Rationale:Multi-organ failure is a symptom of paraquat poisoning,resulting in high mortality and morbidity rates.Though paraquat is widely available,poisoning through inhalation is rare.Patient’s Concern:A 37-year-ol...Rationale:Multi-organ failure is a symptom of paraquat poisoning,resulting in high mortality and morbidity rates.Though paraquat is widely available,poisoning through inhalation is rare.Patient’s Concern:A 37-year-old male reported to the emergency department with complaints of vomiting after an alleged history of inhalation of paraquat while at work.Diagnosis:Paraquat poisoning.Interventions:Supportive management along with multiple sessions of hemodialysis.Outcomes:Renal complications caused by paraquat were improved after multiple sessions of hemodialysis.However,the patient developed respiratory complications and later due to persistent hypoxemia and non-responsive to supportive therapy,he succumbed to his illness.Lessons:Acute kidney injury is a complication of paraquat poisoning.However,kidney involvement with the inhalational mode is rare.It is caused by reduction and oxidation cycles,as well as the formation of reactive oxygen species,necessitating hemodialysis as the treatment.Without a clear history,a specific clinical trait,or a diagnostic test,diagnosis can be difficult.Our case thus highlights the inhaled paraquat poisoning,presenting with acute kidney injury with late respiratory impairment as a consequence.展开更多
Paraquat (PQ, methyl viologen) was widely used in agricultural production throughout the world in 1962 for its efficient herbicidal activity. PQ was also highly toxic drug. About 5 mL medicine including 20% paraquat w...Paraquat (PQ, methyl viologen) was widely used in agricultural production throughout the world in 1962 for its efficient herbicidal activity. PQ was also highly toxic drug. About 5 mL medicine including 20% paraquat was life-threatening that can cause poisoning. In 1966, some people died because of PQ poisoning. Most patients had acute respiratory distress syndrome after 2 wk, and 70% of them died due to the lack of effective detoxification drugs. Thus, it was particularly important to understand the pathogenesis of PQ poisoning and give some effective treatments. This article will review the toxicological mechanism and treatment on PQ poisoning of acute lung injury.展开更多
BACKGROUND There is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication(APP).AIM To optimize a predictive scoring system for mortality in children with APP.MET...BACKGROUND There is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication(APP).AIM To optimize a predictive scoring system for mortality in children with APP.METHODS A total of 113 children with APP from January 1,2010 to January 1,2020 were enrolled in this study.These patients were divided into survivors and nonsurvivors.We compared the clinical characteristics between the two groups and analyzed the independent prognostic risk factors.The survival rates of patients with different values of the pediatric critical illness score(PCIS)were assessed using kaplan-meier survival analysis.The best scoring system was established by using the area under the receiver operating characteristic curve analysis.RESULTS The overall mortality rate was 23.4%.All non-survivors died within 20 days;48.1%(13/27)died within 3 days,and 70.3%(19/27)died within 7 days.Compared to survivors,the non-survivors were older,had higher white blood cell count,alanine aminotransferase(ALT),aspartate aminotransferase,serum creatinine,blood urea nitrogen,glucose,and pediatric early warning score,and had lower platelet count,albumin,Serum sodium(Na+)and PCIS.ALT and PCIS were the independent prognostic risk factors for children with APP.The survival rate of children classified as extremely critical patients(100%)was lower than that of children classified as critical(60%)or noncritical(6.7%)patients.The specificity of ALT was high(96.51%),but the sensitivity was low(59.26%).The sensitivity and specificity of ALT combined with PCIS were high,92.59%and 87.21%,respectively.The difference in mortality was significantly higher for ALT combined with PCIS(area under the receiver operating characteristic:0.937;95%CI:0.875-0.974;P<0.05).CONCLUSION In our study,ALT and PCIS were independent prognostic risk factors for children with APP.ALT combined with PCIS is an optimal predictive mortality scoring system for children with APP.展开更多
