OBJECTIVETo determine the effects of curcumin on bleomycin (BLM)-induced pulmonary fibrosis in rats.

METHODOne hundred and forty-four male Sprague-Dawley rats were randomized into 6 groups (24 rats in each group, model group, sham group, prednisone group (0.56 mg x kg(-1) x d(-1)), curcumin with low dose 5 mg group, curcumin with middle dose group 10 mg and curcumin with high dose group 20 mg per 100 g of body weight). Rats in all groups except in sham group were injected with BLM intratracheally. Curcumin with different doses were given by gavage one time everyday for 7, 14 and 28 days. Prednisone were given to rats in prednisone group, po, serving as the positive treatment group. On the 7th, 14th, 28th day, the lung functions (inspiratory resistance, maximal volutary ventilation, forced vital capacity, Fev 0.2/FVC, peak expiratory flow) were determinated in experimental rats, respectively, and the concentrations of hydroxyproline in lung homogenates of each rat were assayed.

RESULTAdministration of curcumin in different doses improved lung functions of BLM-induced fibrotic rats in the all experimental days; and it decreased the concentration of hydroxyproline in lung homogenates compared with those levels in model control group; and it also lessened the hyperplasia of BLM-induced pulmonary fibrosis in rats.

CONCLUSIONAdministration of curcumin can suppress BLM induced pulmonary fibrosis indicated by improved respiratory function, as well as companied with low content of hydroxyproline in lung tissue of rats.

Animals ; Bleomycin ; adverse effects ; Curcumin ; pharmacology ; Hydroxyproline ; metabolism ; Lung ; drug effects ; metabolism ; pathology ; physiopathology ; Male ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; physiopathology ; Rats ; Time Factors

OBJECTIVETo investigate the effects of lipopolysaccharide (LPS) on airway inflammation, airway remodeling and the expression of Toll-like receptor 4 (TLR4) mRNA in asthmatic rats.

METHODSTwenty-four SPF level SD rats were randomly divided into four groups (n = 6): control group, low dose of LPS group, high dose of LPS group and asthma group. Using ovalbumin (OVA) to sensitize and challenge to establish asthmatic rat model. Observed pathological changes of lung tissue by HE staining, inflammatory cell infiltration was observed by airway wall eosinophils (EOS) counts; airway resistance was determined; image analysis software was used to determine the thickness of airway wall, detected airway smooth muscle TLR4 expression levels by RT-PCR.

RESULTSThe rat airway resistance and the EOS number of airway wall and the thickness of airway wall in asthma group, low dose of LPS group and high dose of LPS group were significantly higher than those in control group (P < 0.01). The above-mentioned parameters of high dose of LPS group showed significantly lower than those in asthma group and low dose of LPS group (P < 0.05). The expression of rat airway smooth muscle TLR4 mRNA in low dose of LPS group and high dose of LPS group were significantly higher than those in asthma group (P < 0.01). And the expression of rat airway smooth muscle TLR4 mRNA in high dose of LPS group was significantly higher than that in low dose of LPS group (P < 0.05).

CONCLUSIONTLR4 plays an important role in asthmatic airway inflammation and airway remodeling, LPS may play double-sided regulation in asthmatic airway inflammation and airway remodeling by activated TLR4.

Airway Remodeling ; drug effects ; Animals ; Asthma ; metabolism ; pathology ; physiopathology ; Inflammation ; metabolism ; Lipopolysaccharides ; adverse effects ; pharmacology ; Lung ; metabolism ; physiopathology ; Male ; Muscle, Smooth ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo investigate the effect of panax notoginseng saponins (PNS) injection on pulmonary artery pressure and the expression of p38MAPK in lung tissue of rats subjected to chronic hypoxia.

