RESUMEN
In this study, MicroRNA-210 (miR-210), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse myocardium ischemia/reperfusion (I/R) injury. miR-210 was increased in cardiomyocytes exposed to hypoxia/reoxygenation (H/R). The expression of IL-6 and TNF-α in both serum and supernatant were reduced in miR-210 mimics groups. Mice were randomly divided into four groups, which were pre-treated with saline (sham and ischemia/reperfusion group), miR-210 mimics and miR-210 inhibitor treatments. Three days later, the mouse IR model was established by ischemia for 30 min, followed by reperfusion for 3 h. Myocardium and plasma were harvested and assessed. The myocardium histopathological changes were reduced in miR-210 mimics groups, and serum levels of Creatine kinase isoenzyme (CK-MB) and Lactate dehydrogenase (LDH) were significantly decreased compared with I/R groups. The protein expression of proinflammatory factor interleukin (IL)-1ß and IL-6 were suppressed by the up-regulation of miR-210. The expression of miR-210 was negatively correlated with the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In conclusion, our study indicates that miR-210 protects heart from myocardium I/R injury via suppressing NF-κB signal pathway.
Asunto(s)
MicroARNs , Daño por Reperfusión Miocárdica , Daño por Reperfusión , Animales , Ratones , MicroARNs/genética , Daño por Reperfusión Miocárdica/genética , Miocitos Cardíacos , FN-kappa B/genética , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: The aim of this study was to investigate the effects of oxaliplatin on intestinal floras, inflammation level, apoptosis-related gene expressions and oxidative stress in rats with colorectal cancer. MATERIALS AND METHODS: A total of 30 adult Sprague-Dawley (SD) rats were selected as research objects and were divided into control group, model group and oxaliplatin group. Rats in control group were raised normally, without any treatment. Rats in model group were subcutaneously injected with dimethylhydrazine (25 mg/kg) to establish the model of colorectal cancer. Meanwhile, rats in oxaliplatin group were injected with oxaliplatin (15 mg/kg) once every 2 weeks for 12 consecutive weeks. Peripheral blood, intestinal tumor tissues and feces were collected from rats. In addition, inflammatory indexes [tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-4 (IL-4) and IL-1ß], oxidative stress indexes [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and total antioxidant capacity (T-AOC)], expressions of apoptosis-related genes [apoptotic protease activating factor-1 (Apaf1), Caspase-9, Survivin and B-cell lymphoma-2 (Bcl-2)] and intestinal floras were detected. RESULTS: The abundance of microorganisms such as Sphaerobacterales, Adlercreutzia and Coriobacterium glomerans increased significantly in the intestines in control group (p<0.05). However, the abundance of Bifidobacterium, Rikenellaceae and Paraprevotella in the intestines was obviously higher in model group (p<0.05). Oxaliplatin group exhibited remarkably higher abundance of such microorganisms as Cyanobacteria, Alistipes and Metascardovia in rat intestines (p<0.05). The content of Alistipes was the highest in oxaliplatin group, followed by control group and model group, and the difference was statistically significant (p<0.05). The levels of serum TNF-α, CRP and IL-1ß were remarkably higher in model group than those in control group (p<0.05). Oxaliplatin group exhibited notably lower levels of serum TNF-α, CRP and IL-1ß (p<0.05) and higher IL-4 level than model group (p<0.05). The content of serum CAT, SOD, GSH and T-AOC was markedly elevated in model group compared with control group (p<0.05). However, it was significantly reduced in oxaliplatin group in comparison with model group (p<0.05). Compared with control group, model group had distinctly lower expressions of Apaf1, Caspase-9 and Survivin but an evidently higher expression level of Bcl-2 in tumor tissues (p<0.05). Moreover, the expressions of Apaf1, Caspase-9 and Survivin were clearly higher, while that of Bcl-2 was prominently lower in tumor tissues in oxaliplatin group than model group (p<0.05). CONCLUSIONS: Oxaliplatin exerts significant effects on the inflammation, oxidative stress, apoptosis-related genes and intestinal floras in rats with CRC.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación/tratamiento farmacológico , Oxaliplatino/farmacología , Animales , Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/metabolismo , Modelos Animales de Enfermedad , Inflamación/metabolismo , Masculino , Oxaliplatino/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To detect the change in miRNA-210 expression of cardiomyocytes under hypoxia/reoxygenation status. Also, the effect of miR-210 on the apoptosis of cardiomyocytes induced by oxygen-glucose deprivation/reperfusion (OGD/R) and its mechanism through establishing the OGD/R injury model of primary cardiomyocytes in this experiment were investigated. MATERIALS AND METHODS: The cell model of OGD/R injury was established. The cell apoptosis in each group was detected by methyl thiazolyl tetrazolium (MTT) assay and detection of Caspase-3 activity. The change in miR-210 expression in each group was detected by Real-time fluorescence quantitative polymerase chain reaction (PCR). The high-expression and low-expression miR-210 models were established through the transient transfection of miR-210 mimic and inhibitor to detect the relevant indexes of cell apoptosis. At the same time, changes in mRNA and protein expressions of E2F3 were detected by RT-PCR and Western blotting, respectively. The E2F3 overexpression vector was constructed, and the overexpression vector plasmid and miR-210 mimic were jointly transfected into the cells to detect the relevant indexes of cell apoptosis. RESULTS: After OGD/R treatment, the activity of Caspase-3 was increased, the survival of cardiomyocytes was significantly inhibited and the expression level of miR-210 was up-regulated in OGD/R injury. Transfection of miR-210 mimic for miR-210 overexpression could alleviate the OGD/R-induced cardiomyocyte injury, while the decrease of miR-210 expression could aggravate the apoptosis of cardiomyocytes. In addition, the high expression of miR-210 could inhibit the protein expression of E2F3, and co-transfection of E2F3 plasmid and miR-210 mimic could reverse the inhibiting effect of miR-210 on the apoptosis of cardiomyocytes. CONCLUSIONS: We confirmed that miR-210 can inhibit the OGD/R-induced apoptosis of cardiomyocytes, and miR-210, as an upstream factor, plays a protective role in cardiomyocytes through directly inhibiting the protein expression of its target gene E2F3.