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1.
China Pharmacy ; (12): 155-159, 2024.
Article in Chinese | WPRIM | ID: wpr-1006171

ABSTRACT

OBJECTIVE To investigate the improvement effects of azithromycin on bronchopulmonary dysplasia (BPD) in neonatal rats based on hypoxia-inducible factor-1α(HIF-1α)/HIF-2α/vascular endothelial growth factor (VEGF) pathway. METHODS Sixty newborn SD rats were randomly divided into negative control group (NC), BPD group, azithromycin group and budesonide group (positive control), with 15 rats in each group. Rats in NC group were given normal breathing air, while rats in other three groups were exposed to high-concentration oxygen for 14 days to establish BPD rat models. After successful modeling, rats in azithromycin group were intraperitoneally injected with azithromycin 200 mg/kg, and rats in budesonide group were atomized with budesonide 1.5 mg/kg once a day for 14 consecutive days, while rats in BPD group and NC group were not treated. Pathological changes of lung tissue, radial alveolar count and mean alveolar intercept of rats were observed in each group. The white blood cell count in bronchoalveolar lavage fluid (BALF) and the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were detected; mRNA and protein expressions of VEGF, HIF-1α, HIF-2α were also detected. RESULTS Compared with NC group, the lung tissue in BPD group was obviously damaged; the white blood cell count, average alveolar intercept and the levels of TNF-α, IL-6, IL-1β and MDA were significantly increased; the radial alveolar count, SOD and CAT levels, the relative expressions of VEGF, HIF-1α, HIF-2α mRNA and protein were significantly decreased (P<0.05). Compared with BPD group, the changes of the above indexes in azithromycin group and budesonide group were significantly reversed (P<0.05). CONCLUSIONS Azithromycin can obviously improve the symptoms of BPD in rats, reduce inflammation and oxidative stress, and exert lung protection, the mechanism of which may be realized by activating HIF-1α/HIF-2α/VEGF pathway.

2.
Chinese Journal of Neonatology ; (6): 452-456, 2022.
Article in Chinese | WPRIM | ID: wpr-955277

ABSTRACT

Objective:To study the effects of endothelial progenitor cells (EPC)-derived exosomes on hyperoxia-induced injury in type Ⅱ alveolar epithelial cell (AECⅡ) in neonatal rats.Methods:EPCs of rats were cultured and exosomes were collected using Total Exosome Isolation kit. Primary cultured AECⅡof neonatal rats were randomly assigned into three groups: the control group, the hyperoxia group and the exosome group. The control group was cultured in room air with 5%CO 2, the hyperoxia group was cultured in 95%O 2 with 5%CO 2 and the exosome group was cultured with 0.1 mg/ml EPC-derived exosomes in 95%O 2 with 5%CO 2. Cell viability was detected using cell counting kit-8 (CCK-8) and apoptosis was detected using flow cytometry on d2, d4, and d6. Results:EPC-derived exosomes isolated from EPC culture supernatant were confirmed morphologically using transmission electron microscopy. After co-incubation of Dil-labeled EPC-derived exosomes with AEC Ⅱ for 24 h, Dil fluorescence was detected in the cytoplasm of AEC Ⅱ, indicating exosomes were uptaken by AEC Ⅱ. Compared with the control group, hyperoxia decreased cell viability and increased apoptosis of AEC Ⅱ and the injury was aggravated with the prolongation of hyperoxia duration ( P<0.001). Cell injury in the exosome group was milder than the hyperoxia group ( P<0.001). Compared with the control group, cell viability on d4 and d6 of hyperoxia was lower ( P=0.029 and 0.005 respectively) and cell apoptosis at d6 of hyperoxia was higher in the exosome group ( P=0.007). Conclusions:EPC-derived exosomes may partially attenuate hyperoxia-induced cell injury in neonatal rat AEC Ⅱ.