METHODSThirty adult male Sprague Dawley rats were randomly divided into three groups (ten in each group): rats in control group were exposed to normoxic condition and the rats in hypoxia group and PNS group were subjected to 4-week hypoxia, and PNS injection (50 mg · kg(-1) · d(-1)) was administrated intraperitoneally at 30 min in the PNS group daily before the rats were kept in the hypoxic chamber, while rats in the other two groups received equal dose of normal saline instead. After chronic hypoxia, mean pulmonary artery pressure (mPAP) and mean carotid artery pressure (mCAP) were measured. The heart and lung tissues were harvested, and right ventricle (RV) and left ventricle plus ventricular septum (LV+S) were weighed to calculate the ratio of RV/(LV+S). The expression of p38MAPK mRNA was determined by reverse transcription-polymerase chain reaction, the quantity of phosphorylated p38MAPK (p-p38MAPK) in rat lung tissues and pulmonary arterioles was determined by Western blot and immunohistochemistry.

RESULTSCompared with the control group, mPAP and the ratio of RV/(LV+S) in the hypoxia group were increased, the expression of p-p38MAPK in pulmonary arterioles and p38MAPK mRNA in the lung were higher (P<0.05). The changes of these parameters in the hypoxia group were significantly attenuated by PNS treatment (P<0.05).

CONCLUSIONPNS injection was shown to prevent hypoxic pulmonary hypertension at least partly by regulating p38MAPK pathway.

Animals ; Arterioles ; drug effects ; metabolism ; Blood Pressure ; drug effects ; Blotting, Western ; Carotid Arteries ; drug effects ; physiopathology ; Disease Models, Animal ; Heart Ventricles ; drug effects ; physiopathology ; Hemodynamics ; drug effects ; Hypertension, Pulmonary ; complications ; enzymology ; physiopathology ; Hypoxia ; complications ; enzymology ; physiopathology ; Injections ; Lung ; drug effects ; enzymology ; pathology ; physiopathology ; MAP Kinase Signaling System ; drug effects ; Male ; Panax notoginseng ; chemistry ; Pulmonary Artery ; drug effects ; physiopathology ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley ; Saponins ; administration & dosage ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

OBJECTIVETo study the effect of hydrogen-rich saline on blood pressure and antioxidant ability of lung tissue in scalded rats following delayed resuscitation.

METHODSThe hydrogen-rich saline was prepared (hydrogen-saturated normal saline with hydrogen concentration of 0.6 mmol/L). Twenty SD rats were divided into hydrogen-rich saline group (HS) and normal saline group (NS) according to the random number table, with 10 rats in each group. All the rats were subjected to 30% total body surface area (TBSA) full-thickness scald. Rats in HS and NS groups were infused with hydrogen-rich saline or normal saline with one half of the total fluid replacement volume as calculated according to the Parkland formula (4 mL×kg(-1)×%TBSA(-1)) at post scald hour (PSH) 7 and one-quarter of the volume at PSH 9 and 17 respectively. The general condition of rats during the experiment was observed. The systolic pressure of rats was measured at PSH 6 and 24. All rats were sacrificed at PSH 24 to collect lung tissue for detecting superoxide dismutase (SOD) inhibition ratio and malondialdehyde (MDA) level. Data were processed with t test.

RESULTSAll rats survived through the experiment. The systolic pressure of rats in HS group and NS group was respectively (87 ± 4) mm Hg (1 mm Hg = 0.133 kPa) and (86 ± 5) mm Hg at PSH 6, and the values were close (t = 0.213, P = 0.834); however the systolic pressure at 24 h was higher in HS group than in NS group [(124 ± 7) mm Hg vs. (115 ± 6) mm Hg, t = 2.958, P = 0.008]. SOD inhibition ratio of lung tissue in HS group [(0.465 ± 0.014)%] was higher than that in NS group [(0.358 ± 0.021)%, t = 11.767, P = 0.000]. MDA level of lung tissue in HS group [(922 ± 196) pmol/mg] was lower than that in NS group [(1118 ± 212) pmol/mg, t = -2.142, P = 0.046].

