Activating effect of extracellular histones on heparinase in chlorine-induced acute lung injury / 中国职业医学

OBJECTIVE: To investigate the induction and activation of heparinase by extracellular histones in acute respiratory distress syndrome(ARDS) induced by chlorine in mice.METHODS: The specific pathogen free adult male C57 BL/6 mice were randomly divided into control group, chlorine injured group, histone injured group, anti-histone antibody group and heparinase inhibitor group, with six mice in each group.The mice in the control group and histone injured group were exposed to clean air, and the mice in the other three groups were exposed to chlorine gas at a dose of 580.0 mg/m~3 for 30 minutes by systemic dynamic inhalation.Mice in the histone injured group were injected with 50 mg/kg body weight calf thymus histone by tail vein.One hour before exposure, mice in the anti-histone antibody group were pretreated with 20 mg/kg body weight anti-histone H4 antibody by tail vein injection, and mice in the heparinase inhibitor group were injected with 2 mg/kg body weight OGT2115(heparinase inhibitor). The other three groups were given equal volume of 0.9% sodium chloride solution by tail vein injection. After 24 hours of exposure, arterial blood was collected for blood gas analysis and the lung tissue was collected for histopathological examination. The protein level of heparinase in lung tissue were detected using enzyme-linked immunosorbent assay, and the activity of heparinase were detected by measuring the product of heparan degradation. The protein expression of pro-heparinase and active heparinase were detected by Western blotting.RESULTS: The dyspnea developed of mice in the chlorine injured group and histone injured group, diffuse inflammation occurred in lung tissue, the oxygenation index in arterial blood decreased(all P<0.05), and the protein level and activity of heparinase in lung tissue, as well as the relative expression of pro-heparinase and active heparinase were increased compared with the control group(all P<0.05). The dyspnea, hypoxemia and acute lung injury of mice in the anti-histone antibody group were alleviated, and the protein level of heparinase in lung tissue, as well as the relative expression levels of pro-heparinase and active heparinase were decreased(all P<0.05), compared with chlorine injury group and histone injury group.The dyspnea, hypoxemia and acute lung injury were alleviated in the heparinase inhibitor group, and the activity of heparinase and the relative expression of pro-heparinase in the lung tissue were decreased compared with the chlorine injury group(all P<0.05). CONCLUSION: During the occurrence and development of chlorine-induced ARDS in mice, extracellular histones aggravate lung injury by inducing the expression and activation of heparinase. Acute lung injury can be alleviated by inhibiting the expression and activation of heparinase.

Differentiation and Treatment Thinking of Infertility from “Disease Prevention” to“Pregnancy Relying on Regulating Menstruation” / 中国中医药信息杂志

Ovarian function is the basis of female reproduction. Due to various causes of ovarian function, manstruation, menstrual cramps and infertility may appear. For infertility caused by ovaries, if the roots are traced, the roots may be low ovarian function. The idea of "disease prevention" should be throughout the treatment. "Pregnancy relying on regulating menstruation" theory should be followed, with a purpose to realize the early identification and early treatment.

Early Biomarkers in 1H Nuclear Magnetic Resonance Spectroscopy of Striatal Pathological Mechanisms after Acute Carbon Monoxide Poisoning in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>In vivo Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to evaluate the levels of specific neurochemical biomarkers of pathological mechanisms in the brain.</p><p><b>METHODS</b>We conducted T2-Weighted Magnetic Resonance Imaging (MRI) and 1H-MRS with a 3.0-Tesla animal MRI system to investigate the early microstructural and metabolic profiles in vivo in the striatum of rats following carbon monoxide (CO) poisoning.</p><p><b>RESULTS</b>Compared to baseline, we found significant cortical surface deformation, cerebral edema changes, which were indicated by the unclear gray/white matter border, and lateral ventricular volume changes in the brain. A significant reduction in the metabolite to total creatine (Cr) ratios of N-acetylaspartate (NAA) was observed as early as 1 h after the last CO administration, while the lactate (Lac) levels increased marginally. Both the Lac/Cr and NAA/Cr ratios leveled off at 6 h and showed no subsequent significant changes. In addition, compared to the control, the choline (Cho)/Cr ratio was slightly reduced in the early stages and significantly increased after 6 h. In addition, a pathological examination revealed mild cerebral edema on cessation of the insult and more severe cerebral injury after additional CO poisoning.</p><p><b>CONCLUSION</b>The present study demonstrated that 1H-MRS of the brain identified early metabolic changes after CO poisoning. Notably, the relationship between the increased Cho/Cr ratio in the striatum and delayed neuropsychologic sequelae requires further research.</p>

