Mian Zeng

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (9)13.02 Total impact

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    ABSTRACT: Alveolar macrophages (AMs) undergo increased apoptosis during sepsis-induced acute respiratory distress syndrome (ARDS). Ghrelin exhibits an antiapoptotic effect in several cell types and protects against sepsis-induced ARDS in rats; however, the molecular mechanisms underlying this antiapoptotic effect remain poorly understood. In this study, we first examined the antiapoptotic effect of ghrelin on lipopolysaccharide (LPS)-stimulated AMs in vitro. In AMs, growth hormone secretagogue receptor 1a (GHSR-1a), the ghrelin receptor, was expressed, and treatment of AMs with ghrelin markedly reduced LPS-induced apoptosis, mitochondrial transmembrane potential (ΔΨm) decrease and cytochrome c release. These effects of ghrelin were mediated by GHSR-1a, because a GHSR1-a-targeting siRNA abolished the antiapoptotic action of ghrelin. LPS treatment activated the c-Jun N-terminal kinase (JNK) signaling pathway but inhibited the Wnt/β-catenin pathway. Interestingly, combined LPS-ghrelin treatment reduced JNK activation and increased Wnt/β-catenin activation. Furthermore, like ghrelin treatment, the addition of the JNK inhibitor SP600125 or the GSK-3β inhibitor SB216763 rescued AMs from apoptosis. We also demonstrated that ghrelin altered the balance of Bcl-2-family proteins and inhibited caspase-3 activity. Next, we investigated whether ghrelin protected against septic ARDS in vivo. Sepsis was induced in male rats by performing cecal ligation and puncture; administration of ghrelin reduced sepsis-induced AM apoptosis, pulmonary injury, protein concentrations in the bronchoalveolar lavage fluid, the lung neutrophil infiltration and wet-to-dry weight ratio. However, administration of a specific ghrelin-receptor antagonist, [D-Lys-3]-GHRP-6, abolished the beneficial effects of ghrelin. Collectively, our results suggest that ghrelin exerts anantiapoptotic effect on AMs at least partly by inhibiting JNK and activating the Wnt/β-catenin pathway, and thereby helps alleviate septic ARDS in rats.
    Endocrinology 10/2014; · 4.72 Impact Factor
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    ABSTRACT: Apoptosis of alveolar macrophages (AMs) plays a pathogenic role in acute lung injury (ALI) and its severe type, acute respiratory distress syndrome (ARDS). Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and eliminating cellular injury. We investigated the effects of rat bone marrow mesenchymal stem cells (BMSCs) on lipopolysaccharide (LPS)-induced apoptosis in AMs using transwell experiments, and examined the underlying mechanisms LPS induced AMs apoptosis in a dose- and time-dependent fashion, whereas BMSCs reduced AMs apoptosis when co-cultured at appropriate ratios. BMSCs decreased expression of cleaved caspase-3 and the pro-apoptotic protein, Bax, whilst increased levels of the anti-apoptotic protein, Bcl-2, prolonging the lifespan of AMs in vitro. Promotion of AMs survival by BMSCs required down-regulation of p-GSK-3β and β-catenin in AMs. The anti-apoptosis action of BMSCs was reversed by SB216763, a specific inhibitor of GSK-3β that also activates Wnt/β-catenin signaling. In conclusion, BMSCs can attenuate AM apoptosis partially by suppressing the Wnt/β-catenin pathway.
    Cell Biology International 09/2014; · 1.64 Impact Factor
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    ABSTRACT: This study investigated the effect of ghrelin on oxidative stress in septic rat lung tissue. Male Sprague-Dawley rats were divided into sham-operation, sepsis, and ghrelin groups. Sepsis was induced by cecal ligation and puncture. Ghrelin was administered intraperitoneally at 3 and 15 h post-operation. Bronchoalveolar lavage was performed to collect alveolar macrophages (AMs). Inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression in alveolar macrophages and iNOS protein levels were measured by reverse transcription PCR (RT-PCR) and Western blot. Pulmonary pathology was analyzed and nitrotyrosine expression was examined by immunohistochemistry. Plasma superoxide dismutase (SOD) and lung wet/dry weight were measured. In the sepsis group, iNOS mRNA expression in AMs was 1.33 ± 0.05, 1.44 ± 0.08, and 1.57 ± 0.11 at 6, 12, and 20 h post-surgery, respectively, and were higher compared with the sham-operation group (p < 0.05). No increase was observed at longer time points. iNOS mRNA expression in the sepsis group was lower compared with the ghrelin group (2.27 ± 0.37) (p < 0.05) at 20 h post-surgery. iNOS protein levels in the ghrelin group (0.87 ± 0.03, p < 0.05) were lower than in the sepsis group at 20 h. Ghrelin group pathological scores were lower than in the sepsis group (p < 0.05). Plasma SOD was slightly non-significantly decreased in the ghrelin group. No difference was observed in lung wet/dry weight ratios between sepsis and ghrelin groups. iNOS mRNA expression in AMs was elevated between 6 and 20 h after cecal ligation and puncture (CLP), but did not progress. Ghrelin attenuated pulmonary iNOS protein expression and tended to increase plasma SOD activity. Ghrelin suppressed pulmonary nitrosative stress in septic rats, but did not improve lung wet/dry weight ratios.