Objective: To investigate the effects of hemoperfusion combined with hemodialysis on target organ damage in patients with acute paraquat poisoning. Methods: A total of 42 patients with acute paraquat poisoning who wer...Objective: To investigate the effects of hemoperfusion combined with hemodialysis on target organ damage in patients with acute paraquat poisoning. Methods: A total of 42 patients with acute paraquat poisoning who were admitted and treated in our hospital between December 2013 and October 2017 were selected as the research subjects, and their therapies were reviewed and used to divide them into the control group (n=20) who received hemoperfusion alone and the combined treatment group (n=22) who received hemoperfusion combined with hemodialysis. The differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were compared between the two groups of patients immediately after admission, after 1 d of treatment and after 3 d of treatment. Results: Immediately after admission, the differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were not statistically significant between the two groups. After 1d of treatment and after 3 d of treatment, kidney function indexes Scr, BUN and β2-MG levels in peripheral blood of combined treatment group were lower than those of control group at corresponding time points respectively;liver function indexes ALT, AST, TB and ALP levels in peripheral blood were lower than those of control group at corresponding time points respectively;lung function indexes PaO2, BE and PCO3- levels in arterial blood were higher than those of control group at corresponding time points respectively whereas PaCO2 levels were lower than those of control group at corresponding time points respectively. Conclusion: Compared with hemoperfusion alone, hemoperfusion combined with hemodialysis is more advantageous in protecting the functions of liver, kidney, lungs and other target organs of patients with acute paraquat poisoning.展开更多
BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving...BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.展开更多
BACKGROUND: Paraquat (PQ) is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological ...BACKGROUND: Paraquat (PQ) is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 (HSP70) in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS: Seventy-two adult healthy SD rats were randomly divided into a control group (group A, n=24), a poisoning group (group B, n=24), and an ulinastatin group (group C, n=24). The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS: Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi? cantly at all intervals (P〈0.05). The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in? ltration and local hemorrhage, whereas those of group C were signi? cantly lessened.CONCLUSION: Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.展开更多
AIM To report our experience of acute kidney injury(AKI) developed after exposure to poisonous substance.METHODS Retrospective study where data was collected from case records of patients coming to this institute duri...AIM To report our experience of acute kidney injury(AKI) developed after exposure to poisonous substance.METHODS Retrospective study where data was collected from case records of patients coming to this institute during January 1990 to May 2016.This institution is a tertiary care center for renal care in the metropolitan city of Karachi,Pakistan.History of ingested substance,symptoms on presentation,basic laboratory tests on arrival,mode of treatment and outcome were recorded from all patients and are presented here.Patients developing AKI after snake envenomation or scorpion stings are not included in this study.RESULTS During studied period 184 cases of AKI developing after poisoning were seen at our institution.The largest group was from paraphenyline diamine poisoning comprising 135 patients,followed by methanol in 8,organophosphorus compounds in 5,paraquat in 5,copper sulphate in 5,tartaric acid in 4,phenobarbitone in 3 and benzodiazipines,datura,rat killer,fish gall bladder,arsenic,boiler water,ammonium dichromate,acetic acid and herbs with lesser frequency.In 8 patients multiple substances were ingested in combination.Renal replacement therapy was required in 96% of patients.Complete recovery was seen in 72.28% patients,20% died during acute phase of illness.CONCLUSION It is important to report poisonous substances causing vital organ failure to increase awareness among general population as well as health care providers.展开更多
Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ pathway.Methods:Male Sprague Dawley rats were divided into fou...Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ pathway.Methods:Male Sprague Dawley rats were divided into four experimental groups:control,PQ,PQ+sivelestat,and PQ+AH_(2)QDS.The PQ+sivelestat group served as the positive control group.The model of poisoning was established via intragastric treatment with a 20%PQ pesticide solution at 200 mg/kg.Two hours after poisoning,the PQ+sivelestat group was treated with sivelestat,while the PQ+AH_(2)QDS group was given AH_(2)QDS.Six rats were selected from each group on the first,third,and seventh days after poisoning and dissected after anesthesia.The PQ content of the kidneys was measured using the sodium disulfite method.Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes.Apelin expression in the renal tissues was detected using immunofluorescence.Western blotting was used to detect the expression levels of the following proteins in the kidney tissues:IL-6,TNF-α,apelin-APJ(the apelin-angiotensin receptor),NF-κB p65,caspase-1,caspase-8,glucose-regulated protein 78(GRP78),and the C/EBP homologous protein(CHOP).In in vitro study,a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ.Twenty-four hours after poisoning,sivelestat and AH_(2)QDS were administered.The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe.Results:The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH_(2)QDS group.Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group.Vacuolar degeneration of the renal tubule epithelial cells,deposition of crescent-like red staining material in renal follicles,infiltration by a few inflammatory cells,and a small number of cast formation were also observed.However,these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH_(2)QDS group(P<0.05).On the third day after poisoning,immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH_(2)QDS group than in the PQ group.Western blotting analysis results showed that IL-6,TNF-α,NF-κB p65,caspase-1,caspase-8,GRP78,and CHOP protein levels in the PQ group were higher than in the PQ+AH_(2)QDS group(P<0.05).The expression of apelin-APJ proteins in the PQ+AH_(2)QDS group was higher than in the PQ+sivelestat and PQ groups(P<0.05);this difference was significant on Day 3 and Day 7.The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH_(2)QDS group and the PQ+sivelestat group was significantly lower than in the PQ group(P<0.05).Conclusions:This study confirms that AH_(2)QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat.The mechanism of the protective effects of AH_(2)QDS may be linked to reduction in cellular oxidative stress,PQ content of renal tissue,inflammatory injury,endoplasmic reticulum stress,and apoptosis.AH_(2)QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.展开更多
目的探讨百草枯中毒后机体蛋白质表达变化及受影响的信号通路。方法采用同位素标记相对和绝对定量技术检测百草枯中毒大鼠肺组织中差异表达蛋白,对差异表达蛋白进行基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书...目的探讨百草枯中毒后机体蛋白质表达变化及受影响的信号通路。方法采用同位素标记相对和绝对定量技术检测百草枯中毒大鼠肺组织中差异表达蛋白,对差异表达蛋白进行基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析。结果百草枯中毒大鼠肺组织中发现84种差异蛋白,其中48种上调,36种下调。在百草枯中毒早期,差异蛋白主要存在于细胞外区域,主要涉及代谢和应激,补体和凝血级联通路、2-氧代羧酸代谢途径、神经活性配体-受体相互作用途径和金黄色葡萄球菌感染途径4条信号通路受到明显影响。结论差异蛋白和信号转导通路在百草枯致肺损伤早期即可产生变化,可能与炎症损伤和肺纤维化有关。展开更多
文摘Rationale:Multi-organ failure is a symptom of paraquat poisoning,resulting in high mortality and morbidity rates.Though paraquat is widely available,poisoning through inhalation is rare.Patient’s Concern:A 37-year-old male reported to the emergency department with complaints of vomiting after an alleged history of inhalation of paraquat while at work.Diagnosis:Paraquat poisoning.Interventions:Supportive management along with multiple sessions of hemodialysis.Outcomes:Renal complications caused by paraquat were improved after multiple sessions of hemodialysis.However,the patient developed respiratory complications and later due to persistent hypoxemia and non-responsive to supportive therapy,he succumbed to his illness.Lessons:Acute kidney injury is a complication of paraquat poisoning.However,kidney involvement with the inhalational mode is rare.It is caused by reduction and oxidation cycles,as well as the formation of reactive oxygen species,necessitating hemodialysis as the treatment.Without a clear history,a specific clinical trait,or a diagnostic test,diagnosis can be difficult.Our case thus highlights the inhaled paraquat poisoning,presenting with acute kidney injury with late respiratory impairment as a consequence.
文摘Paraquat (PQ, methyl viologen) was widely used in agricultural production throughout the world in 1962 for its efficient herbicidal activity. PQ was also highly toxic drug. About 5 mL medicine including 20% paraquat was life-threatening that can cause poisoning. In 1966, some people died because of PQ poisoning. Most patients had acute respiratory distress syndrome after 2 wk, and 70% of them died due to the lack of effective detoxification drugs. Thus, it was particularly important to understand the pathogenesis of PQ poisoning and give some effective treatments. This article will review the toxicological mechanism and treatment on PQ poisoning of acute lung injury.