Dynamic changes of hemorheology in rats after carbon monoxide poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the startup detail of circulation dysfunction and its role in the progress of delayed neuropsychologic sequelae (DNS) after carbon monoxide (CO) poisoning with comparison with the model of ischemia-reperfusion.</p><p><b>METHODS</b>The ischemia-reperfusion rat model was established by Pulsinelli-Brierley method, and the CO poisoning rats model by i.p. injected with CO repeatedly respectively, and the rats were identified with DNS following the experiment of pathology and the ethnology.</p><p><b>RESULTS</b>The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen increased significantly immediately after reperfusion, and recovered gradually with the ischemia-reperfusion rat model. The whole blood viscosity decreased significantly immediately after CO treated i.p. Especially at low shear rate, the hematocrit also declined remarkably in the early stage after CO treatment. But 1day later, these parameters turned to the trend of the ischemia-reperfusion rats. There was a prominent elevation of both indexes until the 14th day following CO injection i.p.</p><p><b>CONCLUSION</b>There are significantly sustained hyper-coagulation and hyper-viscosity with circulation in rats after CO poisoning compared with ischemia-reperfusion model during the period of DNS, which might contribute to increase cerebral circulation resistance, blocked blood flow, and deteriorate hypoxemia in progression of DNS.</p>

Changes of heine oxygenase-1 and its product carbon monoxide in acute liver injury / 中华急诊医学杂志

Objective To investigate dynamic changes of heme oxygenase-1 and carbon monoxide in acute liver injury induced by carbon tetrach loride(CCl_4)in rats.Method Male SD rats were randomly allocated to induce acute liver injury by CCl_4 injection.Hepatic HO activity was examined at different time point following CCl_4 treatment.Expression and location of HO-1 protein was determined by western blot and immunohistochemical methods.Serum ALT,AST levels and hepatic SOD,MDA concentrations were also analyzed.Results Administration of CCl_4 to rats caused a marked hepatic damage,characterized by significant elevation of serum ALT,AST levels and liver MDA content combined with a remarkable reduction in liver SOD activity.HO activity was elevated significanfly in a time-dependant manner after CCl_4 injection,while the expression of HO-1 protein increased remarkably from 6 to 36 hours.CO concentration in the liver homogenate of control rats remained very low but was elevated significantly after CCl_4 treatment,which was in accordance with changes of HO-1. Conclusions HO-1 activity and protein expression as well as CO production are higher in rats with acute liver injury induced by CCl_4 than in control group.HO-1/CO system plays an important role in the pathogenesis of acute hepatic damage and may have potent protective effect against liver injury.

