RESUMO
BACKGROUND: Parkinson's disease (PD) is a neurological disorder. Recently, celastrol (Cel) has been reported to have neuroprotective properties. We investigated the protective effects of Cel on PD in a cell model with 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and further addressed the underlying protective mechanisms of Cel. METHODS: PC12 cells were treated with 6-OHDA, and Cel was added to the medium at various concentrations. The CCK-8 assay, Hoechst/PI staining, and flow cytometry analysis were performed to detect cellular viability and apoptosis. Mitochondrial membrane potential (MMP) was examined by JC-1 staining. ROS level was quantified by ROS staining. The effects of Cel on the expression of miR-146a and PI3K/Akt/mTOR pathway were then clarified using real-time PCR and Western blotting. Moreover, a miR-146a mimic was synthesized and transfected into PC12 cells to further determine the mechanisms of Cel's neuronal protection against 6-OHDA-induced neurotoxicity. RESULTS: Cel greatly improved cell viability and lessened apoptosis. Flow cytometry showed that Cel especially inhibited early apoptosis. Cel also obviously restored the MMP and decreased ROS level destroyed by 6-OHDA. Moreover, 6-OHDA increased the expression of miR-146a and decreased pAkt/mTOR protein levels, whereas Cel reversed these changes. In particular, miR-146a targeted and inhibited the expression of PI3K, an upstream molecule of Akt/mTOR. Transfection of 6-OHDA-treated neurons with miR-146a mimic notably attenuated Cel's protective effects. LIMITATIONS: There were no animal experiments in our study. CONCLUSIONS: Cel exerts neuroprotective activity against 6-OHDA-caused neurotoxicity by regulating miR-146a/PI3K/Akt/mTOR pathway, which provides a potential application of Cel for treating neurodegenerative diseases.
Assuntos
Neoplasias das Glândulas Suprarrenais , MicroRNAs , Fármacos Neuroprotetores , Doença de Parkinson , Feocromocitoma , Animais , Apoptose , MicroRNAs/genética , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Triterpenos Pentacíclicos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Espécies Reativas de Oxigênio , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVE: To investigate the effect of a nursing protocol based on the KABP (Knowledge, Attitude, Belief and Practice) model in the cardiac rehabilitation (CR) of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). METHODS: In this prospective study, a total of 76 patients with AMI who underwent PCI were selected as the research objects. Through random number table, the participants were divided into 41 cases in the KABP group (cardiac rehabilitation nursing based on KABP model) and 35 cases in the control group (conventional rehabilitation nursing). All patients underwent echocardiography within 48 hours after PCI and 3 months after the postoperative follow-up to determine the improvement of their cardiac function. The risk of falling out of bed for 7 days after surgery, the physical improvement and exercise endurance before and after the intervention, as well as the scores of Coronary Artery Disease Self-Management Scale (CSMS) and China Questionnaire of Quality of Life in Patients with Cardiovascular Diseases (CQQC) were compared between the two groups. RESULTS: Within 48 hours after operation, there was no significant difference in the indicators of cardiac function between the two groups (all P>0.05). After 3 months of postoperative follow-up, the improvement of cardiac function of KABP group including left ventricular ejection fraction, stroke volume, and cardiac index were significantly better than those of the control group (all P<0.05), and NYHA class was also significantly better than that of the control group (P<0.001). On the 7th day after operation, the high risk of falling out of bed in the KABP group (17.07%) was significantly lower than that in the control group (74.29%; P<0.001). The metabolic equivalent, 6-minute walk test scores, and CQQC scores of the KABP group were significantly higher than those of the control group (all P<0.01). The total scores of daily life management, disease medical management, emotional cognitive management and self-management in CSMS were significantly higher than those of the control group (all P<0.01). CONCLUSION: Cardiac rehabilitation care based on the KABP model can improve the recovery of cardiac function of AMI patients after PCI, reduce the risk of falling out of bed, help patients recover their physical status and exercise endurance, and improve their management behavior and postoperative life quality.
RESUMO
BACKGROUND: Lead exposure during pregnancy contributes to fetal abortion and/or teratogenesis. Endoplasmic reticulum (ER) apoptosis can be induced by various pathological conditions when ER function is disturbed. However, it is unclear whether ER stress and apoptosis play a role in the etiology of lead-exposed disease status. We aimed to investigate whether lead induced placental apoptosis and subsequent toxicity is initiated by ER apoptosis via caspase-12. METHODS: Sixty-three female Wistar rats were exposed to lead in drinking water during various gestational periods. Blood lead level was determined by atomic absorption spectrophotometry. Placental cytoplasmic organelles were examined by electronic microscopy. Placental caspase-12 mRNA expression was evaluated by qRT-PCR. TUNEL assay was used to determine the placental apoptosis. RESULTS: Lead exposure significant induced ER apoptosis compared to that of the controls (P < 0.05), accompanied with increased caspase-12 mRNA expression. Significant differences of caspase-12 mRNA expression levels were observed among the four groups (F = 13.78, P < 0.05). Apoptotic index (AI) was significantly increased in experimental groups compared to that of the controls (F = 96.15, P < 0.05). In lead-exposed groups, trophoblast cells underwent degeneration and fibrin deposition; Mitochondria were swollen and decreased in number; ER swelling, expansion, and vacuolization were observed. CONCLUSION: Lead exposure contributes to placental apoptosis, as well as increased caspase-12 mRNA expression, which in turn promoted ER stress.