively, THP could induce the polarization of M1 macrophage to M2 to suppress inflammation via inhibiting TLR4/NF-κB/NLRP3 signaling, thereby attenuating LIR-ALI.
Assuntos
Lesão Pulmonar Aguda , Traumatismo por Reperfusão , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/etiologia , Animais , Alcaloides de Berberina , Inflamação/patologia , Lipopolissacarídeos/efeitos adversos , Pulmão/metabolismo , Macrófagos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Reperfusão , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Xenon is an elemental anesthetic with nine stable isotopes. Nuclear spin is a quantum property which may differ among isotopes. Xenon 131 (Xe) has nuclear spin of 3/2, xenon 129 (Xe) a nuclear spin of 1/2, and the other seven isotopes have no nuclear spin. This study was aimed to explore the effect of nuclear spin on xenon anesthetic potency. METHODS: Eighty C57BL/6 male mice (7 weeks old) were randomly divided into four groups, xenon 132 (Xe), xenon 134 (Xe), Xe, and Xe groups. Due to xenon's low potency, loss of righting reflex ED50 for mice to xenon was determined with 0.50% isoflurane. Loss of righting reflex ED50 of isoflurane was also measured, and the loss of righting reflex ED50 values of the four xenon isotopes were then calculated. The exact polarizabilities of the isotopes were calculated. RESULTS: Combined with 0.50% isoflurane, the loss of righting reflex ED50 values were 15 ± 4%, 16 ± 5%, 22 ± 5%, and 23 ± 7% for Xe, Xe, Xe, and Xe, respectively. For xenon alone, the loss of righting reflex ED50 values of Xe, Xe, Xe, and Xe were 70 ± 4%, 72 ± 5%, 99 ± 5%, and 105 ± 7%, respectively. Four isotopes had a same exact polarizability of 3.60 Å. CONCLUSIONS: Xenon isotopes with nuclear spin are less potent than those without, and polarizability cannot account for the difference. The lower anesthetic potency of Xe may be the result of it participating in conscious processing and therefore partially antagonizing its own anesthetic potency. Nuclear spin is a quantum property, and our results are consistent with theories that implicate quantum mechanisms in consciousness.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Estado de Consciência/efeitos dos fármacos , Isoflurano/administração & dosagem , Reflexo de Endireitamento/efeitos dos fármacos , Isótopos de Xenônio/administração & dosagem , Animais , Estado de Consciência/fisiologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reflexo de Endireitamento/fisiologiaRESUMO
BACKGROUND: With the aging of human society, more and more elderly patients have to undergo surgery and anesthesia. Clinical observations have indicated from time to time that spinal anesthesia in the elderly appears to last longer than in young people, although there is limited research in this area and the mechanism is unclear at present time. This research work is expected to help understand the decline of local anesthetic metabolism in cerebrospinal fluid of elderly patients so as to help them with precise anesthesia and rapid rehabilitation. METHODS: Twenty patients with spinal anesthesia in orthopedic lower limb surgery were selected to study the rate of drug metabolism in cerebrospinal fluid in two age groups, i.e.,18-30 years old and 75-90 years old. Ropivacaine in peripheral blood is used as a probe to reflect the speed of drug metabolism in cerebrospinal fluid. The contents of total Aß protein and hyaluronic acid in the cerebrospinal fluid were investigated as well. RESULTS: The equivalent dose of ropivacaine anesthetizes the elderly group for a longer time. The metabolism rate of ropivacaine in an elderly patient was slower than that of a young patient. No significant difference in total Aß protein between the two groups was observed while hyaluronic acid in the elderly group was significantly higher than that in the young group. CONCLUSIONS: This study shows that the dose of ropivacaine should be reduced when used for anesthesia in elderly patients. The cumulation of ropivacaine and HA appears to imitate the degeneration of central lymphatic circulation metabolism in elderly people.
RESUMO
Acute respiratory distress syndrome (ARDS) is associated with a mortality of 45%. Our previous research indicated that anti-vascular endothelial growth factor (VEGF) could maintain the normal structure and function of the respiratory barrier. However, systemic application of VEGF antagonists would lead to animal death. This study attempts to study the targeted drug delivery for ARDS. In this study, we used soluble fms-like tyrosine kinase-1 (sFlt)-targeted ultrasound microbubbles to antagonize the effect of VEGF on lung tissue. Ninety male BALB/c mice were randomly assigned to 6 groups: phosphate buffer saline (PBS) group (PBS+PBS); blank group (PBS+empty microbubbles); lipopolysaccharide (LPS) group (LPS+PBS); ARDS group (LPS+empty microbubbles); control group (PBS+sFlt microbubbles); and treatment group (LPS+sFlt microbubbles). After administration of LPS or PBS in the corresponding groups, the sFlt-targeted microbubbles or empty microbubbles were injected into the blood circulation. Then the lungs were irradiated with ultrasound, which ruptured the drug-loaded microbubbles and helped release drugs to the lung tissues targeted. The lung injury score, lung wet/dry ratio (W/D), liver and kidney functions, and the mortality of the mice in all groups were investigated at the predetermined time point. The difference in mortality between groups was examined by Fisher test. Other data were analyzed by one-way analysis of variance (ANOVA). A value of P<0.05 indicates that the difference was significant. The results showed that the PaO2 levels were normal in the PBS group, the blank group, and the control group. The LPS group and ARDS group showed significant hypoxia. PaO2 was improved significantly in the treatment group. The lung injury score and W/D were normal in the PBS group, the blank group, and the control group. The lung injury score and W/D increased significantly in the LPS group and ARDS group and decreased in the treatment group (P<0.05). The mortality rate of the ARDS model was 60% (95% confidence interval 47.5%-72.5%), and that with sFlt-targeted microbubbles was significantly lower at only 40% (95% confidence interval 27.5%-52.5%, P<0.05). It was concluded that anti-VEGF with sFlt targeted ultrasound microbubbles attenuated the lung injury and ultimately reduced the 7-day mortality effectively. It might be a suitable therapeutic tool for the treatment of ARDS.
Assuntos
Lipopolissacarídeos/efeitos adversos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microbolhas , Distribuição Aleatória , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/mortalidade , Resultado do Tratamento , Ondas Ultrassônicas , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/farmacologiaRESUMO
BACKGROUND: Acute respiratory distress syndrome is associated with a mortality of 45%. The authors investigated the possible mechanisms and effect of vascular endothelial growth factor on alveolar epithelial barrier permeability in acute respiratory distress syndrome mice model. METHODS: Eighty Male BALB/c mice were randomly assigned to four group: PBS group, LPS group, sFlt group, or LPS + sFlt group. The levels of vascular endothelial growth factor and total protein in bronchoalveolar lavage fluid were compared, together with lung injury score and the histopathology of alveolar epithelial barrier. The expressions of vascular endothelial growth factor and tight junction proteins mRNA in lung tissue were also studied. RESULTS: Lipopolysaccharide (LPS) inhaling was accompanied with increasing lung vascular endothelial growth factor (VEGF) expression. Anti-VEGF with soluble fms-like tyrosine kinase-1 (sFlt-1) attenuated the lung injury effectively. CONCLUSIONS: Our data indicate that anti-vascular endothelial growth factor with soluble fms-like tyrosine kinase-1 could maintain the normal structure and function of respiratory membrane in acute respiratory distress syndrome mice model and might be a suitable therapeutic tool for the treatment of acute respiratory distress syndrome.