Preventive effects and mechanism of heme oxygenase-1 activation on acute respiratory distress syndrome in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the possible mechanism of heme oxygenase-1 (HO-1) induction for its protective effects on acute respiratory distress syndrome (ARDS).</p><p><b>METHODS</b>The production of HO-1 was induced by hemoglobin (Hb) injection into oleic acid (OA) induced ARDS rats. Western blot and RT-PCR techniques were used to observe the induction of HO-1 in vivo. Both the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). Combined with blood gas analysis and other indexes, the effect of HO-1 on ARDS could be clearly manifested.</p><p><b>RESULTS</b>The expression of HO-1 mRNA was increased significantly 16 h after Hb injection, and the protein expression of HO-1 was also obviously increased 24 h later (P < 0.01). The levels of TNF-alpha and IL-8 in both serum and BALF were significantly lower in Hb + OA group than in OA group (P < 0.01). Arterial blood PaO(2), oxygen saturation, and oxygenated index in Hb + OA group [(56.28 +/- 6.71) mm Hg, (79.53 +/- 5.82)%, and (258.81 +/- 29.37) mm Hg respectively] were higher than in OA group [(35.08 +/- 4.59) mm Hg, (55.80 +/- 12.76)%, and (167.86 +/- 21.94) mm Hg]. Lung wet and dry weight, and pathological changes were also improved.</p><p><b>CONCLUSION</b>The production of HO-1 was successfully induced by hemoglobin in vivo. Protective effects of HO-1 on ARDS might be related to the decreasing in inflammatory factors, such as TNF-alpha and IL-8.</p>

A study of high altitude environment affecting on worker's health during the constructing Qinghai-Xizang railway / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study high altitude environment affecting on worker's health</p><p><b>METHODS</b>Using the cohort study, the altitude reaction was investigated and the WBC, RBC, Hb and oxygenation indexes were measured on workers in several periods, namely, acclimatization period, initially arrived high altitude and resident 90 days.</p><p><b>RESULTS</b>The 83.3% of men had altitude reactions with different kinds at initially arrived high altitude. The headache was the most. The rate of abnormal blood pressure increased with altitude and resident time (P < 0.01). The rate of 90 day's group was 41.7%. The rise of diastole pressure was obvious (P < 0.01). As the beginning of arrived highland, the increase of WBC, RBC were significant (P < 0.01). The increase of Hb appeared only in 90 day's group. The level of malondialdehyde (MDA) obviously increased during acclimatization period and increased with altitude and resident time (P < 0.01). The activity of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) increased significantly in 90 day's group [(222.36 +/- 36.52) x 10(3) U/L, (158.49 +/- 14.42) U/L, (45.74 +/- 8.31) NU/ml respectively] (P < 0.01).</p><p><b>CONCLUSION</b>The high altitude environment may result in the abnormal blood pressure, the rise of diastolic pressure was important. It lead to the increase of WBC, RBC, Hb. It initiated activity of oxygenation reaction. The symptoms of headache, dizziness, loss of appetite and insomnia appeared as working in high altitude environment.</p>

Changes of carbon monoxide, nitric oxide levels and heme oxygenase system in acute respiratory distress syndrome induced by oleic acid / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate possible role of carbon monoxide (CO) and heme oxygenase (HO) in the pathogenesis of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) and to compared with that induced by nitric oxide (NO).</p><p><b>METHODS</b>ARDS model was established in rats by oleic acid injection and concentrations of CO and NO in pulmonary arterial, carotid jugular blood and bronchoalveolar lavage fluid (BALF) were measured sequentially. Immunohistochemical method was used to determine the expression of HO in the lung.</p><p><b>RESULTS</b>Pulmonary arterial pressure in ARDS rats elevated 10 min after OA injection [(13.80 +/- 1.87) mm Hg to (19.51 +/- 5.02) mm Hg]. At 0.5 h after OA injection, concentration of CO in pulmonary artery began to increase and was markedly higher at 2 h than that in control rats [(0.135 +/- 0.010) g/L versus (0.116 +/- 0.005) g/L] (P < 0.01), also higher than that in carotid artery [(0.117 +/- 0.013) g/L] and in jugular vein [(0.107 +/- 0.018) g/L] in the same group, and maintained at a relatively high level thereafter. Concentration of CO in BALF also increased at 0.5 - 24 h and diminished at 72 h, as compared with that in controls. Concentration of NO in blood of pulmonary and systemic circulation all elevated markedly at 0.5 h and 2 h after OA injection, and then declined to normal at 12 h. Concentration of NO in BALF was significantly higher than that in controls. Arterial blood gas analysis showed that PaO2 markedly decreased in ARDS rats, especially at 2 h after OA injection. HO-2 could be expressed in the lung tissues of normal rats with immunohistochemical method, the strongest in epithelial cells of the bronchi, and HO-1 could only be expressed in pulmonary blood vessel walls, bronchial epithelial cells, alveolar epithelial cells and inflammatory cells of ARDS rats, lasting for 72 h after OA injection, consistent with that of CO level.</p><p><b>CONCLUSION</b>ARDS rats showed a lastecl increase of CO level in pulmonary blood circulation, suggesting CO/HO system might play a more important role in modulation of blood vessel tension than NO might do in pathogenesis of ARDS.</p>