3.
Chinese Journal of Neonatology ; (6): 54-59, 2020.
Article in Chinese | WPRIM | ID: wpr-865206

ABSTRACT

Objective To study the protective effects and preliminary mechanisms of endothelial progenitor cells-derived microvesicles (EPC-MVs) on hypoxic-ischemic brain damage (HIBD) in newborn rats by using the HIBD model.Method Rat endothelial progenitor cells (EPCs) were cultured and microvesicles were extracted from EPCs culture medium by ultracentrifugation.A total of 60 neonatal SD rats were randomly assigned into control group,HIBD group,saline group and EPC-MVs group.The HIBD model was prepared in HIBD group,saline group and EPC-MVs group.After the preparation of the HIBD model,rats in saline group and EPC-MVs group received intraventricular injection with saline and EPC-MVs,respectively.After 72 hours,the rats were sacrificed for brain tissue,cerebral infarction was detected by TTC staining,vascular endothelial growth factor (VEGF) mRNA was tested by real-time PCR,protein western blot was used to detect changes in VEGF protein expression.Result Cells extracted and cultured from the spleen of 12-week-old SD rats were confirmed as EPCs by morphology and flow cytometry.EPC-MVs isolated by high-speed centrifugation from EPCs culture supernatant met the morphological characteristics of microvesicles by transmission electron microscopy.The infarcted brain tissue was not detected in the control group.The cerebral infarction volume ratios of HIBD group,saline group and EPC-MVs group were (80.3 ± 6.3) %,(77.9 ± 8.9) %,(35.2 ± 7.7) %,respectively.The infarct volume of EPC-MVs group was significantly lower than that of HIBD group and saline group (P < 0.001).The expression of VEGF mRNA and protein in HIBD group,saline group and EPC-MVs group were higher than those in control group (P <0.001).Among them,EPC-MVs group had the most significant increase,compared with the other three experimental groups,and the difference was statistically significant (P < 0.001).There was no significant difference between saline group and HIBD group in the expression of VEGF mRNA and protein (P > 0.05).Conclusion Intraventricular injection of EPC-MVs can attenuate HIBD in neonatal rats,and the mechanism may be related to up-regulation of VEGF expression.

4.
Chinese Journal of Applied Clinical Pediatrics ; (24): 114-117, 2015.
Article in Chinese | WPRIM | ID: wpr-466794

ABSTRACT

Objective To explore the effectiveness and adverse effect of high frequency oscillation ventilation (HFOV) combined with Sildenafil (SIL) treatment on newborns with persistent pulmonary hypertension (PPHN).Methods A total of 89 cases of PPHN infants collected from Chengdu Women and Children's Central Hospital from Sep.2010 to Sep.2012 were randomly divided into HFOV group,constant mechanical ventilation (CMV) group,HFOV combined SIL group (HFOV + SIL group) and CMV combined with SIL group (CMV + SIL group).The arterial blood gas,pulmonary artery pressure (PAP) and adverse reactions were monitored before and 3 days after treatment.SNK multiple comparison method andx2 test were performed for data before and after treatment among groups for continuous variables and categorical variables,respectively.Results The levels of pa (O2) [(79.1 ± 13.7) mmHg (1 mmHg =0.133 kPa),(77.9 ±14.6) mmHg,(85.4 ±15.2) mmHg],Sa(O2) [(87.8 ±13.4)%,(88.4±15.6)%,(96.1±15.9)%],pa(CO2)[(42.5±11.3) mmHg,(40.2 ±10.5) mmHg,(35.6 ±8.7) mmHg] and PAP [(31.1 ± 8.1) mmHg,(30.4 ± 9.5) mmHg,(25.8 ± 7.3) mmHg] were all improved significantly in CMV + SIL group,HFOV group and HFOV + SIL group compared with those in CMV group[(69.9 ± 12.3) mmHg,(81.1 ± 14.9)%,(48.1 ±9.5) mmHg,(35.6 ±8.9) mmHg] (F =4.629 3,3.673 2,5.865 3,4.849 5,P <0.05),especially for HFOV + SIL group(P < 0.05).No significant difference in such indicators was observed between CMV + SIL group and HFOV group (P > 0.05).The effective rate in HFOV + SIL group (90%) was the highest among the 4 groups (x2 =7.938,P < 0.05).During the treatment,all neonates have no adverse reaction.Conclusion The combined use of SIL and HFOV might be a more effective and safer method in the treatment of PPHN of neonate.

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