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Objective To investigate the protective effect and underlying mechanism of the superoxide dismutase mimic, manganese (Ⅲ) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), on paraquat (PQ) -induced lung epithelial-like cell injury. Methods Alveolar epithelial-like cells (A549) were pretreated with 10 μmol/L of MnTMPyP for 1.5 h and then cultured with or without PQ (750 μmol/L) for 24 h. Cell survival was determined using the MTT assay. Reactive oxygen species (ROS) production and Ca2+ levels were measured using flow cytometry. Glutathione reductase (GR) activity was determined using spectrophotometry. Expressions of the endoplasmic reticulum (ER) stress proteins, glucose regulatory protein 78 (Grp78) and C/EBP homologous protein (CHOP), were measured using Western blotting. Results Cell viability and GR activity were decreased, but ROS production, cytoplasmic Ca2+ levels, and expressions of Grp78 and CHOP were all increased in the PQ group compared to those in the control group. There were no statistically significant changes in the MnTMPyP group. Cell viability and GR activity were increased, while ROS production, cytoplasmic Ca2+ levels, and expressions of Grp78 and CHOP were all significantly reduced in the MnTMPyP group compared to those in the PQ group. Conclusion MnTMPyP effectively reduced PQ-induced lung epithelial-like cell injury, and the underlying mechanism is related to antagonism of PQ-induced ER stress and oxidative stress.
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Objective To find out the clinical indicators related to prognosis in patients with acute mushroom poisoning, and approach its correlation with prognosis. Methods Clinical data of patients with mushroom poisoning admitted to the First Hospital of China Medical University, the Ninth People's Hospital of Shenyang, Xiuyan Central People's Hospital, and Fushun Central Hospital from August 2015 to August 2017 were retrospectively analyzed. The biochemical indicators within 24 hours after admission, sequential organ failure assessment (SOFA) score, model for end-stage liver disease (MELD) score, whether plasmapheresis (PE) was carried out or not and 28-day prognosis of patients were collected. According to prognosis, the patients were divided into death group and survival group, and the differences in above parameters between the two groups were compared. Spearman or Pearson correlation method was used to analyze the relationship between MELD score and prognosis. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of MELD score for prognosis. Further analysis of the patients receiving PE treatment was conducted. Results A total of four Liaoning hospitals with 89 patients with mushroom poisoning were enrolled, with 6 died within 28 days, and 83 survived. There were 17 patients with severely impaired liver and coagulant functions accepted PE treatment, with 6 patients died within 28 days, and 11 survived. ① In 89 patients, compared with survival group, MELD score, prothrombin time (PT), activated partial thromboplastin time (APTT), total bilirubin (TBil), international normalized ratio (INR), blood glucose (Glu), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) in death group were significantly increased [MELD score: 32.34 (28.31, 41.06) vs. 8.76 (3.77, 21.19), PT (s): 53.5 (52.4, 113.2) vs. 14.5 (13.8, 19.5), APTT (s): 58.6 (48.9, 70.8) vs. 36.9 (34.4, 43.2), TBil (μmol/L): 134.8 (31.3, 155.6) vs. 21.5 (15.1, 41.4), INR: 6.0 (5.6, 14.7) vs. 1.2 (1.1, 1.5), Glu (mmol/L): 9.2 (9.0, 11.0) vs. 6.6 (5.7, 7.8), ALT (U/L):5 923.0 (1 105.0, 6 000.0) vs. 35.0 (18.0, 1 767.0), GGT (U/L): 49.0 (32.0, 57.0) vs. 25.0 (16.0, 41.0), all P < 0.05], but the prothrombin activity (PTA), albumin (ALB), serum Na+, Cl- were significantly decreased [PTA: 13.0% (6.0%, 14.0%) vs. 80.0% (61.0%, 87.0%), ALB (g/L): 31.1 (29.8, 39.0) vs. 42.4 (37.9, 44.3), Na+(mmol/L): 126.5 (122.4, 131.0) vs. 137.0 (134.9, 141.0), Cl- (mmol/L): 93.5 (87.6, 95.0) vs. 104.0 (101.3, 106.0), all P < 0.05]. Spearson correlation analysis showed that MELD score of patients with mushroom poisoning was positively correlated with the 28-day mortality (r = 0.423, P = 0.001). ROC curve analysis showed that the area under ROC curve (AUC) of MELD score for prognosis of patients with mushroom poisoning was 0.926; when the cut-off value was 27.30, the sensitivity was 100%, and the specificity was 84.3%. ② In 17 patients who accepted PE treatment, compared with survival group, the MELD score, TBil, Glu, and ALT in the death group were significantly increased [MELD score: 36.81±5.18 vs. 29.01±5.23, TBil (μmol/L): 145.2±13.9 vs. 93.2±44.0, Glu (mmol/L): 9.1±1.9 vs. 6.0±2.7, ALT (U/L): 5 961.5±44.5 vs. 3 932.9±1 625.7, all P < 0.05], and Cl- was significantly lowered (mmol/L: 94.3±1.2 vs. 100.5±5.7, P < 0.05), but SOFA score showed no significant difference (5.83±2.71 vs. 5.91±1.58, P > 0.05). Correlation analysis showed that the MELD score in patients with mushroom poisoning who accepted PE treatment was positively correlated with 28-day mortality (r = 0.355, P = 0.001), but no correlation with SOFA score was found (r = 0.427, P = 0.087). ROC curve analysis showed that the AUC of MELD score in the prediction of mushroom poisoning patients undergoing PE treatment was 0.545; when the cut-off value was 32.19, the sensitivity was 33.3%, and the specificity was 100%. Conclusions In mushroom poisoning patients, especially those undergoing PE treatment, the higher the MELD score, the higher the mortality is. MELD score could assess the prognosis of patients with acute mushroom poisoning.
