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Aging (Albany NY) ; 16(8): 6937-6953, 2024 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643461

RESUMO

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.


Assuntos
Ácido Ascórbico , Autofagia , Traumatismos Cardíacos , Miocárdio , Sepse , Animais , Ratos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Autofagia/efeitos dos fármacos , Traumatismos Cardíacos/tratamento farmacológico , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Sepse/complicações , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
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