Application and research progress of respiratory muscle training in COPD lung rehabilitation / 中国医师杂志

Chronic obstructive pulmonary disease (COPD) is a common disease with high prevalence,high mortality and high disability.A large number of studies have confirmed that lung rehabilitation is an effective treatment for patients with COPD in addition to oxygen therapy and drug therapy.Respiratory muscle training is one of the basic methods of COPD lung rehabilitation,so do a good job in COPD patients with respiratory muscle training to improve the quality of life of patients,delay the disease process is of great significance.This paper focuses on the application progress of respiratory muscle training in COPD lung rehabilitation.

Research progress of D4-GDI in the pathogenesis of lung cancer / 国际肿瘤学杂志

As one of the main members of the Rho GDI dissociation inhibitory factors,D4-GDI inhibits the dissociation of Rho protein and GDP,which is also involved in a wide range of celluar functions,such as cell contraction,adhesion,migration,proliferation and apoptosis.Recently,accumulating evidence has been suggested that D4-GDI is involved in the pathogenesis of several pulmonary diseases,such as lung cancer.Intervention of D4-GDI expression may improve the pathological changes and prognosis of these diseases.

Effect of liver depression on Th17 and treg in asthma ratsi / 国际中医中药杂志

Objective To investigate the effect of liver depression (Liver Qi Stagnation) on Th17,Treg,IL-17,IL-10 and airway inflammation in asthmatic rats,and to clarify the immune mechanism of asthma with liver depression.Methods Established the combined with disease and syndrome model of asthma with liver depression.Collected the bronchoalveolar lavage fluid (BALF) to count the total and differential cell.Lung tissue was observed in microscope; the proportion of Th17 cells and Treg cells of CD4 +T cells in peripheral blood was measured by flow cytometry; the levels of IL-17 and IL-10 were determined by ELISA.Results The total number of inflammatory cells[(96.86±4.43)× 107/L,(88.22±3.22)× 107/L],the proportion of eosinophils [(27.58 ±4.65) ％,(22.67±2.43) ％],Th17 cells[(6.86±0.98) ％,(6.01 ±0.77) ％] and IL-17 level [(48.88± 8.06)pg/ml,(43.24± 6.32) pg/ml] of asthma in liver depression group and asthma group were significantly higher than the control group [(30.58 ± 2.49) × 107/L,(0.78 ± 0.12) ％,(2.80± 0.82) ％,(24.11 ±3.40)pg/ml]; Treg cells [(3.09±0.55) ％,(3.96±0.66) ％] and IL-10 level [(19.79±2.80) pg/ml,(20.29±3.12) pg/ml] were significantly lower than the control group [(8.02± 1.26) ％,(30.79 ± 4.01) pg/ml].The total number of inflammatory cells (96.86 ±4.43) × 107/L,the proportion of eosinophils (27.58±4.65) ％ and Th17 cells(6.86±0.98) ％ and IL-17 level (48.88±8.06)pg/mL of asthma in liver depression group were significantly higher than the asthma group (88.22 ± 3.22) × 107/L,(22.67 ± 2.43) ％,(6.01 ± 0.77) ％,(43.24 ± 6.32) pg/ml;the proportion of Treg cells (3.09 ±0.55)％ was significantly lower than the asthma group (3.96± 0.66)％; and the lung histopathology symptoms was more severe than asthma group.Conclusion Liver Qi Stagnation can promote the inflammation of asthma,the imbalance of Th17/Treg and IL-17 level to aggravate the asthma.Liver depression is one of the major internal factors in recurrent episodes of asthma.