CONCLUSIONSDelayed resuscitation for scalded rats with hydrogen-rich saline is helpful in the recovery of systolic pressure, and it can ameliorate lung tissue injury caused by reperfusion through enhancing the effect of antioxidase.

Animals ; Antioxidants ; metabolism ; Blood Pressure ; Burns ; metabolism ; physiopathology ; Disease Models, Animal ; Hydrogen ; pharmacology ; Lung ; drug effects ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Resuscitation ; Sodium Chloride ; pharmacology

AIM: In an effort to identify novel, small molecules which can affect the proliferation of lung cancer cells, F-01A, a polyether antibiotic isolated from the fermentation broth of Streptomyces was tested. METHOD: F-01A was tested for its antitumor properties on the lung cancer cell line SPC-A-1, at six doses (0.1, 0.5, 1, 2.5, and 5 μmol·L(-1)), using various cellular assays. Cell viability was measured by the MTT assay, Hochest 33258 was used to study nuclear morphology; DNA ladder and the loss of mitochondrial membrane potential were also evaluated. RESULTS: F-01A induces apoptosis against SPC-A-1 cells in a dose-dependent manner. The IC50 is 0.65 μmol·L(-1), and the inhibition at 5 μmol·L(-1) is 87.89%. Further, JC-1 staining indicates F-01A could induce the loss of mitochondrial membrane potential, and the DNA fragment is evident. CONCLUSION Mechanistic analysis showed that F-01A induced apoptosis of cancer cells probably in the mitochondrial pathway. The antitumor actions of F-01A involve activation of the apoptotic pathway against SPC-A-1 cells, and it may be valuable for further drug development.
Anti-Bacterial Agents ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Growth Inhibitors ; pharmacology ; Humans ; Lung Neoplasms ; physiopathology ; Membrane Potential, Mitochondrial ; drug effects ; Streptomyces ; chemistry ; metabolism

To explore the dose-effect relationship between vitamin C and paraquat (PQ) poisoning rats.
 Methods: A total of 40 Sprague-Dawley (SD) rats were randomly divided into 4 groups: a control group, a PQ poisoning group, a vitamin C group 1 and a vitamin C group 2 (n=10 in each group). 150 mg/kg PQ was perfused into rat stomach to establish PQ poisoning rat model. In PQ poisoning group, 30 mg/kg methylprednisolone and 2.5 mg/kg cyclophosphamide were injected peritoneally on the basis of PQ poisoning rat model. In vitamin C1 and C2 group, vitamin C was injected at a dosage of 5 or 500 mg/kg, respectively. The control group only received normal saline (NS). The malondialdehyde (MDA), liver and kidney function as well as arterial blood gas in the blood were examined 36 h later. At the end, the rats were killed and took the liver tissues for pathological examination and weight ratio calculation. The glutathione peroxidase (GSH-PX), ctychrome C (Cyt C) in the liver tissues were detected by chromatometry, and the Bcl-2 was detected by Western blot.
 Results: Compared with the PQ poisoning group, the MDA and Cyt C were decreased, the GSH-PX was increased, and liver and kidney functions were improved in the vitamin C group 1 (all P<0.01); but in the vitamin C group 2, the MDA increased and liver/kidney functions were impaired (all P<0.01). The expression of Bcl-2 in the PQ poisoning group was lower than that in the control group; compared with the PQ poisoning group, it was increased in the vitamin C1 group, while it was decreased in the vitamin C group 2 (both P<0.01). There was no obvious difference in the lung function, wet/dry weight ratio and pathological changes between the poisoning group and experimental groups (all P>0.05).
 Conclusion: Vitamin C at the low dose shows a certain degree of protection for the liver and kidney in the PQ poisoning rats model through it antioxidative activity and anit-apoptosis activity, while vitamin C at the high does may promote oxidation. Meanwhile, vitamin C doesn't show protective effect on lung in the PQ poisoning rats.
Animals ; Apoptosis ; drug effects ; Ascorbic Acid ; administration & dosage ; pharmacology ; Cytochromes c ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Glutathione Peroxidase ; drug effects ; Kidney ; drug effects ; pathology ; physiopathology ; Lung ; drug effects ; pathology ; physiopathology ; Malondialdehyde ; metabolism ; Paraquat ; toxicity ; Protective Agents ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vitamins