    Inflammation 07/2014; · 2.46 Impact Factor
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    ABSTRACT: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress. Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]). MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]). Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 01/2013; 20(1):35-41. · 1.29 Impact Factor
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    ABSTRACT: To observe the effects of rosiglitazone (RSG) and ceftazidime (CAZ) on peroxisome proliferator activated receptor γ (PPARγ) activity in nucleated cells and interleukin (IL-4, IL-6) levels in plasma in septic rats. According to randomized digital table, 180 male Sprague-Dawley (SD) rats were assigned to control group, sham operation group, sepsis group, CAZ group, RSG group and combined CAZ and RSG group. Sepsis model was established by cecal ligation and puncture (CLP). Drugs were administered by intraperitoneal injection at 3-hour post-operation, once every 12-hour. The PPARγ activity in nucleated cells and IL-4, IL-6 levels in plasma were detected by enzyme linked immunosorbent assay (ELISA) at 12, 24 and 48 hours post-operation. There was no difference in PPARγ activity and levels of IL-4 and IL-6 at each time point post-operation between control group and sham operation group. Compared with control group and sham operation group, PPARγ activity [absorbance (A) value] in nucleated cells in sepsis group, where downward trend was seen as time went on, significantly reduced (0.263±0.017 vs. 0.292±0.005, 0.294±0.007, both P<0.05). PPARγ activity was significantly higher in CAZ group, RSG group and CAZ + RSG group than in sepsis group (0.282±0.008, 0.336±0.020, 0.347±0.007 vs. 0.263±0.017, all P<0.05), CAZ + RSG group>RSG group >CAZ group (both P<0.05). Plasma IL-6 and IL-4 levels were higher in sepsis group than in control group and sham operation group (IL-6: 436.77±62.28 ng/L vs. 45.11±10.42 ng/L, 42.28±7.54 ng/L; IL-4: 89.24±25.06 ng/L vs. 41.34±7.08 ng/L, 41.49±7.27 ng/L, all P<0.05) and reached peak at 24 hours and 48 hours post-operation, respectively. Compared with sepsis group, IL-6 and IL-4 levels in CAZ group, RSG group and CAZ + RSG group were significantly decreased (IL-6: 273.48±12.13 ng/L, 317.64±14.10 ng/L, 253.94±13.57 ng/L vs. 436.77±62.28 ng/L; IL-4: 59.12±7.03 ng/L, 68.37±8.28 ng/L, 53.81±8.34 ng/L vs. 89.24±25.06 ng/L, all P<0.05), CAZ + RSG group <CAZ group <RSG group (all P<0.05). In septic rats, PPARγ activity in nucleated cells was decreased. On the basis of effective antibiotic treatment, RSG might play a role in improving PPARγ activity in nucleated cells and reducing the levels of inflammation mediators and anti-inflammatory in plasma.
    Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 09/2012; 24(9):550-3.
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    ABSTRACT: To observe the relationship between activity of peroxisome proliferator activated receptor γ (PPARγ) in nucleated cell and level of pro-inflammatory mediator interleukin-6 (IL-6) in plasma of rats with sepsis. According to the random number table, 90 male Sprague-Dawley (SD) rats were randomly divided into three groups, namely control group, sham operation group and sepsis group. Each group was further divided into three subgroups according to postoperative time points, i.e. 12, 24 and 48-hour subgroups. Each subgroup consisted of 10 rats. Sepsis was reproduced by cecal ligation and puncture (CLP). The PPARγ activity in nucleated cells and IL-6 level in plasma were detected by enzyme-linked immunosorbent assay (ELISA). The PPARγ activity in nucleated cells was significantly decreased at 12, 24 and 48 hours in sepsis group (A value: 0.279±0.004, 0.264±0.009, 0.245±0.012) compared with control group (0.292±0.007, 0.293±0.004, 0.293±0.005) and sham operation group (0.295±0.008, 0.295±0.006, 0.294±0.007), while the IL-6 level was significantly increased in sepsis group (ng/L: 365.25±15.53, 507.16±20.86, 437.89±25.09) compared with control group (43.54±11.10, 48.82±10.62, 42.96±9.52) and sham operation group (42.43±6.77, 40.32±6.48, 44.10±9.36, all P<0.05). When septic condition became worse, the PPARγ activity in nucleated cells of sepsis group lowered, and IL-6 level was gradually elevated after operation, reaching the peak at 24 hours, and then gradually lowered, and the difference of the value between any two time points was all statistically significant (all P<0.05). There was a negative correlation between the PPARγ activity in nucleated cells and IL-6 level in 12-hour subgroup of sepsis group (r=-0.703, P=0.023). In septic rats, the PPARγ activity in nucleated cells was lowered while the pro-inflammatory mediator IL-6 level in plasma elevated, and there was a negative correlation between PPARγ activity and IL-6 level.
    Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 05/2011; 23(5):302-4.