Expression of PPARγ, Nrf2 and γ-GCS-h in inflammatory cells in bronchoalveolar lavage fluid of guinea pigs with bronchial asthma / 中国病理生理杂志

AIM: To investigate the expression of PPARγ and Nrf2/γ-GCS-h in inflammatory cells in bronchoalveolar lavage fluid(BALF) of guinea pig with bronchial asthma of acute episode, and to explore the roles of PPARγ on Nrf2/γ-GCS-h expression. METHODS: Forty adult male guinea pigs were randomly divided into 4 groups (10 guinea pigs in each group): control group (group A), asthmatic group (group B), dexamethasone treatment group (group C) and rogridone treatment group (group D). The asthmatic model was established by an ovalbumin challenge method. BALF was collected, and the total cell count and the proportion of the inflammatory cells were measured. After centrifugation, the concentrations of ROS and MDA in the clear supernatant were detected. The methods of in situ hybridization and immunohistochemistry were used for detecting the expression of PPARγ and Nrf2/γ-GCS-h at mRNA and protein levels. RESULTS: The proportion of eosinophils (EOS) in BALF in group B was significantly higher than that in groups A, C and D (P<0.01). The concentrations of ROS and MDA in BALF of group B was the highest. The difference of ROS and MDA was statistically significant (all P<0.05) as compared to the control. The results of immunohistochemistry and in situ hybridization indicated that the A value was the lowest in group B as compared to that in groups A, C and D (all P<0.01). In group B, the positive correlations were observed between PPARγ and Nrf2/γ-GCS-h, between γ-GCS-h and Nrf2. A negative correlation between the proportion of EOS in BALF and the expression of PPARγ and Nrf2/γ-GCS-h was also observed (all P<0.05). CONCLUSION: In acute asthmatic models induced by ovalbumin, the expression of PPARγ and Nrf2/γ-GCS-h is decreased, and PPARγ may up-regulate the expression of Nrf2/γ-GCS-h to inhibit the inflammatory and oxidative reactions, indicating a new way for prevention and treatment of bronchial asthma.

Cigarette smoke extract regulating the expression of γ-glutamylcysteine synthetase through the pathway of PI3K/Akt-Nrf2 in the bronchial epithelial cells of rats / 中国医师杂志

Objective To observe the effect of PDK ( phosphoinositol -3-kinase, PI3K)/Akt-Nrf2 (Nuclear factor -E2 related factor) signal pathway on γ-glutamylcysteine synthetase (γ-GCS) in the bronchial epithelial cells of rats treated with cigarette smoke extract (CSE). Methods The bronchial epithelial cells were dealt with 10% concentration of CSE for different time and pretreated with PI3k inhibitor (LY294002). The expressions of Nrf2,p-Akt and γ-GCS proteins were examined by immunocytochemistry, flow cytometry, immunofluorescence and western blot. The expressions of γ-GCS mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Reduced glutathione(GSH) content and the lev-el of γ-CCS activi-ty were examined. Results GSH content in CSElh group was significantly decreased, but still higher in CSE3 and 6 groups compared to the control. Nrf2 protein mainly located in the cytoplasm. Nrf2 plasmosin mainly increased in the nucleus in control group, and Nrf2 nucleic protein significantly enhanced in CSE1, 3 and 6 groups. P-Akt protein was up-regulated at lh, reached its peak at 3h, declined slightly at 6h after exposure to CSE. The tendency of the percentage of p-Akt positive cells was as same as p-Akt protein. γ-GCS mRNA, protein and activity, gradually increased in CSE lh, CSE 3h,CSE 6h groups. Pretreated with LY294002, the expression of p-Akt protein was markedly decreases, while Nrf2 plasmosin expressed strongly, and γ-GCS mRNA, protein, activity and GSH content were significantly decreased compared to CSE3h group. Linear correlation analysis demonstrated that there were a positive correlation among Nrf2 and γ-GCS,γ-GCS activity, and among p-Akt and Nrf2,GSH,γ-GCS,γ-GCS activity. Conclusion P13K/Akt signal path might participate in Nrf2 nuclear translocation via regulating the expression of γ-GCS.