Study of T lymphocyte rDNA transcription activity in chronic benzene poisoning patients / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the changes in peripheral blood T lymphocyte rDNA transcription activity and to study the significance of immune monitoring for patients with chronic benzene poisoning.</p><p><b>METHODS</b>Venous blood samples were withdrawn from 39 patients with chronic benzene poisoning, 20 patients with malignant disease and 22 healthy controls. Cell culture, argyrophil staining method, I-CLQ cell image analysis system were used in this study. rDNA transcription activity which was expressed by the ratio of integrated area (IA) of nucleolus to that of nucleus, and the ratio of integrated optical density (IOD) of argyrophilic nucleolus to that of argyrophilic nucleus.</p><p><b>RESULTS</b>(1) The value of IA and IOD in chronic benzene poisoning patients (7.95% +/- 1.13% and 7.15% +/- 1.15% respectively) were lower than those in controls (9.59% +/- 1.26% and 8.92% +/- 1.18% respectively), P < 0.01. The value of IA and IOD in chronic moderate benzene poisoning patients (6.54% +/- 0.88%) and (5.47% +/- 0.80%) were lower than those to be observed (7.98% +/- 1.06% and 7.13% +/- 0.96% respectively) as well as in mild poisoning patients (8.19% +/- 1.06% and 7.44% +/- 1.06% respectively), P < 0.05. (2) The value of IA and IOD in malignant group (4.10% +/- 1.50%, 3.67% +/- 1.42%) were much more lower than those in controls and in chronic benzene poisoning patients (P < 0.01).</p><p><b>CONCLUSION</b>rDNA transcription activity may be an index to monitor the cellular immune function of chronic benzene poisoning patients.</p>

Study on the changes in circulating endothelial cells and hemorheology of lung in rats with acute lung injury by chemicals / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of pulmonary circulation obstacle in chemicals-induced acute lung injury and its clinical significance.</p><p><b>METHOD</b>Pulmonary arterial intubation, circulating endothelial cells (CEC) isolation and hemorheology detection technique were used to observe the changes of CEC numbers and hemorheology in rat pulmonary vascular system during oleic acid-induced acute lung injury (ALI).</p><p><b>RESULTS</b>The numbers of CEC were obviously increased even in the early phase of ALI [from (2.06 +/- 0.48)/0.9 micro l to (5.50 +/- 0.54)/0.9 micro l]; there was no obvious change in whole blood viscosity under high shear rate (200 s(-1), 30 s(-1)) but the whole blood viscosity and hematocrit were remarkably increased in pulmonary artery blood at low shear rate (5 s(-1), 1 s(-1)) (P < 0.05). Erythrocytes had increasing tendency, whereas platelets were also decreased but there was no statistical significance.</p><p><b>CONCLUSION</b>The deterioration of pulmonary circulation may be the key point in the pathogenesis of ALI; the injury and dysfunction of pulmonary capillary endothelial cells (PCEC) may be the common starting phase in the pathological processes of ALI; the detection of CEC may offer a new valuable and sensitive index for diagnosis of ALI.</p>