Activation of lung endothelial cells by extracellular histone in mice with acute respiratory distress syndrome / 中华劳动卫生职业病杂志

Objective@#To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) .@*Methods@#The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model.@*Results@#The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells.@*Conclusion@#Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.

The comparison of heparan sulfate and its fragments on the protection against extracellular histones during the pathogenesis of acute respiratory distress syndrome / 中华劳动卫生职业病杂志

Objective@#In order to explore the role of heparan sulfate (HS) during the pathogenesis of acute respiratory distress syndrome (ARDS) , the protective effect of HS and its fragments against extracellular histones was compared.@*Methods@#Calf thymus histones (CTH) were injected via femoral vein to induce ARDS in rats. HS, HS fragments or saline was intraperitoneally injected (10mg/kg, Q6h, 24h) to test the protective effect against CTH. The ratio of wet/dry lung weight, protein content in bronchoalveolar lavage fluid (BALF) , total leukocyte and neutrophil count in BALF were measured.@*Results@#After CTH injection, the ratio of wet/dry lung weight (5.7±0.95) was much higher than the saline control group (3.1±0.15). The protein content (0.47±0.086mg/ml) , total leukocyte[ (97.4±15.6l) ×104/ml] and neutrophil (18±3.4/LPF) in BALF were obviously increased compared with the saline control group. The intervention of HS evidently decreased ratio of wet/dry lung weight (4.2±0.41) , protein content[ (0.26±0.019) mg/ml], leukocyte[ (61.3±5.74) ×104/ml] and neutrophil (12±1.8/LPF) in BALF. HS fragments also decreased ratio of wet/dry lung weight, protein content, leukocyte and neutrophil count in BALF though the strength was much less than HS.@*Conclusion@#HS and its fragments could provide protection against extracellular histones during the pathogenesis of ARDS. For the protective effect full length HS was much better than HS fragments.

The clinical study on the correlation of lysophosphatidic acid and vascular endotheli growth factor and endothelin in serum of pneumoconiosis / 中华劳动卫生职业病杂志

Objective@#To explore the role of lysophosphatidic acid, vascular endothelial growth facor and endothelin in the pathogenesis of pulmonary fibrosis in coal workers’pneumoconiosis patients, the relationship of lysophosphatidic acid, VEGF and ET in serum was studied.@*Methods@#Sixty two pneumoconiosis patients were selected as cases group, which included 23 cases of stage Ⅰ, 25 cases of stageⅡand 14 cases of stageⅢ. Twenty workers were selected as dust exposure group who exposed to coal dust for more than 2 years and had not been diagnosed as pneumoconiosis. Ten healthy people who had no occupational dust exposure were simultaneously selected as the control group. The serum levels of LPA, VEGF and ET were measured by ELISA.@*Results@#The serum levels of VEGF and ET in coal dust exposed group and pneumoconiosis group were much higher than in the control group. The differences were statistically significant among the three groups (P<0.01) . The serum levels of LPA increased in the dust exposed group, stage Ⅰand stage Ⅱgroup. The serum levels of LPA correlated positively with the levels of VEGF and ET (P<0.05) .@*Conclusions@#The serum levels of LPA, VEGF and ET had evident correlation with the pulmonary fibrosis caused by coal dust, which indicate that LPA, VEGF and ET may play a pivotal role in the process of pulmonary fibrosis. The study will throw light on both pathogenesis and early intervention for pneumoconiosis.

The study on the change of extracellular histones in human plasma during the pathogenesis of silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the plasma level of extracellular histones in patients with silicosis, and to explore the role of extracellular histones in the pathogenesis of pulmonary fibrosis in silicosis.</p><p><b>METHODS</b>Sixty-two patients with silicosis were enrolled as the silicosis group, consisting of 23 patients with stage I silicosis, 25 with stage II silicosis, and 14 with stage III silicosis; sixty workers who had a history of occupational exposure to silica dust for more than 2 years and had not been diagnosed with silicosis were enrolled as the silica dust exposure group; sixty-five healthy workers without a history of occupational exposure to dust were enrolled as healthy controls. Enzyme-linked immunosorbent assay was applied to measure the plasma levels of plasma extracellular histone (H4) and transforming growth factor-β(TGF-β).</p><p><b>RESULTS</b>Compared with healthy controls [(0.82±0.67) μg/ml], the silica dust exposure group[(4.14±2.85) μg/ml] and silicosis group[(9.50±5.04) μg/ml] had significant increases in plasma level of H4 (P<0.01). The plasma level of H4 was significantly correlated with the stage of silicosis(r=0.8955, P=0.0388). The silicosis group had a significantly higher plasma level of TGF-β than the silica dust exposure group and healthy controls(P <0.05). In the patients with silicosis, the plasma level of H4 was significantly correlated with that of TGF-β(r=0.5375, P<0.01).</p><p><b>CONCLUSION</b>The plasma level of extracellular histones increases significantly in the pathogenesis of silicosis, and extracellular histones may play an important role in the progression of fibrosis in silicosis.</p>