Role of PPARγ on γ-glutamylcysteine synthetase activity and expression in rats with chronic obstructive pulmonary disease / 中国病理生理杂志

AIM: To explore the effects of peroxisome proliferator-activated receptor γ (PPARγ) on the activity and expression of γ-glutamylcysteine synthetase (γ-GCS), and its role in rats with chronic obstructive pulmonary disease. METHODS: COPD model was established by the method of combining fumigation and lipopolysaccharide (LPS) intra-tracheal dripping. Meanwhile, some of the COPD rats were administered with rosiglitazone (RGZ), a PPARγ activator. The pulmonary function and the pathological changes were determined. ROS content and γ-GCS activity in lung tissues were detected. The levels of PPARγ, γ-GCS mRNA and protein expression in lung tissues were measured by immunohistochemistry, Western blotting, in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The pulmonary function (FEV_(0.3), FEV_(0.3)/FVC%, PEF) were significantly improved in RGZ group compared to COPD group. Under light microscope, lung pathological changes in COPD group conformed to pathological features of COPD. The pathological changes of lung tissue were obviously reduced in RGZ group compared to COPD group. In RGZ group, ROS content was obviously reduced and γ-GCS activity significantly increased compared to COPD group. Protein and mRNA expressions of PPARγ and γ-GCS in COPD group significantly higher than those in control group (all P<0.01), and those in RGZ group was markedly increased compared to COPD group (all P<0.05). Linear correlation analysis showed that PPARγ protein was positively correlated with γ-GCS activity (r=0.634, P<0.01), and was no significantly correlated with ROS content (r=0.214, P>0.05). PPARγ protein was positively correlated with γ-GCS protein and mRNA (r=0.553, r=0.442, all P<0.01). CONCLUSION: PPARγ activation by RGZ reduces the extent of COPD oxidant/antioxidant imbalance, which plays an important role in the prevention and treatment of COPD. In addition, PPARγ may play an important antioxidant protection role by reducing ROS production, and increasing activity and gene expression of γ-GCS in the lung.

Relationship among the concentration of plasma interleukin-10 and interleukin 13 and patients with acute exacerbated chronic obstructive pulmonary disease and its therapeutic effect-13 / 中国医师杂志

Objective To investigate the relationship among the concentration of plasma interleukin (IL)-10 and plasma IL-13 and the clinical therapeutic effect in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods Thirty-six AECOPD inpatients were enrolled in this study.Blood samples of the subjects were collected as soon as hospitalization, and plasma IL-10 and IL-13concentrations were analyzed by enzyme-linked immunosorbent assay.The clinical manifestations of subjects were quantified by a special designed score standard, and were evaluated at the time points of hospitalization, 48 hours treatment and 96 hours treatment.The therapeutic effect was evaluated by clinical manifestations score combined with pulmonary ventilation functional parameter.Eventually, the correlation among the concentration of IL-10 concentration and IL-13 and the clinical therapeutic effect were analyzed.Results The correlation coefficients between clinical manifestations score decrease and pulmonary ventilation function improvement with plasma IL-10 concentration after 48 hours treatment were 0.85 and 0.48 respectively,then, 0.64 and 0.52 after 96 hours treatment.The correlation coefficients between clinical manifestations score decrease and pulmonary ventilation function improvement with plasma IL-13 concentration after 48hours treatment were -0.41 and -0.34, after 96 hours treatment , correlation coefficients between clinical manifestations score decrease with plasma IL-13 concentration was -0.36.All of the above correlation coefficients were statistically significant.Conclusion Plasma IL-10 concentration was positively, whereas, IL-13 concentration was negatively correlated with the therapeutic effect in AECOPD patients.

