To approach the mechanism of lipopolysaccharide (LPS) in causing acute lung injury (ALI) and the protective effect of rhubarb and dexamethasone, lung specimens were examined with macroscopy, microscopy, electron micro...To approach the mechanism of lipopolysaccharide (LPS) in causing acute lung injury (ALI) and the protective effect of rhubarb and dexamethasone, lung specimens were examined with macroscopy, microscopy, electron microscopy and the biological markers of ALI including lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary capillary permeability and pulmonary alveolar permeability index were observed. The mechanism of the ALI is mainly due to direct injury of alveolar epithelium and pulmonary vascular endothelium. Rhubarb and dexamethasone could significantly reduce the edema of the lung tissue, decrease the red blood cell exudation, neutrophil infiltration and plasma protein exudation in the alveoli and all the biological markers in comparison with the ALI model rats, indicating they have protective action on vascular endothelium and alveolar epithelium.展开更多
This study is to explore the actions of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) on endotoxin (lipopolysaccharide, LPS) induced rat acute lung injury (ALI) and effect of Rhubarb on them. LPS wa... This study is to explore the actions of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) on endotoxin (lipopolysaccharide, LPS) induced rat acute lung injury (ALI) and effect of Rhubarb on them. LPS was injected into the sublingual vein of male Wistar rats to prepare ALI animal models. The rats were divided into 4 groups: LPS, control, Rhubarb, and dexamethasone. Macroscopic and histopathological examinations of the lung specimens were performed and the biological indexes of lung, including wet weight/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability were observed. In the mean time, the contents of serum NO and the activities of lung tissue homogenate iNOS were measured. The results showed that in the LPS group, the injury and celluar infiltration in the pulmonary stroma and alveoli were more prominent than that in the control group. Lung wet weight/dry weight, the rate of neutrophils, protein content, pulmonary alveolar permeability, pulmonary vascular permeability were significantly increased (P<0.01); NO and iNOS were also markedly elevated (P<0.01). In the groups of dexamethasone and Rhubarb, the histopathological changes were significantly milder, and all the above biological indexes of lung injury and the contents of NO and the activities of iNOS were correspondingly decreased (P<0.05). The above data demonstrate that NO and the activities of iNOS play an important role in the onset of ALI; dexamethasone and Rhubarb interfering treatment can ameliorate lung injury and decrease the concentrations of NO and iNOS, showing that through inhibiting the levels of NO and the activities of iNOS, these 2 agents exert protective effect on ALI induced LPS. 展开更多
AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley r...AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.展开更多
AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signal...AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signaling in the gut is important in the control of normal bowel motor function,we aimed to investigate whether the NK1R-mediated bowel motor function was altered in IBS, using a rat IBS model that was previously reported to show colonic dysmotility in response to restraint stress.METHODS: IBS symptoms were produced in male SpragueDawley rats by inducing colitis with acetic acid. Rats were left to recover from colitis for 6 d, and used for experiments 7 d post-induction of colitis. Motor activities of distal colon were recorded in vitro.RESULTS: The contractile sensitivity of isolated colon to a NK1R agonist [Sar9, Met(O2)11]-substance P (1-30 nmol/L)was higher in IBS rats than that in normal rats. After the enteric neurotransmission was blocked by tetrodotoxin (TTX, 1 μmol/L), the contractile sensitivity to the NK1R agonist was increased in normal colon but not in IBS rat colon. The NK1R agonist-induced contraction was not different between the two groups when the agonist was challenged to the TTX-treated colon or the isolated colonic myocytes. A nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) augmented the NK1R agonist-induced contraction only in normal rat colon.CONCLUSION: These results suggest that the NK1R-meidated colonic motor response is increased in IBS rats, due to the decrease in the nitrergic inhibitory neural component.展开更多
Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http:/...Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http://www.who.int/emergencies/mers-cov/en/). MERS-CoV causes an acute and severe respiratory illness with a high mortality rate(~35%) in humans (Shi et al., 2017, Zaki et al., 2012).Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease (Agrawal et al., 2016, Ying et al., 2014).展开更多
OBJECTIVE: To quantitatively evaluate the therapeutic effects of Red Liriope platyphylla(RLP) on atopic dermatitis(AD), alterations in the luciferase(Luc) signal and general phenotype biomarkers were compared in phtha...OBJECTIVE: To quantitatively evaluate the therapeutic effects of Red Liriope platyphylla(RLP) on atopic dermatitis(AD), alterations in the luciferase(Luc) signal and general phenotype biomarkers were compared in phthalic anhydride(PA) treated Interleukin-4(IL-4)/Luc/Consensus non-coding sequence-1(CNS-1) transgenic(Tg) mice following treatment with aqueous extract of RLP(AEt RLP) for4 weeks.METHODS: Alterations in AD phenotypes were measured in IL-4/Luc/CNS-1 Tg mice following treatment with AEt RLP using inflammation parameter analysis, bioluminescence imaging analysis, histological analysis, reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay and Western blot analysis.RESULTS: RLP contained high concentrations of total phenolic compounds, total flavonoid compounds and 5-HNE related to AD therapy. The Luc signal was only detected in the abdominal region and the submandibular lymph node(SL), mesenteric lymph node(ML), thymus and pancreas of the PA treated group. This signal was significantly decreased by 28%-73% throughout the body and in the four organs in PA + AEt RLP treated group. Furthermore, the lymph node weight, immunoglobulin E concentration and dermal thickness were decreased by 37%-67% in the PA + AEt RLP treated group.CONCLUSION: Our findings suggest that the therapeutic effect of AEt RLP on PA induced AD could be successfully quantified by comparison of Luc signals and AD phenotype markers in IL-4/Luc/CNS-1Tg mice, and that the Luc signal was as sensitive as the general AD phenotypes, enabling detection of effects without euthanasia.展开更多
文摘To approach the mechanism of lipopolysaccharide (LPS) in causing acute lung injury (ALI) and the protective effect of rhubarb and dexamethasone, lung specimens were examined with macroscopy, microscopy, electron microscopy and the biological markers of ALI including lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary capillary permeability and pulmonary alveolar permeability index were observed. The mechanism of the ALI is mainly due to direct injury of alveolar epithelium and pulmonary vascular endothelium. Rhubarb and dexamethasone could significantly reduce the edema of the lung tissue, decrease the red blood cell exudation, neutrophil infiltration and plasma protein exudation in the alveoli and all the biological markers in comparison with the ALI model rats, indicating they have protective action on vascular endothelium and alveolar epithelium.
