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1.
Chinese Medical Journal ; (24): 804-812, 2018.
Article in English | WPRIM | ID: wpr-687035

ABSTRACT

<p><b>Background</b>Ventilator-induced lung injury (VILI) is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated. This study examined the relationship between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were ameliorated by glutamine in VILI, both in vitro and in vivo.</p><p><b>Methods</b>For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table (n = 6 in each group): control (Group C); low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence.</p><p><b>Results</b>In vivo, compared with Group C, total cell counts (t = -28.182, P < 0.01), the percentage of neutrophils (t = -28.095, P < 0.01), IL-6 (t = -28.296, P < 0.01), and TNF-α (t = -19.812, P < 0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = -6.708, P < 0.01), and the wet-to-dry ratio (t = -15.595, P < 0.01) were increased in Group H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t = 10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01), and TNF-α (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G; IL-10 in BAL fluid (t = -7.531, P < 0.01) and the expression of E-cadherin (t = -14.814, P < 0.01) and p120-catenin (t = -9.114, P < 0.01) were increased in Group H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = -21.111, P < 0.01) and TNF-α (t = -15.270, P < 0.01) were increased in the 20% cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P < 0.01) were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-α (t = 8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = -3.203, P < 0.05) and the expression of E-cadherin (t = -13.567, P < 0.01) and p120-catenin (t = -10.013, P < 0.01) were increased in the glutamine group.</p><p><b>Conclusions</b>High tidal volume mechanical ventilation and 20% cyclic stretching could cause VILI. Glutamine regulates VILI by improving cytokines and increasing the adherens junctions, protein E-cadherin and p120-catenin, to enhance the epithelial barrier function.</p>


Subject(s)
Animals , Cadherins , Metabolism , Catenins , Metabolism , Glutamine , Metabolism , Inflammation , Metabolism , Interleukin-6 , Metabolism , Lung , Metabolism , Pathology , Mice , Mice, Inbred C57BL , Ventilator-Induced Lung Injury , Allergy and Immunology , Metabolism
2.
Article in English | WPRIM | ID: wpr-636725

ABSTRACT

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous β-EP and inhibition of inflammatory mediators (5-HT and PGE2).

3.
Article in English | WPRIM | ID: wpr-351038

ABSTRACT

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P<0.05). The total dose of sufentanil was 115±6.0 μg in EAS group, significantly lower than that in control (134.3±5.9 μg) and sham (133.5±7.0 μg) groups. Similarly, the rescue dose of dezocine was the least in EAS group (P<0.05) among the three groups. Plasma β-EP levels in EAS group at T3 (176.90±45.73) and T4 (162.96±35.00 pg/mL) were significantly higher than those in control (132.33±36.75 and 128.79±41.24 pg/mL) and sham (136.56±45.80 and 129.85±36.14 pg/mL) groups, P<0.05 for all. EAS could decrease the release of PGE2. Plasma PGE2 levels in EAS group at T2 and T3 (41±5 and 40±5 pg/mL respectively) were significantly lower than those in control (64±5 and 62±7 pg/mL) and sham (66±6 and 62±6 pg/mL) groups. Plasma 5-HT levels in EAS group at T2 (133.66±40.85) and T3 (154.66±52.49 ng/mL) were significantly lower than those in control (168.33±56.94 and 225.28±82.03) and sham (164.54±47.53 and 217.74±76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and β-EP in EAS group at T3 and T4 were significantly higher than those at T1 (P<0.05); PGE2 and 5-HT levels in EAS group showed no significant difference among the different time points (P>0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous β-EP and inhibition of inflammatory mediators (5-HT and PGE2).


Subject(s)
Adult , Aged , Electroacupuncture , Methods , Esophagectomy , Female , Humans , Male , Middle Aged , Pain , Pain Management , Methods , Postoperative Complications , Therapeutics , Prospective Studies
4.
Chinese Medical Journal ; (24): 2918-2922, 2013.
Article in English | WPRIM | ID: wpr-263557

ABSTRACT

<p><b>BACKGROUND</b>p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function, but its role has not been explored in alveolar edema induced by ventilation. We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120. We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed, which resulted from the loss of p120.</p><p><b>METHODS</b>Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor). After the end of stretching for 0, 1, 2, and 4 hours, the cells were lysed, and p120 expression and c-src activation was determined by Western blotting analysis. In vivo, SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg, PEEP = 0, respiratory rate 30-40 betas/min) for 0, 1, 2, and 4 hour and some were pretreated with pp2, and alveolar edema was calculated.</p><p><b>RESULTS</b>It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells. These changes could be reversed by inhibition of c-src. We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group. Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.</p><p><b>CONCLUSIONS</b>Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema. Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).</p>


Subject(s)
Animals , Blotting, Western , Catenins , Physiology , Cells, Cultured , Mice , Pulmonary Alveoli , Pathology , Pulmonary Edema , Pathology , Rats , Rats, Sprague-Dawley , Tidal Volume , Ventilator-Induced Lung Injury , Pathology
5.
Article in Chinese | WPRIM | ID: wpr-348493

ABSTRACT

<p><b>OBJECTIVE</b>To reveal the mechanism of acupuncture at the Heart meridian in treatment of myocardial ischemia from gene level.</p><p><b>METHODS</b>A model of acute myocardial ischemia was made by ligation of left anterior descending branch of the coronary artery. Changes of gene expression pattern of the Lung meridian group, the Heart meridian group and the model group in the heart were compared.</p><p><b>RESULTS</b>Differential expression genes and expression sequence tags (ESTs) were 14 with signal log ratio > or = 1 and 20 with signal log ratio < or = -1, mainly included immunological and inflammatory reaction relative genes, cell signal transduction and transferrin relative genes, and others, in the Lung meridian group vs the model group. Differential expression genes and ESTs were 20 with signal log ratio > or = 1 and 70 with signal log ratio < or = -1, mainly included ion channel and transport protein relative genes, cell apoptosis and stress reaction protein relative genes, metabolism relative genes, cell signal transduction and transferrin relative genes, DNA's binding, transcription and transcriptional factor relative genes, immunological and inflammatory reaction relative genes, and others, in the Heart meridian group vs the model group.</p><p><b>CONCLUSION</b>In number and types of differential expression genes and ESTs with signal log ratio > or = 1 or < or = -1, the changes in the Heart meridian group vs the model group were obviously different from those in the Lung meridian group vs the model group, indicating that the Heart meridian has relative specificity in protecting against acute myocardial ischemia.</p>


Subject(s)
Acupuncture Therapy , Animals , Electroacupuncture , Heart , Meridians , Myocardial Ischemia , Therapeutics , Rats , Rats, Sprague-Dawley
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