Epidemic situation and risk factors analysis of COPD of residents in Changsha urban area of Hunan province / 中国医师杂志

Objective To survey the prevalence of chronic obstructive pulmonary disease (COPD)in urban areas of Hunan province and relevant risk factors and provide a basis of the prevention and treatment for COPD. Methods A questionnaire survey was conducted among 4248 residents, aged over 15, by a simple cluster random sampling method in Changsha, Hunan, Wulipai street North Station community. All the respondents filled out an unified epidemiological survey questionnaire. All of the respondents received examination for lung function. Those respondents showed FEV1/FVC ＜70% were further examined by ECG,X ray inspection for differential diagnosis. The data of epidemiological survey was analyzed by multivariate logistic regression method. Results The response rate was 92%. The total prevalence of COPD was 4. 81%.The prevalence of COPD in the males was 6. 6%, and 3. 0% in the females. The prevalence of COPD in the males was significantly higher than that in the females (x2 = 29. 915, P ＜ 0. 01). The prevalence increased with age increasing (P ＜0. 01). The more the education was, the lower the prevalence of COPD was. Risk factors analyzed with non-conditional logistic were as follow. The odd ratio (OR) for COPD in the age was 1.92(P ＜0. 01) and the odd ratio (OR) for COPD in the sex was 1.81 (P ＜0. 01). The weak lighting in house increased the risk with the OR of 4. 25(P ＜0. 01) and pet feeding further increased the risk with the OR of 12.08(P ＜0. 01). The odd ratio (OR) for COPD in the smokers was 1.74(P ＜0. 01) and the prevalence of COPD was related with smoking intensity (branch years of cigarette). Smoking intensity above 500 increased the risk of COPD. The passive smoking increased the risk with the OR of 16. 39(P ＜0. 01). The odd ratio (OR) for COPD in the paternal family history with chronic pulmonary disease was 2. 13(P ＜0. 01) and 2. 11 (P ＜ 0. 01) in the maternal family history. The odd ratio (OR)for COPD in the education degree was 0. 52(P ＜ 0. 01). Conclusions The prevalence of COPD was high in Changsha city, which might be attributed to the risk factors such as house lighting, pet feeding, cooking,aged, male, smoking, passive smoking, and family history. The education degree was the protective factor of COPD. We should intervene the relevant risk factors of COPD so that the prevalence of COPD might be cut down.

Expressions of hypoxia inducible factor-1 alpha and inducible nitric oxide synthase gene in the development of hypoxic pulmonary hypertension in rats / 中国组织工程研究

