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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(2): 159-64, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-26903064

RESUMO

OBJECTIVE: To investigate the correlation between uncoupling protein 2 (UCP2) expression and myocardial mitochondria injury in rats with sepsis induced by lipopolysaccharide (LPS). METHODS: The rat model of sepsis was established through an intraperitoneal injection of LPS. Forty male Sprague-Dawley rats were randomly and equally divided into control group (an intraperitoneal injection of normal saline), sepsis 6 h group (LPS-6 h group), sepsis 12 h group (LPS-12 h group), sepsis 24 h group (LPS-24 h group), and sepsis 48 h group (LPS-48 h group). The serum and heart tissues were harvested at corresponding time points and myocardial mitochondria was extracted. The microplate reader was applied to measure creatine kinase (CK), creatine kinase-MB (CK-MB), and reactive oxygen species (ROS). Flow cytometry was applied to measure the degree of mitochondrial swelling and mitochondrial membrane potential (MMP). Western blot was used to measure the expression level of UCP2. Electron microscopy was applied to observe the morphological changes in heart tissues and myocardial mitochondria. RESULTS: Compared with the control group, the LPS groups had significantly increased serum levels of CK, CK-MB, and myocardial ROS, as well as a significantly increased degree of mitochondrial swelling (P<0.05), and these values reached their peaks at 24 hours after LPS injection. The LPS groups had a significant decrease in MMP (P<0.05), which reached the lowest level at 24 hours after LPS injection. Western blot showed that the LPS groups had a significant increase in the expression level of myocardial UCP2 compared with the control group (P<0.05), which reached its peak at 24 hours after LPS injection. The results of electron microscopy showed mitochondrial swelling, partial rupture of the mitochondrial membrane, and cavity formation in rats in the LPS groups. The most severe lesions occurred in the LPS-24 h group. In rats with LPS, the ROS level in the myocardial mitochondria and the degree of mitochondrial swelling were positively correlated with the expression level of UCP2 (r=0.796 and 0.893, respectively; P<0.05), while MMP was negatively correlated with the expression level of UCP2 (r=-0.903, P<0.05). CONCLUSIONS: In the rat model of sepsis, the myocardium and myocardial mitochondria have obvious injuries, and the expression level of UCP2 is closely correlated with mitochondrial injury. Therefore, UCP2 might play an important role in myocardial mitochondrial injury in sepsis.


Assuntos
Cardiomiopatias/metabolismo , Canais Iônicos/metabolismo , Mitocôndrias Cardíacas/metabolismo , Proteínas Mitocondriais/metabolismo , Sepse/metabolismo , Animais , Cardiomiopatias/genética , Modelos Animais de Doenças , Humanos , Canais Iônicos/genética , Lipopolissacarídeos/efeitos adversos , Masculino , Proteínas Mitocondriais/genética , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Sepse/genética , Proteína Desacopladora 2
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(8): 859-63, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26287353

RESUMO

OBJECTIVE: To preliminarily investigate the long-term structural and functional injuries of mitochondria in rat brain caused by sepsis. METHODS: Wistar rats were randomly assigned into sepsis and control groups. A rat model of sepsis was prepared by an intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) of gram-negative bacteria, and the survival assay was performed. Eight rats in the sepsis group were sacrificed at 12, 24, 48, or 72 hours after LPS injection, while rats in the control group were sacrificed after an intraperitoneal injection of an equal volume of normal saline. Mitochondria were extracted from rat brain tissue. Mitochondrial membrane potential (MMP) and mitochondrial swelling level were determined by flow cytometry, and the activities of electron transport chain complexes (I-V) were measured using enzyme assay kits. Hematoxylin-eosin (HE) staining and electron microscopy were used to observe morphological changes in brain tissue and mitochondria. RESULTS: The sepsis group had a significantly lower survival rate than the control group (P<0.01). The MMP and activities of electron transport chain complexes (I-V) in the sepsis group, which were significantly lower than those in the control group (P<0.05), were reduced to the lowest levels at 48 hours and partially recovered at 72 hours. The mitochondrial swelling level in the sepsis group, which was significantly higher than that in the control group (P<0.05), increased to the peak level at 48 hours and partially recovered at 72 hours. Hematoxylin and Eosin staining revealed substantial damages in the structure of brain tissue, and electron microscopy showed mitochondrial swelling, and vacuolization in a few mitochondria. CONCLUSIONS: In the rat model of LPS-induced sepsis, both structural and functional injuries are found in cerebral mitochondria, and achieve the peak levels probably at around 48 hours.


Assuntos
Encéfalo/fisiopatologia , Lipopolissacarídeos/toxicidade , Mitocôndrias/fisiologia , Sepse/fisiopatologia , Animais , Encéfalo/patologia , Encéfalo/ultraestrutura , Masculino , Potencial da Membrana Mitocondrial , Mitocôndrias/ultraestrutura , Ratos , Ratos Wistar , Sepse/induzido quimicamente , Sepse/mortalidade
3.
Int Immunopharmacol ; 59: 287-294, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29674256

RESUMO

OBJECTIVE: Interleukin-6 (IL-6) is a neuromodulation factor with extensive and complex biological activities. IL-6 has been reported to activate AMPK, while AMPK regulates mitochondrial biogenesis and autophagy. The aim of this study was to investigate the role of IL-6 in mitochondrial biogenesis using astrocytes under experimental septic condition and examined how IL-6/AMPK signaling pathway affected this process. METHODS: The primary cultures of cerebral cortical astrocytes were randomly allocated into six groups: control group, LPS+IFN-γ group, IL-6 group (LPS+IFN-γ+IL-6), C group (LPS+IFN-γ+IL-6+Compound C), siRNA group (LPS+IFN-γ+IL-6+IL-6R siRNA) and siRNA+C group (LPS+IFN-γ+IL-6+IL-6R siRNA+ Compound C). All groups were stimulated for 6 h. Cytokines and reactive oxygen species (ROS) analyses, detection of adenosine triphosphate (ATP), mtDNA content and cell viability, evaluation of the mitochondrial ultrastructure and volume density, western blots of proteins associated with mitochondrial biogenesis and phospho-adenosine monophosphate activated protein kinase (p-AMPK) were performed respectively. RESULTS: Compared with LPS+IFN-γ group, IL-6 group had milder ultrastructural damage of mitochondria, higher mtDNA content and mitochondrial volume density, higher expression of proteins associated with mitochondrial biogenesis (PGC-1α, NRF-1 and TFAM) and p-AMPK, and thus higher cell viability, whereas blocking IL-6/AMPK signaling pathway, the protective effect of IL-6 has been diminished, compared with IL-6 group. CONCLUSION: IL-6 enhances mitochondrial biogenesis in astrocytes under experimental septic condition through IL-6/AMPK signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Astrócitos/metabolismo , Interleucina-6/metabolismo , Mitocôndrias/fisiologia , Sepse/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA Mitocondrial/metabolismo , Interleucina-1beta/genética , Lipopolissacarídeos/farmacologia , Mitocôndrias/ultraestrutura , Biogênese de Organelas , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
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