AIM: To observe the effect of aminoguanidine (AG) on hemodynamics and lung capillary permeability in acute lung injury (ALI) in rabbits. METHODS: 24 rabbits were equally divided into four groups: saline group, endotoxin group, AG group and AG plus endotoxin group. In AG plus endotoxin group, endotoxin was injected to animals to make an ALI model, 25mg/kg AG was injected following that and let this sustain 3 hours. Meanwhile, mean arterial pressure (MAP), mean pulmonary arterial pressures (MPAP) and blood gas analyses were observed during this period. At the end of the experiment, broncho-alveolus lavage was performed, pathologic samples were treated routinely and lung wet weight/dry weight ratio was calculated. RESULTS: After endotoxin injection, MAP and arterial oxygen pressure (PaO 2) decreased, and MPAP increased significantly. The injection of AG had little effect on MAP, but AG could markedly decrease MPAP and increase PaO 2. Cell count in broncho-alveolus lavage fluid (BALF) was less in AG plus endotoxin group than in endotoxin group. Although AG did not affect total protein in BALF, low molecular weight proteins decreased in AG plus endotoxin group by the assay of electrophoresis. Tissue wet weight/dry weight ratio also decreased in this group. Pathologic study showed that there were fewer inflammatory cells and less lung edema in AG plus endotoxin group. CONCLUSION: AG could improve hemodynamics status and attenuate acute lung injury induced by endotoxin in rabbits. [

Objective To investigate possible intracellular s ignal molecules involved in TGF-?-induced airway smooth muscle cell proli feration in rats. Methods The cultured airway smooth muscle cells were divide d into 3 groups: control group (20 mL?L -1FCS/DMEM), 10 ?g?L -1 TGF-?1 group and 10?g?L -1 TGF-?1 /U-0126 (1 ? mol?L -1) group. The proliferation of ASMCs was detected by MTT. Exp ression of phospho-p42/p44 extracellular signal-regulated kinase (ERKs) with i mmunocytochemistry were examined in different groups. A values were detected by image analysis. Results By MTT, A values of 10?g?L -1 TGF- ?1 group (0.36?0.043) were significantly higher than those of control grou p (0.126?0.052, t=5.44,7.62, P

Objective To investigate the therapeutic effect of fluvastatin in bleomycin-induced pulmonary fibrosis in rats. Methods Pulmonary fibrosis was induced in SD rats by intratracheal instillation of bleomycin A_ 5 . The rats were than divided randomly into three groups: the rats in the first group received daily fluvastatin 20mg/kg (group Flu),those of the second group received normal saline (group BLM) orally only,and those of controls (group N) received normal saline both intratracheally and orally. Five rats in each group were sacrificed 1,3,7,14 and 28 days after intratracheal instillation of bleomycin. Pathological changes in the lungs were evaluated by HE stain and Masson′s trichrome stain. Collagen content of the lung tissue was assessed by hydroxyproline concentration. Alveolar macrophages,polymorphonuclear leukocytes and lymphocytes in bronchoalveolar lavage fluid (BALF) were counted. Hyaluronic acid (HA) and laminin (LN) in BALF were determined by radioimmunoassay. Results The degree of alveolitis and pulmonary fibrosis in group Flu was improved as compared with that of group BLM. Hydroxyproline concentrations of group Flu were significantly lower than that of group BLM 7 days after bleomycin A_ 5 instillation. Total cell counts and percentage of polymorphonuclear leukocytes and lymphocytes in BALF were significantly reduced in group Flu. HA and LN levels in BALF were also lower in group Flu compared with group BLM. Conclusion Fluvastatin could alleviate bleomycin-induced pulmonary fibrosis in rats.

Objective To evaluate the ability of goblet cell in the airway in rat with asthma to synthesize granulocyte-macrophage colony-stimulating factor (GM-CSF),and the role of calcium-activated chloride channel (CLCA) in the synthesis. Methods A model of asthma was replicated in male BALB/c mice with ovalbumin sensitization. The goblet cells in small bronchi were identified with AB-PAS staining,and the expression of GM-CSF in the same airway was assessed with immunohistochemistry staining. The recombinant plasmid of pIRES2-EFGP/hCLCA1 was transfected stably into the human mucoepidermoid cell NCI-H292. The expression and transcription levels of GM-CSF in transfected cells were determined with immunohistochemistry staining and RT-PCR assay. The non-transfected cell and the transfected cell exposed to niflumic acid (NFA),which was a CLCA inhibitor,were designated as two control groups. Results Positive staining of GM-CSF expression could be seen in the goblet cells of small bronchi. The cells with expression of hCLCA1 showed much higher levels of GM-CSF expression and transcription than those of two control groups. It was also found that NFA could effectively reduce the levels of GM-CSF in transfected cells. Conclusion The goblet cell of asthmatic airway can synthesize GM-CSF,and one of mechanisms is the increased expression of CLCA.