BACKGROUND:The dynamic changes of hypoxia inducible factor-1 alpha (HIF-α) and inducible nitric oxide synthase (iNOS) genes in the pulmonary artery wall during the process of hypoxic pulmonary hypertension (HPH) development need to be investigated.OBJECTIVE: This study was to observe the gene expressions of HIF-α and iNOS in the pulmonary artery wall at the different hypoxic time points, and to investigate their effects in HPH development.DESIGN: Controlled observation animal experiment.SETTING: Department of Respiration, Second Hospital Affiliated to Nanhua University.MATERIALS: Forty healthy male Wistar rats of clean grade, aged 6-8 weeks, with body mass of (220±10) g were involved in this study. They were randomized into control group (n =8) and hypoxia group (n =32). Four time points, i.e.3, 7, 14, and 21 days after hypoxia were set for the animals in the hypoxia group, 8 rats at each time point.METHODS: This study was carried out in the Institute of Oncology, Nanhua University between August 2004 and December 2005. Rats in the hypoixa group were treated according to the method reported by Li et al. Hypoxia treatment was omitted for the rats in the control group. At each time point, the rats were anesthetized, and then a micro-catheter was inserted into the right jugular vein and connected to a multichannel physiologic recorder, which was used for detecting the mean pulmonary arterial pressure (mPAP). The heart of each euthanized rat was taken out, and its right ventricle (RV), and left ventricle and septum (LV+S) were weighted. Right ventrical hypertrophy index (RVHI) reflected right ventricle hypertrophy degree. Right upper lung tissue of rat was harvested for haematoxylin & eosin (HE) staining and elastic fiber staining. Pathological image analysis software was used to determine pulmonary arterial wall area/total vascular area, lumina area/total vascular area, smooth muscle cell density in the media of pulmonary arteriole, and media thickness of pulmonary arteriole, which were used as remodeling indexes of pulmonary arteriole. HIF-1α and iNOS in the pulmonary arteriole were performed in situ hybridization and immunohistochemical detection. The mean absorbance of pulmonary arteriole wall was used as the relative content of mRNA expression and protein level.MAIN OUTCOME MEASURES: ①Changes in mPAP, RV hypertrophy degree and remodeling indexes of pulmonary arteriole of rats. ② Expressions of HIF-α and iNOS as well as their correlations with mPAP and remodeling indexes of pulmonary arteriole.RESULTS: All the 40 Wistar rats were involved in the final analysis. ①At hypoxia 7 days, mPAP was significantly higher than that of control group (P ＜ 0.05). mPAP reached to the high level at hypoxia 14 days, and then maintained at this level. ② At hypoxia 14 days, RVHI was higher than that of control group (P ＜ 0.05). ③ At hypoxia 7 days, pulmonary arteriole wall was thickened, and lumina became narrowed. There were significant differences in pulmonary arterial wall area/total vascular area, lumina area/total vascular area between hypoxia group and control group (P ＜ 0.05). At hypoxia 14 days, smooth muscle cell density in the intima-media of pulmonary arteriole, and intima-media thickness of pulmonary arteriole were significantly increased (P ＜ 0.05). At hypoxia 21 days, lumina was further narrowed, and obvious smooth muscle hyperplasy was found. HIF-1α and iNOS mRNA expression presented weak-positive in the control group; The relative content of HIF-1α mRNA did not significantly alter at hypoxia 3 and 7 days, but was obviously increased at hypoxia 14 days ,and after this, it maintained at high level. iNOS mRNA was markedly higher than that in the control group at hypoxia 3 days, reached its peak at hypoxia 7 days, was close to the level in the control group at hypoxia 14 days, and enhanced again at hypoxia 21 days, but it was still lower than that at hypoxia 3 days. ⑤HIF-α was mainly found in the intima and media, while iNOS was found in the whole layer of vessels. iNOS was weakly expressed in the intima and media of pulmonary vessels in the control group. No obvious difference in iNOS existed at hypoxia 3 days as compared with control group. iNOS was obviously expressed in media and intima at hypoxia 7 days. Vascular media was thickened at hypoxia 14 days, and the expression of iNOS was enhanced. iNOS was not found in the vascular adventitia in the control group, but was found in the vascular adventitia in the hypoxia group. ⑥mPAP was positively correlated with pulmonary vascular remodeling (r =0.976, P ＜ 0.01 ), and HIF-1α mRNA was positively correlated with iNOS protein(r =0.927, P ＜ 0.05).CONCLUSION: Both HIF-1α and iNOS exert effects in the process of HPH development of rats, and HIF-1α and iNOS gene expression may be mutually regulated.

Role of transforming growth factor-?1 inducing myofibroblast formation in hypoxic pulmonary vascular remodeling / 基础医学与临床

Objective To investigate the biological effect of transforming growth factor-?1(TGF-?1) on inducing myofibroblast formation in hypoxic pulmonary vascular remodeling.Methods Forty male Wistar rats were exposed to hypoxia for 0,3,7,14 or 21 days.Mean pulmonary arterial pressure(mPAP),vessel morphometry,right ventricle hypertrophy index(RVHI) were measured.Immunocytochemistry was used to measure the expression of ?-Smooth-muscle actin(?-SMA) and TGF-?1 in pulmonary artery walls and in situ hybridization was used to measure the expression of TGF-?1 mRNA in pulmonary artery walls.Ultrastructure alveolar wall vessels were observed by electron microscopy.Human embryonic lung fibroblasts(KMB17) phenotype after induction of hypoxiaand TGF-?1 were recorded through cell culture.Results(1) mPAP increased significantly after 7-day of hypoxia(P