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Objective To investigate the apoptosis mechanism induced by paraquat (PQ) in human type Ⅱ alveolar epithelial-like A549 cells.Methods A549 cells were cultured in vitro.The cells in the experimental group were exposed to various concentrations of PQ (50,100,150,and 200 μmol/L),while those in the control group were cultured in RPMI1640 medium.After treatment for 24 and 48 h,the cell survival rate was assessed by MTT assay.Morphological changes in the nuclei were observed by Hoechst 33258 fluorescence staining.Cellular apoptosis and mitochondrial transmembrane potential were assayed by flow cytometry.The activities of caspase-3 and caspase-9 were assayed by spectrophotometry.Western blotting was used to analyze the expression of proteins in the Bcl-2 family,such as Bcl-2,Bcl-xL,Bax,and Bak.Results PQ exhibited significant anti-proliferative activity in A549 cells.PQ-treated A549 cells were subjected to Hoechst 33258 staining.The hallmarks of apoptosis were detected,and the degree of apoptosis increased.Mitochondrial membrane potential was decreased,the levels of active caspase-3 and caspase-9 increased,the expression of Bcl-2 and Bcl-xL was decreased,and the expression of Bax and Bak was increased.These effects occurred in concentration-and time-dependent manners.Conclusion PQ efficiently induced intracellular apoptosis through the mitochondrial pathway in A549 cells.
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Objective To investigate the role of Toll?like receptor 4(TLR4)in acute lung injury induced by paraquat(PQ)poisoning. Meth?ods Twenty wild?type mice(C57BL/6J)and TLR4 knockout mice(C57BL/10ScN)were randomly divided into 4 groups:WT group,WT+PQ group,TLR4 gene knockout(TLR4?ko)group and TLR4?ko+PQ group,with 10 mice in each group. After paraquat treatment for 24 hours,mice were euthanized and sacrificed. TLR4 expression and pro?inflammatory cytokines were evaluated. Results After 24 hours of intraperitoneal injec?tion of PQ,wild?type mice showed significant acute lung injury,including decreased oxygen tension in blood gas,pathological changes in the acute stage of lung injury and increased TLR4 expression(accompanied by increased levels of TNF?α,IL?1βand NF). TLR4?deficient mice exhibited significantly reduced level of paraquat?induced lung injury. Conclusion TLR4 may be required as a mediator and play an important role in acute lung injury induced by paraquat. Inhibition of TLR4 signaling has protection of lung injury induced by PQ.