Objective To study the mechanism of apoptosis inducing and anti-invasive effects of curcumin on human lung adenocarcinoma cell (A549). Methods MTT colorimetry method, fluorescence mieroscopy, and FCM combining with PI and AnnexinV-FITC double pigmentation method were used to study the growth and apoptosis of A549 cells after being treated with curcumin, and Western blotting was used to identify apoptosis-inducing and anti-invasive effects. Results Under the effect of the curcumin, the nucleoli of A549 cells were found to be fragmented into different sized apoptosis bodies under fluorescence microscopy, and cell proliferation was obviously suppressed under the effect of curcumin in different concentrations, with the IC 50 value of 18?mol/L. When the curcumin concentration was increased from 5?mol/L to 40?mol/L, Annexin-FITC single positive cells (early apoptosis cell) were increased from 3.4% to 65.9%, and the proliferation of cells was blocked at G 2 phase. When curcumin concentration was increased from 10?mol/L to 20?mol/L curcumin effects 30 minutes, the expression of PARP in A549 cells was increased after 30 minutes. Curcumin could also down-regulate MMP-2 and up-regulate TIMP-2 expression. Conclusions Curcumin can interfere with cell growth cycle of A549 cells and suppress cell growth, which is concentration dependent. The anti- invasive effects of curcumin is probably the result of down-regulation of MMP-2 and up-regulation of TIMP-2 expression.

AIM: To examine whether calcitonin gene-related peptide (CGRP) enhances nitric oxide (NO) level in pulmonary circulation blood and observe the influence of CGRP on mean pulmonary artery pressure (mPAP) in rabbits with acute lung injury (ALI) caused by oleic acid. METHODS: The level of NO was assessed by measuring the presence of nitrite in cervical artery blood by the Griess reaction, mPAP was measured with right ventricular catheter. RESULTS: The level of nitrite in cervical artery blood was significantly increased and the mPAP was markedly reduced after administration of CGRP intravenousely.CONCLUSION: CGRP enhanced the NO level of pulmonary circulation blood and reduces the mPAP significantly in rabbits with ALI.

Objective:To observe the inhibitory effect of fluvastatin (Flu) on the proliferation of the rat lung fibroblasts cultured in vitro . Methods: Normal rat lung derived fibroblasts were cultured in media containing Flu. The influences of Flu on the growth curve of the fibroblasts were observed by cell count and MTT colorimetry. The inhibition effect of Flu serial dilutions on the fibroblasts proliferation was investigated. Influence of Flu on division index of the fibroblasts was analyzed by direct cell count. Chemical colorimetry was used to detect the hydroxyproline in the media. Results: Flu inhibited the proliferation of the normal rat lung fibroblasts in the manner of dose dependence( P

Objective To observe the effect of ulinastatin on tumor necrosis factor(TNF-α)and interleukin-6(IL-6)in radiation-induced lung injury.Methods Severity-two female SD rats were randomly divided into 3 groups as control group,irradiation group and treatment group(administered with Ulinastatin).Rats in irradiation group and treatment group were irradiated with linear accelerator at a single dose of 25 Gy.After irradiation rats in treatment group were injected daily with ulinastatin at a dose of 100000 U-kg-1·d-1 for 7 days through caudal vein while rats in control group and irradiation group were injected with the same volume of saline.Rats were killed at 2 h,4,8 and 24 weeks.Samples of lung tissues were observed by using HE staining.Expression of TNF-α in lung was determined by Western blot and expression of IL-6 in serum was determined by ELISA.Data were analyzed by SPSS software.Results Expressions of TNF-α in lung and IL-6 in serum increased significantly after irradiated in irradiation group compared with control group,and it reached the peak at 4 weeks(q=5.63、6.21,P＜0.01).Though expressions of TNF-α and IL-6 in ffeatment group also increased compared with control group,the difference between irradiation group and treatment group was statistic significantly(q=4.97、7.42,P＜0.01).Conclusions TNF-α and IL-6 play an important role in radiation-induced lung injury.Ulinastatin could suppress the inflammatory response and radiation-induced lung injury effectively by decreasing the levels of TNF-α and IL-6.

AIM: To investigate the relationship between inflammatory cell infiltration and proto-oncogenes expression in asthma. METHODS: Guinea pigs were used as asthma models challenged by ovoglobulin. Dot-blot, Northern-blot and immunochemical techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Inflammatory cell infiltration was showed by pathologic study.RESULTS: c-fos and c-myc mRNA could not be detected or expressed at very low level in control group. Those were greatly increased after the animals are challenged by ovoglobulin. Immunochemical study showed that Fos, Myc, Jun and Sis expressed at low level in control group, and those were increased after the challenge. There was little inflammatory cell infiltration in control group. Lymphocyte, neutrophil and eosinophil were detected immediately after the challenge, a great number of inflammation cells could be seen after 12-24 h of the challenge. Majority of neutrophil and eosinophil were under mucosa or in epithelium in airway. CONCLUSION: Oncogenes expression had strong relationship with airway inflammation.

AIM: To observe the preventive effect of DNA vaccine based on human calcium-activated chloride channel 1 (hCLCA1) on airway hyperresponsiveness in asthmatic mice.METHODS: The DNA vaccine was constructed by inserting the hCLCA1 gene into pSecTag-2A, and then BALB/c mice were vaccinated by im. once every two weeks. Serum antibody was checked with the antigen of mCLCA3 by ELISA analysis. Asthma was induced with ovalbumin in the vaccinated mice. The airway pressure time index (APTI), the contractile responsiveness of isolated tracheal rings and the number of eosinophil in bronchoalveolar lavage (BAL) were investigated. Mice injected with pSecTag-2A, saline or normal mice were regarded as control groups. RESULTS: The title of antiserum binding to mCLCA3 in vaccine group was 1∶800 to 1∶(1 000) after three times vaccination. Compared with normal group, APTI, contractile responsiveness and number of eosinophil in vaccine group, pSecTag-2A or saline group were increased markedly (P