Adrenomedullin relieves the pulmonary hypertension in hypoxic rats / 基础医学与临床

Objective To investigate the effects and mechanisms of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) on hypoxia pulmonary hypertension (HPH) in rats.Methods Eighteen male Wistar rats were randomly divided into three groups:control group, hypoxic group and hypoxic plus ADM group.ADM was subcutaneously administered into rats with ADM. After 21 days, The mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index[RV/(LV+S)] were measured. Hypoxic pulmonary vascular remodeling(HPSR) was observed with morphometric analysis. The level of pulmonary arterial plasma ADM was measured by radioimmunoassay. The semiquantitate in situ hybridization was used to measure the expression of ADMR mRNA in pulmonary artery walls. Results (1) The level of mPAP, RV/(LV+S),the ratio of vascular wall thick ness to external diameter(MT%) and ratio of vascular wall area to total area (MA%) were significantly higher in hypoxia group than those in control group(2) The pulmonary artery plasma ADM level was significantly higher in hypoxic group and hypoxic plus ADM group than that in control group(P

Expression and role of adrenomedullin and its receptor in patients with chronic obstructive pulmonary disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n = 12) and those with PH were placed in Group B (n = 10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted.</p><p><b>RESULTS</b>The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD (P < 0.01). In situ hybridization showed that ADM mRNA and ADMR mRNA were expressed in the pulmonary artery walls of control subjects. The expression levels were significantly higher in those of COPD sufferers (P < 0.01). Statistically positive relationships were visible between ADM and ADMR, and the plasma ADM level of Group B was significantly higher than that of Group A (P < 0.05). The plasma ADM level had a significantly positive correlation to mPAP and pulmonary vascular resistance (PVR), while being negatively correlated to levels of PaO(2).</p><p><b>CONCLUSION</b>ADM may play an extremely protective role as a local autocrine/paracrine factor in COPD.</p>

Hypoxia-inducible factor 1 alpha upregulates the expression of inducible nitric oxide synthase gene in pulmonary arteries of hyposic rat / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the expression of hypoxia-inducible factor 1 alpha (HIF-1alpha) and inducible nitric oxide synthase (iNOS) genes in rats' pulmonary arteries in different phases of hypoxia-induced pulmonary hypertension development.</p><p><b>METHODS</b>Models of chronic hypoxic pulmonary hypertension rat were duplicated by intermittent hypoxia. Mean pulmonary arterial pressure (mPAP) was measured by right-heart catheterization. HIF-1alpha and iNOS messenger ribonucleic acid (mRNA) were detected by in situ hybridization. HIF-1alpha and iNOS protein were measured by immunohistochemical analysis.</p><p><b>RESULTS</b>Expression of HIF-1alpha protein was upregulated in pulmonary arterial tunica intimae of all hypoxic rats. In pulmonary arterial tunica media, the level of HIF-1alpha protein was markedly upregulated at days 3 and 7 of hypoxia (P < 0.01), then tended to restore at 14 days and 21 days. HIF-1alpha mRNA levels in pulmonary arteries of rats began to increase significantly at day 14 of hypoxia (P < 0.01). Expression of iNOS mRNA and protein in pulmonary arteries of rats were upregulated by hypoxia for 3 days (P < 0.01), then reached its peak and maitained the same level while the extension of hypoxia. Linear correlation analysis showed that iNOS protein was associated with both mean pulmonary arterial pressure (r = 0.74, P < 0.01) and hypoxic pulmonary vascular remodeling (r = 0.78, P < 0.01), whereas the inverse was associated with HIF-1alpha protein (r = -0.52, P < 0.01).</p><p><b>CONCLUSIONS</b>HIF-1alpha and iNOS are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rat. HIF-1alpha protein may upregulate the expression of iNOS gene by transcriptional activation; in addition, iNOS protein may inhibit the expression of HIF-1alpha protein.</p>

Study on adrenomedullin synthesized in alveolar macrophages in patients with chronic obstructive pulmonary disease / 中国实用内科杂志