文摘 This study is to explore the actions of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) on endotoxin (lipopolysaccharide, LPS) induced rat acute lung injury (ALI) and effect of Rhubarb on them. LPS was injected into the sublingual vein of male Wistar rats to prepare ALI animal models. The rats were divided into 4 groups: LPS, control, Rhubarb, and dexamethasone. Macroscopic and histopathological examinations of the lung specimens were performed and the biological indexes of lung, including wet weight/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability were observed. In the mean time, the contents of serum NO and the activities of lung tissue homogenate iNOS were measured. The results showed that in the LPS group, the injury and celluar infiltration in the pulmonary stroma and alveoli were more prominent than that in the control group. Lung wet weight/dry weight, the rate of neutrophils, protein content, pulmonary alveolar permeability, pulmonary vascular permeability were significantly increased (P<0.01); NO and iNOS were also markedly elevated (P<0.01). In the groups of dexamethasone and Rhubarb, the histopathological changes were significantly milder, and all the above biological indexes of lung injury and the contents of NO and the activities of iNOS were correspondingly decreased (P<0.05). The above data demonstrate that NO and the activities of iNOS play an important role in the onset of ALI; dexamethasone and Rhubarb interfering treatment can ameliorate lung injury and decrease the concentrations of NO and iNOS, showing that through inhibiting the levels of NO and the activities of iNOS, these 2 agents exert protective effect on ALI induced LPS.
文摘AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.
文摘AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signaling in the gut is important in the control of normal bowel motor function,we aimed to investigate whether the NK1R-mediated bowel motor function was altered in IBS, using a rat IBS model that was previously reported to show colonic dysmotility in response to restraint stress.METHODS: IBS symptoms were produced in male SpragueDawley rats by inducing colitis with acetic acid. Rats were left to recover from colitis for 6 d, and used for experiments 7 d post-induction of colitis. Motor activities of distal colon were recorded in vitro.RESULTS: The contractile sensitivity of isolated colon to a NK1R agonist [Sar9, Met(O2)11]-substance P (1-30 nmol/L)was higher in IBS rats than that in normal rats. After the enteric neurotransmission was blocked by tetrodotoxin (TTX, 1 μmol/L), the contractile sensitivity to the NK1R agonist was increased in normal colon but not in IBS rat colon. The NK1R agonist-induced contraction was not different between the two groups when the agonist was challenged to the TTX-treated colon or the isolated colonic myocytes. A nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) augmented the NK1R agonist-induced contraction only in normal rat colon.CONCLUSION: These results suggest that the NK1R-meidated colonic motor response is increased in IBS rats, due to the decrease in the nitrergic inhibitory neural component.
基金supported by the National Key Research and Development Program of China (2016YFD0500300 to Wenjie Tan)
文摘Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http://www.who.int/emergencies/mers-cov/en/). MERS-CoV causes an acute and severe respiratory illness with a high mortality rate(~35%) in humans (Shi et al., 2017, Zaki et al., 2012).Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease (Agrawal et al., 2016, Ying et al., 2014).
基金supported by grants to Dr. Dae Youn Hwang from the Korea Institute of Planning Evaluation for Technology of Food, Agriculture, Forestry and Fisheries (116027-032-HD030)
文摘OBJECTIVE: To quantitatively evaluate the therapeutic effects of Red Liriope platyphylla(RLP) on atopic dermatitis(AD), alterations in the luciferase(Luc) signal and general phenotype biomarkers were compared in phthalic anhydride(PA) treated Interleukin-4(IL-4)/Luc/Consensus non-coding sequence-1(CNS-1) transgenic(Tg) mice following treatment with aqueous extract of RLP(AEt RLP) for4 weeks.METHODS: Alterations in AD phenotypes were measured in IL-4/Luc/CNS-1 Tg mice following treatment with AEt RLP using inflammation parameter analysis, bioluminescence imaging analysis, histological analysis, reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay and Western blot analysis.RESULTS: RLP contained high concentrations of total phenolic compounds, total flavonoid compounds and 5-HNE related to AD therapy. The Luc signal was only detected in the abdominal region and the submandibular lymph node(SL), mesenteric lymph node(ML), thymus and pancreas of the PA treated group. This signal was significantly decreased by 28%-73% throughout the body and in the four organs in PA + AEt RLP treated group. Furthermore, the lymph node weight, immunoglobulin E concentration and dermal thickness were decreased by 37%-67% in the PA + AEt RLP treated group.CONCLUSION: Our findings suggest that the therapeutic effect of AEt RLP on PA induced AD could be successfully quantified by comparison of Luc signals and AD phenotype markers in IL-4/Luc/CNS-1Tg mice, and that the Luc signal was as sensitive as the general AD phenotypes, enabling detection of effects without euthanasia.