文摘BACKGROUND There is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication(APP).AIM To optimize a predictive scoring system for mortality in children with APP.METHODS A total of 113 children with APP from January 1,2010 to January 1,2020 were enrolled in this study.These patients were divided into survivors and nonsurvivors.We compared the clinical characteristics between the two groups and analyzed the independent prognostic risk factors.The survival rates of patients with different values of the pediatric critical illness score(PCIS)were assessed using kaplan-meier survival analysis.The best scoring system was established by using the area under the receiver operating characteristic curve analysis.RESULTS The overall mortality rate was 23.4%.All non-survivors died within 20 days;48.1%(13/27)died within 3 days,and 70.3%(19/27)died within 7 days.Compared to survivors,the non-survivors were older,had higher white blood cell count,alanine aminotransferase(ALT),aspartate aminotransferase,serum creatinine,blood urea nitrogen,glucose,and pediatric early warning score,and had lower platelet count,albumin,Serum sodium(Na+)and PCIS.ALT and PCIS were the independent prognostic risk factors for children with APP.The survival rate of children classified as extremely critical patients(100%)was lower than that of children classified as critical(60%)or noncritical(6.7%)patients.The specificity of ALT was high(96.51%),but the sensitivity was low(59.26%).The sensitivity and specificity of ALT combined with PCIS were high,92.59%and 87.21%,respectively.The difference in mortality was significantly higher for ALT combined with PCIS(area under the receiver operating characteristic:0.937;95%CI:0.875-0.974;P<0.05).CONCLUSION In our study,ALT and PCIS were independent prognostic risk factors for children with APP.ALT combined with PCIS is an optimal predictive mortality scoring system for children with APP.
文摘Objective: To investigate the effects of hemoperfusion combined with hemodialysis on target organ damage in patients with acute paraquat poisoning. Methods: A total of 42 patients with acute paraquat poisoning who were admitted and treated in our hospital between December 2013 and October 2017 were selected as the research subjects, and their therapies were reviewed and used to divide them into the control group (n=20) who received hemoperfusion alone and the combined treatment group (n=22) who received hemoperfusion combined with hemodialysis. The differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were compared between the two groups of patients immediately after admission, after 1 d of treatment and after 3 d of treatment. Results: Immediately after admission, the differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were not statistically significant between the two groups. After 1d of treatment and after 3 d of treatment, kidney function indexes Scr, BUN and β2-MG levels in peripheral blood of combined treatment group were lower than those of control group at corresponding time points respectively;liver function indexes ALT, AST, TB and ALP levels in peripheral blood were lower than those of control group at corresponding time points respectively;lung function indexes PaO2, BE and PCO3- levels in arterial blood were higher than those of control group at corresponding time points respectively whereas PaCO2 levels were lower than those of control group at corresponding time points respectively. Conclusion: Compared with hemoperfusion alone, hemoperfusion combined with hemodialysis is more advantageous in protecting the functions of liver, kidney, lungs and other target organs of patients with acute paraquat poisoning.
基金Natural Science Found of Jiangsu Province(BK20171500,16KJB320003)Program for Key disease of Jiangsu Province Science and Technology Department(BL2014088)+1 种基金Program for Innovative Medical Research Team of Jiangsu Province(CXTDA2017007)Jiangsu Province’s key provincial talents program(QNRC2016597).
文摘BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.
文摘BACKGROUND: Paraquat (PQ) is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 (HSP70) in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS: Seventy-two adult healthy SD rats were randomly divided into a control group (group A, n=24), a poisoning group (group B, n=24), and an ulinastatin group (group C, n=24). The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS: Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi? cantly at all intervals (P〈0.05). The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in? ltration and local hemorrhage, whereas those of group C were signi? cantly lessened.CONCLUSION: Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.