Objective To investigate the effects and mechanisms of adrenomedullin(ADM)synthesized in alveolar macrophages in patients with chronic obstructive pulmonary disease.Methods The bronchoalveolar lavagae fluids(BALF)were collected by bronchoscopy in 15 cases of COPD and 14 healthy cases.The expression of ADM in plasma,BALF and the culture supernatants of alveolar macrophages(AMs)were analysed by radioimmunoassay.Results (1)The cells,PMNs and AMs in BALF of COPD group were significantly higher than those of healthy group(P

aPKC and ERK regulate NRF2-?-GCS in rat lung with chronic obstructive pulmonary disease / 中国病理生理杂志

AIM: To investigate atypical protein kinase C(aPKC), extracellular signal regulated kinnase (ERK) regulating NF-E2-related factor 2 (NRF2)-?-gutamylcysteine synthetase (?-GCS) and the effect on lung of rats with chronic obstructive pulmonary disease (COPD). METHODS: The rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposure to cigarette smoke daily. The ?-GCS activity was measured. The expression of ?-GCS mRNA in lung tissue was examined by in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of p-aPKC?/?, p-ERK, NRF2 and ?-GCS in lung tissue were detected by immunohistochemistry (IH) and Western blotting, respectively. RESULTS: (1) The ?-GCS activity was higher in COPD group than that in control group. (2) The expression of ?-GCS mRNA in the COPD group was stronger than that in control group. ISH showed that the ?-GCS mRNA was expressed in alveolar epithelium and bronchiolar smooth muscle cell in the COPD group. (3) The protein expressions of p-aPKC, p-ERK, NRF2, ?-GCS were significantly higher than those in control group. IH showed that p-aPKC, p-ERK, NRF2, ?-GCS proteins were expressed in alveolar and bronchiolar epithelium in the COPD group. (4) There was a positive correlation between NRF2 and ?-GCS. ?-GCS mRNA, p-aPKC?/?, p-ERK were also positively correlated with NRF2. CONCLUSION: By upregulating the signal transduction of NRF2-?-GCS, the ERK and aPKC?/? may play an important role in the mechanism of COPD formation.

Changes of hypoxia inducible factor 1 alpha and heme oxygenase 1 in the process of hypoxic pulmonary hypertension development in rats / 中国病理生理杂志

AIM: To observe the expression of hypoxia inducible factor-1? (HIF-1?) gene and heme oxygenase-1 (HO-1) gene in pulmonary arteries in hypoxic rats. METHODS: Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary pressure (mPAP), vessel morphometry, right ventricle hypertrophy index (RVHI) were measured. Lungs were either inflation fixed for immunohistochemistry and in situ hybridization or frozen for later measurement of HO-1 enzyme activity. RESULTS: During hypoxia, mPAP increased to significantly higher values than the control values after 7-day of hypoxia,reaching its peak after 14-day of hypoxia, then remained on the high level. Pulmonary artery remodeling developed significantly after 14-day of hypoxia. Expression of HIF-1? protein in control was poorly positive, but was up-regulated in pulmonary arterial tunica intimae of all hypoxic rats. In pulmonary arterial tunica media, the levels of HIF-1? protein were markedly up-regulated after 3-day and 7-day of hypoxia, then tended to decline after 14-day and 21-day of hypoxia. HIF-1? mRNA staining was poorly positive in control, hypoxia for 3 days and hypoxia for 7 days, but began to enhance significantly after 14-day of hypoxia, then remained stable. Expression of HO-1 protein began to increase after 7-day of hypoxia, reaching its peak after 14-day of hypoxia, then remained stable. Expression of HO-1 mRNA began to increase after 3-day of hypoxia, reaching its peak after 7-day of hypoxia, then declined. CONCLUSION: HIF-1? and HO-1 are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats. Furthermore, HIF-1? may inter-regulate with HO-1 gene in this process.