The protective effect of chlorophyllin against oxidative damage and its mechanism / 中华内科杂志

Objective To investigate whether chlorophyllin could protect human umbilical vein endothelial cell (HUVEC) against oxidative damage by inducing the expression of heme oxygenase-1 (HO-1) and to explore the underlying mechanism.Methods The cellular protection of chlorophyllin against oxidative damage was detected by cell-survival assay with flow cytometry.The level of free radicals was detected directly by electron spin resonance spectra.The induced expression of HO-1 was shown by RT-PCR,Western blot,immunofluorescence confocal laser microscopy and enzymatic activity test.Whether the activation of PI3K/Akt pathway was involved was detected by Western blot.Results Chlorophyllin could protect HUVEC against oxidative damage caused by H2O2 via scavenging the excessive free radicals.Chlorophyllin treatment could induce expression of HO-1 in a dose- and time-dependent manner.The activation of PI3K/Akt pathway was required in the induction of HO-1.LY294002,the specific inhibitor of PI3K,could suppress the activation of PI3K/Akt and the induced expression of HO-1 in a dose-dependent manner.Conclusions Chlorophyllin shows cellular protection against oxidative damage by counteracting the excessive free radicals.Up-regulation of HO-1 expression plays a pivotal role in the protection of chlorophyllin,while the activation of PI3K/Akt signaling pathway is required in the induction of HO-1.

Clinical analysis of risk factors of acute kidney injury in patients with chronic kidney disease / 中国医师进修杂志

Objective To evaluate the risk factors of patients with acute kidney injury (AKI) in patients with chronic kidney disease (CKD) for the early detection and early treatment of CKD.Methods One hundred and twenty-seven CKD patients were divided into groups according to AKI existing, 60 cases with out AKI (CKD group), 67 cases with AKI (A/C group) and then A/C group patients were divided into non-older age group (35 cases, ＜60 years old) and older age group (32 cases, ≥60 years old).The protopathy, causative factors and so on were analyzed.Results There was different causative factors in different age group.Logistic regression model indicated that the major risk flactors of AKI in CKD were severe infection (OR = 5.236),hypovolemia (OR = 5.083 ),heart failure (OR = 8.283) and using renal toxicity medicine (OR = 5.246),P ＜ 0.05.Conclusion The major risk factors of AKI in CKD patients include severe infection, hypovolemia, heart failure and renal toxicity medicine.

Protective effect of heme oxygenase-1 and its reaction product,carbon monoxide on acute liver injury induced by carbon tetrachloride in rats / 北京大学学报(医学版)

Objective:To investigate the protective role of heme oxygenase-1 and its reaction product,carbon monoxide against acute liver injury induced by carbon tetrachloride in rats.Methods: Thirty male Sprague-Dawley rats were randomly divided into six groups with five in each.The control group received a single dose of corn oil injection.Carbon tetrachloride was injected intraperitoneally(i.p) to establish acute liver injury models in rats.Hemin(50 ?mol/kg) was administered i.p.12 hours before CCl_4 treatment,with an aim to induce HO-1 protein expression in the liver of rats.Carbon monoxide was injected i.p.12 hours prior to CCl_4 injection,resulting in about 8%-12% carboxyhemoglobin concentration in vivo.The expression of HO-1 in the liver of hemin-treated rats was determined by western blot method at different time points.At 24 h after carbon tetrachloride administration,all rats were sacrificed to collect blood samples for the examination of ALT,AST levels and to remove liver tissues for analysis of MDA concentration,SOD activity and caspase-3 activity as well as TNF-a contents.In addition,histopathological changes were investigated and hepatocyte apoptosis was detected by TUNEL method.Results: The administration of carbon tetrachloride to rats caused a marked hepatic damage,characterized by significant elevation of serum ALT,AST levels(2 136.3?163.4 U,1 422.7?221.7 U) and liver MDA con-tent(5.28?0.93 ?mol/g),caspase-3 activitiy(optical density value(4.69)?1.02) and TNF-? level(256.3?27.3 ng/L) combined with a remarkable reduction in liver SOD activity(45.9?14.8 U/mg) as compared with the control rats.Histopathological observations revealed severe damage in the liver and prominent hepatocyte apoptosis took place in CCl_4treated rats.However,pretreatment with hemin could induce high expression of HO-1 protein and exert potent protective effects against liver injury,as demonstrated by a significant decrease in ALT,AST levels(287.1?24.3 U,246.2?21.7 U) and MDA concentration(3.27?1.34 ?mol/g),reduction in caspase-3 activity(optical density value 2.49?1.47) and TNF-? level(132.6?19.5 ng/L),as compared with the CCl_4-treated rats.Moreover,hepatocyte apoptosis and liver injury were both attenuated remarkably in the liver of rats pretreated with hemin.In contrast to hemin administration,single injection of exogenous CO produced the same protective effects,as indicated by the remarkable reduction of ALT,AST levels and caspase-3 activity and TNF-a levels.Conclusion: The above results suggest that HO-1/CO system has a potent protective effect on acute liver injury induced by carbon tetrachloride in rats.Induction of HO-1 expression and low concentration of CO can inhibit the progress of hepatic damage,which might be due to the alleviation of lipid peroxidation and reduction of caspase-3 activity or inhibition of TNF-? level.