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Objective To clarify the role and significance of Toll?like receptor 4(TLR4)in myocardial damage following paraquat(PQ)poisoning in mice. Methods Male wild type C57BL/6J mice(WT)and male TLR4 deficient mice(TLR4?ko)were divided into four groups in the study:(1)control group(WT mice,n=6);(2)TLR4?ko group(TLR4?ko mice,n=6);(3)WT+PQ group(WT mice,n=30);(4)TLR4?ko+PQ group (TLR4?ko mice,n=30). The mice in group 1 and group 2 were injected intraperitoneally with saline;mice in group 3 and group 4 were injected in?traperitoneally with 75 mg/kg of PQ. At 2 h,4 h,8 h,16 h and 24 h after PQ administration,6 mice of WT+PQ group and TLR4?ko+PQ group were euthanized and the heart tissue specimens were harvested. All the specimens were analysed by histology,while the expression of TLR4 mRNA was only detected in samples of WT+PQ mice. The specimens at 2 h,8 h and 24 h after PQ administration were used for cytokines detection for WT+PQ group and TLR4?ko+PQ group;in addition,Western blot analysis was performed for WT+PQ group. At 8 h after treatment,control mice and TLR4?ko mice were euthanized by the same method. Mice were anesthetized for cardiac geometry and functional assessment using a 2?D guide M?mode echocardiography at 8 h following injection of either PQ or saline. Results During myocardial damage due to PQ exposure in WT+PQ mice,obvious histopathological changes were observed,as well as a noticeable decrease of heart function and increased expressions of TNF?αand IL?1β. Compared with the WT mice,TNF?αand IL?1βprotein levels,changes in heart function and histopathological changes were significantly attenuated following PQ exposure in myocardial damage in TLR4?ko mice. Conclusion The TLR4gene is involved with in heart functional injury and histopathological changes in myocardial damage following PQ poisoning in mice,which may through the regulation of TNF?αand IL?1βexpression. Our findings indi?cate that TLR4 plays an important role in mediating myocardial injury due to PQ.
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Objective To study the changes of transforming growth factor-β1(TGF-β1) in pulmonary fibrosis induced by paraquat (PQ) with immunohistochemistry method. MethodsA total of 58 C57BL/6J male mice were randomly (random number) divided into the experimental group and control group. Pulmonary fibrosis was induced by intra-peritoneal injection of PQ in dose of 10 mg/kg into the mice of experimental group (n = 48), while physiological saline was used instead in mice of control group (n = 10). The mice of experimental group were sacrificed 2, 5, 7 and 14 days after PQ poisoning and the mice of control group were sacrificed on the 7th day after saline administration. Lungs of mice were taken and histological changes in lungs were evaluated by haematoxylin-eosin stain, and TGF-β1 was determined with immunohistochemistry method. The integrated optical density (iOD) value of TGF-β1 was measured and analyzed. ResultsThe TGF-β1 was markedly increased in macrophages during the genesis of pulmonary fibrosis induced by PQ. As the course of fibrosis progressed, the positive staining of TGF-B1 was mainly seen in macrophages and neutrophil's cytoplasm. On the 14th day after PQ poisoning, TGF-β1-positive cells were also detected in the fibroblast and myo-fibroblast inside the fibroblastic foci. Compared with the control group, the iOD value of TGF-β1 increased in experimental group (P ＜ 0. 01 ) and it gradually upgraded during the course of fibrosis. Conclusions The TGF-β1 significantly increased during the course of pulmonary fibrosis induced by PQ and played an important role in the pathogenesis of the disease.
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Objective To analyze analgesics administration from July 2005 to July 2006 in emergency rooms of the First, the Second and Fourth Affiliated Hospitals of China Medical University in order to provide a reference for clinically rational administration. Method The data of 2313 prescriptions with analgesics administered during one-year period were analyzed in many respects including the overview of the prescriptions, the frequency of anal-gesics administration, the system of defined daily doses (DDDs) and drug utilization index (DUI) of narcotic anal-gesics were analyzed, and a survey of 200 patients managed with some of those analgesics was done by using ques-tionaire as they were admitted to and discharged from the emergency room. The pain intensity was evaluated by a 10-point numerical rating scale (NRS). The respondents, excluding the mute or deaf, police custody, victims of domestic violence,mental disorder and age under 14,rated the levels of satisfaction with medication for pain relief. The data of frequency and percentage of the administration of analgeics were analyzed,and the scores of NRS were evaluated with the Paired-samples t -test. Results Most of analgesics were in the form of parenteral route usage, of which anisodamine and bucinnazine were employed in large proportion, and a small number of them was in the form of tablets. Trauma was the commonest cause of pain. Of the narcotic analgesics, meperidine was the most com-monly used analgesics, and its DDDs and DUI were much lower than that of WHO limits. Of the 200 patients, 71.5% patients rated a considerably high satisfaction with scores of (7.47 ±2.21) and (5.00 ± 3. 16) by NRS before and after medication,respectively ( ( -value 23.38,P < 0.01) .The patients presenting pain intensity with a scores of 4 or greater accounted for 57.5% . Conclusions The patients suffering from pain could lie rationally treated in the emergency rooms of those three hospitals. Narcotic analgesics should be cautiously employed, and there is room for improvement in pain management practice in emergency room.