Nrf2 regulates the expression of ?-glutamylcysteine synthetase in the inflammatory cells of bronchial asthma guinea pig / 中国病理生理杂志

AIM: To investigate Nrf2 that regulates the expression of ?-glutamylcysteine synthetase(?-GCS) in the inflammatory cells in bronchial asthma guinea pig bronchoalveolar lavage fluid(BALF).METHODS: Adult male guinea pigs were randomly divided into control group(group A),asthmatic group(group B) and dexamethasone group(group C).Asthmatic model was established by the method of ovalbumin challenge.MDA concentration in the lung tissue homogenate was detected.The total cell count and the proportion of inflammatory cells in BALF were measured.The methods of immunohistochemistry and in situ hybridization were used for detection of the protein and mRNA expressions of Nrf2,Bach1 and ?-GCS.RESULTS:(1) The proportion of eosinophils(EOS) in BALF and the MDA concentration of the lung tissue in group B were higher than those in group A and group C.(2) The result of in situ hybridization indicated that the A value of ?-GCS was the highest in group A compared to group B and group C,but the A value of Nrf2 and Bach1 in 3 groups has no statistical significance.(3) Immunohistochemistry indicated that the A value of ?-GCS in group B was lower than that in group A.The positive rate in cell nucleus of Nrf2 in group B was lower than that in group A and group C.The positive rate in cell nucleus of Bach1 in group B was higher than that in group A and group C.(4) The mRNA expression of ?-GCS(A value) showed positive correlation with the positive rate in cell nucleus of Nrf2 and negative correlation with the positive rate in cell nucleus.A negative correlation between the proportion of EOS in BALF of group B and the ?-GCS mRNA was observed.CONCLUSION: There is disequilibrium between oxidation and anti-oxidation in bronchial asthma guinea pig.Inflammatory reaction decreases the expression of ?-GCS in the inflammatory cells in bronchial asthma guinea pig.Dexamethasone regulates the nuclear translocation of Nrf2/Bach1 and increases the expression of ?-GCS.

Ligustrazine in the prevention of chronic hypoxic pulmonary hypertension in rat and its relationship to the gene expression of nitric oxide synthase / 中国药理学通报

A model of chronic hypoxic pulmonary hypertension (HPH) was reconstructed in rats exposed to hypoxia with normal pressure for 14 d. Chronic HPH was prevented by giving Ligustrazine (LTZ) in an intraperitoneal dose of 80 mg ?kg-1 wt. twice daily. The mean pulmonary arterial pressure (mPAP), plasma and pulmonary small arterial cGMP level, and mRNA expression of nitric oxide synthase (NOS) gene in lung tissues were studied. The results showed that the mPAP was significantly higher, but plasma and pulmonary small arterial cGMP level as well as mRNA expression of NOS gene in lung tissues were markedly lower in chronic hypoxic rats than those in control animals. LTZcould reverse those changes of above indexes in hypoxic rats, but did not affect those indexes in normal rats. There was a strong negative correlation between cGMP level and mPAP. It is suggested that the lower mRNA expression of NOS gene in hypoxic rats may be one of pathogenetic mechanisms in chronic HPH, and LTZ can increase the mRNA exprssion of NOS gene and the production of nitric oxide in hypoxic rats, which may be an important mechanism in LTZ preventing chronic HPH.

The acute inhibitory effect of adrenomedullin on hypoxia-induced pulmonary hypertension in rats / 中国病理生理杂志

AIM: The aim of this study is to investigate the acute inhibitory effects of adrenomedullin(ADM 1-52 ) on hypoxia pulmonary hypertension and its influence on systemic blood pressure. METHODS: Thirty-six male Wistar rats were divided into two groups. Eighteen were exposed to hypoxia for 21 days as hypoxic pulmonary hypertension group,and another eighteen were kept in ambient as control group. Each group were divided into three subgroups which were injected intravenously with ADM 0 1 nmol/kg, 0 3 nmol/kg, 1 nmol/kg, respectively,then hemodynamic parameters were recorded. Plasma cyclic adenosine 3,5,-monophosphate (cAMP) was measured by radioimmunoassay before,during and after injection of 0.3nmol/kg adrenomedullin(ADM 1-52 ). RESULTS: Mean pulmonary arterial pressure (mPAP)in the hypoxia and control rats treated with ADM decreased, the fall in hypoxia rats is more obviously than control( P