Study on monitoring and clearing of organophosphate in blood in organophosphate poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the new method of monitoring and clearing organophosphate in blood during single or mixed organophosphate(OP) poisoning.</p><p><b>METHOD</b>(1) Mixed equal volumes of blood of OP poisoned rat and healthy rat, then determine whole blood cholinesterase (ChE) activity. The descending range of ChE activity represents the level of residual OP in blood. (2) Poisoned rats by single or mixed OP pesticides were injected with 5% NaHCO3 15 ml/kg intraperitoneally, then the level of OP in blood was detected.</p><p><b>RESULTS</b>(1) The monitoring results of blood residual OP by gas chromatography were similar to that by "Mixes blood method", which showed significant difference(P < 0.05) from that before OP administration. (2) NaHCO3 injection could not improve the toxic symptoms and whole blood or brain ChE inhibition in 10 CP poisoned rats, blood residual OP level was also not affected, but lung pathological changes by OP such as interstitial inflammation and oedema showed some relief.</p><p><b>CONCLUSION</b>The monitoring of blood ChE by "mixed blood method" may reflect the general level of the blood residual OP within the range of exposure dose. The effect of NaHCO3 was not satisfactory, but it may improve OP-induced lung pathological changes.</p>

An experimental study of therapeutic effect of ACEI on chemical-induced ARDS in rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the role of angiotensin converting enzyme inhibitor (ACEI) in the treatment of acute respiratory distress syndrome (ARDS).</p><p><b>METHODS</b>Changes in physiological and biochemical indexes, and circulating endothelial cells (CEC) were observed in rats of oleic acid-induced ARDS with ACEI-Captopril (Cap) therapy and controls, respectively.</p><p><b>RESULTS</b>Under the normal systemic blood pressure, Captopril therapy showed good effect on ARDS in rats. Two hours after administration of Captopril, their pulmonary arterial pressure reduced to (14.43 +/- 1.51) mm Hg (1 mm Hg = 0.133 kPa), approximating to normal level, from (23.50 +/- 5.79) mm Hg. The number of CEC, which reflected injuries in pulmonary capillaries, decreased to (4.25 +/- 0.20)/0.9 micro l from (6.88 +/- 1.90)/0.9 micro l. Value of oxygen pressure in arterial blood (PaO(2)) increased to (70.48 +/- 9.54) mm Hg from (35.08 +/- 4.59) mm Hg. In the mean time, ratio of wet to dry lung weight was returned to nearly normal. So, it indicated that high-dose of oleic acid could only induce mild lung injury, and the development of ARDS was obviously inhibited by ACEI.</p><p><b>CONCLUSIONS</b>ACEI may effectively depress pulmonary arterial hypertension, block the development of ARDS, and have certain good protective effect on pulmonary capillary endothelia.</p>

Role of Free Radicals in Lung Cancer Induced by Physical and Chemical Factors / 环境与健康杂志

The free radicals are some substances which have important influence on the human health. They both have salutary and harmful aspects to the human health. The role of free radicals in the lung cancer induced by physical and chemical factors such as smoking, occupational dust particles, metal ions, quartz, asbestos were briefly discussed in this article.