文摘AIM To report our experience of acute kidney injury(AKI) developed after exposure to poisonous substance.METHODS Retrospective study where data was collected from case records of patients coming to this institute during January 1990 to May 2016.This institution is a tertiary care center for renal care in the metropolitan city of Karachi,Pakistan.History of ingested substance,symptoms on presentation,basic laboratory tests on arrival,mode of treatment and outcome were recorded from all patients and are presented here.Patients developing AKI after snake envenomation or scorpion stings are not included in this study.RESULTS During studied period 184 cases of AKI developing after poisoning were seen at our institution.The largest group was from paraphenyline diamine poisoning comprising 135 patients,followed by methanol in 8,organophosphorus compounds in 5,paraquat in 5,copper sulphate in 5,tartaric acid in 4,phenobarbitone in 3 and benzodiazipines,datura,rat killer,fish gall bladder,arsenic,boiler water,ammonium dichromate,acetic acid and herbs with lesser frequency.In 8 patients multiple substances were ingested in combination.Renal replacement therapy was required in 96% of patients.Complete recovery was seen in 72.28% patients,20% died during acute phase of illness.CONCLUSION It is important to report poisonous substances causing vital organ failure to increase awareness among general population as well as health care providers.
基金National Natural Science Foundation of China(No.81960351)Social Development Key Project of Hainan Province(No.ZDYF2019125)Hainan Provincial Natural Science Foundation of China(820QN398)Hainan Province Clinical Medical Center.
文摘Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ pathway.Methods:Male Sprague Dawley rats were divided into four experimental groups:control,PQ,PQ+sivelestat,and PQ+AH_(2)QDS.The PQ+sivelestat group served as the positive control group.The model of poisoning was established via intragastric treatment with a 20%PQ pesticide solution at 200 mg/kg.Two hours after poisoning,the PQ+sivelestat group was treated with sivelestat,while the PQ+AH_(2)QDS group was given AH_(2)QDS.Six rats were selected from each group on the first,third,and seventh days after poisoning and dissected after anesthesia.The PQ content of the kidneys was measured using the sodium disulfite method.Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes.Apelin expression in the renal tissues was detected using immunofluorescence.Western blotting was used to detect the expression levels of the following proteins in the kidney tissues:IL-6,TNF-α,apelin-APJ(the apelin-angiotensin receptor),NF-κB p65,caspase-1,caspase-8,glucose-regulated protein 78(GRP78),and the C/EBP homologous protein(CHOP).In in vitro study,a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ.Twenty-four hours after poisoning,sivelestat and AH_(2)QDS were administered.The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe.Results:The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH_(2)QDS group.Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group.Vacuolar degeneration of the renal tubule epithelial cells,deposition of crescent-like red staining material in renal follicles,infiltration by a few inflammatory cells,and a small number of cast formation were also observed.However,these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH_(2)QDS group(P<0.05).On the third day after poisoning,immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH_(2)QDS group than in the PQ group.Western blotting analysis results showed that IL-6,TNF-α,NF-κB p65,caspase-1,caspase-8,GRP78,and CHOP protein levels in the PQ group were higher than in the PQ+AH_(2)QDS group(P<0.05).The expression of apelin-APJ proteins in the PQ+AH_(2)QDS group was higher than in the PQ+sivelestat and PQ groups(P<0.05);this difference was significant on Day 3 and Day 7.The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH_(2)QDS group and the PQ+sivelestat group was significantly lower than in the PQ group(P<0.05).Conclusions:This study confirms that AH_(2)QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat.The mechanism of the protective effects of AH_(2)QDS may be linked to reduction in cellular oxidative stress,PQ content of renal tissue,inflammatory injury,endoplasmic reticulum stress,and apoptosis.AH_(2)QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.
文摘目的探讨百草枯中毒后机体蛋白质表达变化及受影响的信号通路。方法采用同位素标记相对和绝对定量技术检测百草枯中毒大鼠肺组织中差异表达蛋白,对差异表达蛋白进行基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析。结果百草枯中毒大鼠肺组织中发现84种差异蛋白,其中48种上调,36种下调。在百草枯中毒早期,差异蛋白主要存在于细胞外区域,主要涉及代谢和应激,补体和凝血级联通路、2-氧代羧酸代谢途径、神经活性配体-受体相互作用途径和金黄色葡萄球菌感染途径4条信号通路受到明显影响。结论差异蛋白和信号转导通路在百草枯致肺损伤早期即可产生变化,可能与炎症损伤和肺纤维化有关。