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    ABSTRACT: Backgrounds: Although some recent studies have demonstrated the important role of tumor necrosis factor-α (TNF-α) and soluble TNF receptors (sTNF-R) in inflammation of chronic obstructive pulmonary disease, the exact roles of TNF-α and sTNF-R as well as their interaction remained unclear. Objectives: To study changes in levels of systemic and airway local TNF-α and sTNF-R (sTNF-R55, sTNF-R75) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and clarify the relationship between these mediators and airflow limitation in AECOPD patients. Methods: TNF-α, sTNF-R55 and sTNF-R75 levels in induced sputum and plasma as well as lung functions were examined in 48 AECOPD patients before and after treatment. Samples from 28 healthy volunteers served as controls. Results: Compared to healthycontrols, both pre- and posttreatment levels of TNF-α, sTNF-R55 and sTNF-R75 in induced sputum and plasma of COPD patients were higher. In patients with AECOPD, posttreatment TNF-α levels significantly decreased compared to pretreatment levels (0.6 ± 0.46 vs. 0.82 ± 0.35 μg/l in plasma, p < 0.01; 0.48 ± 0.27 vs. 0.82 ± 0.34 μg/l in sputum, p < 0.001). While posttreatment sTNF-R55 and sTNF-R75 levels increased in both kinds of samples, mediator levels in plasma and lung functions were unrelated (p > 0.05). sTNF-R55 and sTNF-R75 levels in induced sputum were positively correlated with lung functions (p < 0.05), while TNF-α levels were negatively correlated with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to FEV(1) predicted value. Conclusions: Inflammatory and anti-inflammatory mediators were imbalanced in the airways of AECOPD patients. It was local inflammation but not systemic inflammation that was closely related to airflow limitation.
    Respiration 03/2009; 78(4):399-403. · 2.92 Impact Factor
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    ABSTRACT: To study changes in the levels of systematic and airway local oxidative stress in patients in different stages of chronic obstructive pulmonary diseases (COPD), and explore the association between oxidative stress and glucocorticoid receptor (GR) level in the peripheral blood leukocytes. The levels of malonaldehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in induced sputum and plasma, as well as GR levels in peripheral blood leukocytes and plasma levels of cortisol and adrenocorticotrophic hormone (ACTH), were examined in 33 patients with acute exacerbations of COPD (AECOPD, group A), 27 with stable COPD (group B), and 28 healthy volunteers (including 15 smokers as group C, and 15 nonsmokers as group D). MDA level in induced sputum and plasma decreased, whereas the levels of GSH, SOD and GSH-PX increased significantly in the order of groups A, B, C, and D (P<0.05). The activity of SOD in induced sputum and plasma were significantly lower in group C than in group D. No significant difference was noted in the other oxidative stress indices between groups C and D (P>0.05). The plasma levels of cortisol and ACTH showed no significant difference between the 4 groups, while the GR level in peripheral blood leukocytes increased significantly in the order of groups A, B, C and D (1565-/+719, 2069-/+488, 2739-/+926, and 4793 -/+1415 U, respectively, P<0.05). After controlling for the factor of smoking status, the plasma and sputum SOD activity were both positively correlated to GR, with the partial correlation coefficient of 0.512 and 0.564, respectively (P<0.001). Patients in different stages of COPD, especially those with AECOPD, may sustain systematic and local oxidation and anti-oxidation imbalance. Decreased SOD activity may contribute to GR level decrement in peripheral blood leukocytes in these patients.
    Nan fang yi ke da xue xue bao = Journal of Southern Medical University 06/2008; 28(6):992-6.
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    ABSTRACT: To evaluate the safety of sputum induction in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Twenty-two patients with AECOPD were enrolled in the study. All subjects inhaled a mist of 3% hypertonic saline solution and the forced expiratory volume in one second (FEV(1)) and pulse oxygen saturation (SpO(2)) were measured during the procedure. A significant fall in SpO(2) and FEV(1) was found during sputum induction by inhalation of 3% hypertonic saline solution. Mean decline in SpO(2) during sputum induction was (2.1 +/- 0.4)% (P < 0.01) and recovered within 10 min after cessation of sputum induction. Mean decline in FEV(1) during sputum induction was (12.3 +/- 3.1)% (P = 0.027), an absolute fall of (0.11 +/- 0.03) L, and the FEV(1) returned to the baseline in all subjects within 10 min after cessation of sputum induction. The sputum induction was successful in 19 of the 22 (86%) patients. The use of a standardized sputum induction protocol is relatively safe in sampling the lower airways in patients with AECOPD.
    Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 05/2005; 28(4):238-41.

Publication Stats

13 Citations
13.02 Total Impact Points

Institutions

  • 2009–2014
    • Sun Yat-Sen University
      Shengcheng, Guangdong, China
  • 2005–2012
    • Sun Yat-Sen University of Medical Sciences
      Shengcheng, Guangdong, China