BACKGROUNDWith the widespread use of ventilators in treating critically ill patients, the morbidity of ventilator-induced lung injury (VILI) is increasing accordingly. VILI is characterized by a considerable increase in microvascular leakiness and activation of inflammatory processes. In this study we investigated the effects of inflammatory mediators in VILI rat serum on endothelial cytoskeleton and monolayer cellular permeability, as well as the therapeutic effect of ulinastatin, to explore the pathogenesis and the relationship between biotrauma and lung oedema induced by VILI.

METHODSThirty healthy male Sprague-Dawley rats were randomly divided into three groups: group A (normal tidal volume ventilation), group B (high tidal volume ventilation) and group C (high tidal volume ventilation plus ulinastatin). The serum of each rat after ventilation was added to endothelial cell line ECV-304 medium for two hours to observe the effects of serum and/or ulinastatin on endothelial fibrous actin and permeability.

RESULTSCompared to rats ventilated with normal tidal volume, serum of rats ventilated with high tidal volume caused a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity at the peripheral filament bands and formation of the long and thick stress fibres in the centre resulting in endothelial contraction and higher permeability. Prior treatment with ulinastatin lessened the above changes significantly. The changes of permeability coefficient of endothelial permeability after group A, B or C rats serum stimulation were (6.95 +/- 1.66)%, (27.50 +/- 7.77)% and (17.71 +/- 4.66)% respectively with statistically significant differences (P < 0.05) among the three groups.

CONCLUSIONSThe proinflammatory mediators in the serum of the rats given high tidal volume ventilation increases endothelial permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin lessens the permeability by inhibiting of proinflammatory mediators.

Actins ; analysis ; metabolism ; Animals ; Anti-Inflammatory Agents ; therapeutic use ; Cell Membrane Permeability ; drug effects ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; physiology ; Glycoproteins ; therapeutic use ; Humans ; Lung ; drug effects ; metabolism ; Lung Diseases ; etiology ; physiopathology ; prevention & control ; Lung Injury ; Male ; Microscopy, Fluorescence ; methods ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiration, Artificial ; adverse effects ; Tidal Volume ; drug effects ; Ventilators, Mechanical ; adverse effects

OBJECTIVETo investigate the effect of arginine vasopressin (AVP) on alveolar fluid clearance (AFC) in acute lung injury (ALI).

METHODSForty-eight healthy adult Sprague-Dawley rats were randomly divided into control group, ALI model group and AVP treatment group. The pathological changes in the lungs, lung water content, alveolar permeability and AFC were observed, and the expressions of alveolar epithelial sodium channel (ENaC) and Na⁺, K⁺-ATPase were measured.

RESULTSCompared with those in the model group, the rats treated with AVP showed significantly decreased alveolar permeability (0.27 ± 0.15 vs 0.59 ± 0.19) and lung water content (5.01 ± 1.59 vs 8.67 ± 1.79) (P<0.05) and increased AFC (23.56 ± 4.51 vs 8.28 ± 3.57) and of α-ENaC expressions (1.296 ± 0.322 vs 0.349 ± 0.141) and α1-Na⁺, K⁺-ATPase (1.421 ± 0.389 vs 0.338 ± 0.186) (P<0.05).

CONCLUSIONAVP can promote AFC in with ALI possibly by up-regulation of α-ENaC, α1-Na⁺, and K⁺-ATPase.

Acute Lung Injury ; drug therapy ; Animals ; Arginine Vasopressin ; pharmacology ; Epithelial Sodium Channels ; metabolism ; Lung ; drug effects ; pathology ; Pulmonary Alveoli ; drug effects ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVETo investigate the molecular mechanism of platycodin D showing the inhibitory effect on proliferation and induced apoptosis of humane long cancer cells A549.

METHODHumane long cancer cells A549 were cultured in vitro, with the final PD concentration of 5-20 micromol x L(-1). PD's inhibitory effect on cell proliferation was examined by MTT assay. Morphological changes in cells were observed with microscope. The cell apoptosis rate was detected by Annexin V-FITC/PI double staining. The change of mitochondrial membrane potential was detected by JC-1. The protein expressing of leaved Caspase-3, cleaved Caspase-9, cleaved PARP, Bcl-2, Bcl-xl, Bak and Bax were detected by Western blot analysis.

RESULTPD could inhibit the proliferation of A549 cells and show stronger effect with the increase of concentration and over time. Compared with the control group, PDs of different concentration showed significant increase in the cell apoptosis rate, decrease in mitochondrial membrane potential after 24 h. Protein electrophoresis inspection showed cut segments in both protein Caspase-3 and Caspase-9 and notable fractures with time. Further study found that PD decreased Bcl-2, Bcl-xl proteins and increased Bax, Bak proteins after processing A549 cells.

CONCLUSIONPD shows notable effect on cytotoxicity and can induce A549 cell apoptosis. It causes decrease in mitochondrial membrane potential by regulating Bax, Bak, Bcl-2 and Bcl-xl expressions, and thus activating caspase and finally causing long cancer cell apoptosis.

Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Saponins ; pharmacology ; Triterpenes ; pharmacology

BACKGROUNDTreatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia.

METHODSThirty-two male Sprague-Dawley rats were randomly assigned to four groups: vehicle + saline group, melatonin + saline group, vehicle + lipopolysaccharide group, melatonin + lipopolysaccharide group. The rats were treated with melatonin (10 mg/kg, intraperitoneal injection (i.p.)) or vehicle (1% ethanol saline), 30 minutes prior to lipopolysaccharide administration (6 mg/kg, intravenous injection). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios (W/D), myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B (NF-kappaB) p65 was evaluated by Western blotting.

RESULTSPaO(2) in the vehicle + lipopolysaccharide group decreased compared with that in the vehicle + saline group. This decrease was significantly reduced in the melatonin + lipopolysaccharide group. The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin + lipopolysaccharide group. The W/D ratio increased significantly in the vehicle + lipopolysaccharide group (6.1 +/- 0.18) as compared with that in the vehicle + saline group (3.61 +/- 0.3) (P < 0.01), which was significantly reduced in the melatonin + lipopolysaccharide group (4.8 +/- 0.25) (P < 0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle + lipopolysaccharide group compared with that in the vehicle + saline group, which was reduced in the melatonin + lipopolysaccharide group. The TNF-alpha level of pulmonary tissue increased significantly in the vehicle + lipopolysaccharide group ((8.7 +/- 0.91) pg/mg protein) compared with that in the vehicle + saline group ((4.3 +/- 0.62) pg/mg protein, P < 0.01). However, the increase of TNF-alpha level of pulmonary tissue was significantly reduced in the melatonin + lipopolysaccharide group ((5.9 +/- 0.56) pg/mg protein, P < 0.01). Pulmonary IL-10 levels were elevated markedly in the vehicle + lipopolysaccharide group in contrast to that in the vehicle + saline group, whereas the elevation was augmented in the melatonin + lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle + lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin + lipopolysaccharide group.

CONCLUSIONMelatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-kappaB activation.

Acute Lung Injury ; drug therapy ; pathology ; Animals ; Blotting, Western ; Endotoxemia ; drug therapy ; physiopathology ; Interleukin-10 ; metabolism ; Lipopolysaccharides ; toxicity ; Lung ; drug effects ; metabolism ; Male ; Melatonin ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism