BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acu...BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute pancreatitis.AIM To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute pan-creatitis.METHODS The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)groups.Relevant data was collected for each group.Western blot analysis assessed PLD2 protein expression in patient serum.Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration.Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay.Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration.RESULTS Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumor necrosis factor-α,interleukin-1β,and interleukin-6 in the severe group were higher than those in the moderate and mild groups(P<0.05),and the levels in the moderate group were also higher than those in the mild group(P<0.05).The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups(P<0.05),and the moderate group was also higher than the mild group(P<0.05).In addition,the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group(P<0.05),and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group(P<0.05).The number of migrating neutrophils in the severe group+PLD2 inhibitor group was significantly higher than that in the severe group(P<0.05),indicating that PLD2 inhibitors significantly stimulated neutrophil migration.CONCLUSION PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis.Its protein expression varied among patients based on the severity of the disease,and a negative correlation existed between PLD2 expression and disease severity.Additionally,PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.展开更多
BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes p...BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.展开更多
Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in ...Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.展开更多
The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits we...The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.展开更多
AIM:To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were random...AIM:To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 and 0.35±0.05) mL/(min·g) was significantly lower than that in control group (0.86±0.11 and 0.85±0.06) mL/(min·g) (P<0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and 0.50±0.06) mlV(min·g) was significantly lower than that in control group (1.56±0.18 and 1.61±0.11) mL/(min·g) (P<0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20)μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07)μg/L (P<0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P<0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.展开更多
AIM: To study the effect of bromophenacyl bromide (BPB), a phospholipase A2 inhibitor on gastric secretion and to protect chemically induced gastric and duodenal ulcers in rats. METHODS: Acid secretion studies were un...AIM: To study the effect of bromophenacyl bromide (BPB), a phospholipase A2 inhibitor on gastric secretion and to protect chemically induced gastric and duodenal ulcers in rats. METHODS: Acid secretion studies were undertaken in pylorus-ligated rats with BPB treatment (0, 5, 15 and 45 mg/kg). Gastric and duodenal lesions in the rats were induced by ethanol and cysteamine respectively. The levels of gastric wall mucus, nonprotein sulfhydryls (NP- SH) and myeloperoxidase (MPO) were also measured in the glandular stomach of rats following ethanol induced gastric lesions. RESULTS: BPB produced a dose-dependent inhibition of gastric acid secretion and acidity in rats. Pretreatment with BPB significantly attenuated the formation of etha- nol induced gastric lesion. BPB also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of BPB was associated with signifi- cant inhibition of ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. These findings pointed towards the mediation of sulfhydryls in BPB induced gas- trointestinal cytoprotection. CONCLUSION: BPB possesses significant antiulcer and cytoprotective activity against experimentally induced gastroduodenal lesions.展开更多
Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for is...Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.展开更多
Acute fulminant pancreatitis was produced in dogs by injection of autobile into the main pancreatic duct.After injection the phospholipase A_2(PLA_2)activities in serum,lung lymph and bronchoalveolar lavage fluid(BAL)...Acute fulminant pancreatitis was produced in dogs by injection of autobile into the main pancreatic duct.After injection the phospholipase A_2(PLA_2)activities in serum,lung lymph and bronchoalveolar lavage fluid(BAL)were elevated significantly,lung lymph flow and pulmonary transvascular potein clearance increased progressively,protein content and cell numbers in BAL in the experimental animals were significantly higher than those in the control animals.Furthermore the lung index,wet to dry lung weight ratio,extravascular lung water to bloodless dry lung weight ra- tio,extravascuar lung water to bloodless dry lung weight ratio increased significantly as compared to control animals.Pretreatment with PLA_2 inhibitor,chloroquine,blocked the changes mentioned above.This experiment suggests:1.PLA_2 activity in lung lymph fluid as well as in serum and BAL is elevated in acute hemorrhagic pancreatitis.2.Elevated PLA_2 activity may increase the pulmonary vascular permeability.3.PLA_2 is the major factor leading to pulmonary edema in acute hemorrhagic pancreatitis.4.Phagocytes contribute to the lung injury induced by PLA_2 to some ex- tent.展开更多
A murine maorophage-like cell line, J774, acquri ed, in response to LPS, an ability to kill tumor necrosis factor (TNF)-insensitive target P815 mastocytoma cells, whereas another cell line, P388D1, did not. LPS-trigge...A murine maorophage-like cell line, J774, acquri ed, in response to LPS, an ability to kill tumor necrosis factor (TNF)-insensitive target P815 mastocytoma cells, whereas another cell line, P388D1, did not. LPS-triggered signaling mechanisms between the two cell lines were compared with an aim to inquire about the possible nature of the above-mentioned difference. The results showed that two cell lines respond to LPS-treatment by parallel activation of both phospholipases C and A2 (PLC and PLA2) to approximately the same extent. The maximum response of both enzymes of J774 cells was noted within 10 min of the treatment, whereas that of P388D1 cells required more than 20 min. The other properties of LPS-responsive enzymes studied were similar between two cell lines, includingAotivation of PLC and PLA2 and PKC in macrophages by LPSGa2+ augmentation of enzyme activation, participation of guanine nuoleotide binding (G) proteins in the initial activation processes, and inhibition of enzyme activation by the prior treatment of cells with cholera or pertussis toxins etc. Moreover, LPS-triggered activation of PLC and PLA2 was found to be followed by the increase of PKC activities in both cell lines. In spite of these similarities, J774 cells possessed both basic and acidic forms of PKC activities, while P 388D1 cells owned only PKC of basic form. Nevertheless, the question why J774 cells, but not P388D1 cells, can acquire the tumorioidal activity, aganist P815 cells following LPS-treatment remains to be answered.展开更多
Objective To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2)inhibitor-HyPE(linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid)on human bone marrow endothel...Objective To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2)inhibitor-HyPE(linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid)on human bone marrow endothelial cell line(HBME-1). Methods In order to examine the suppressing effects of HyPE on HBME-1 proliferation, migration, and capillary-like tube formation, HBME-1 were activated by angiogenic factor, specifically by basic fibroblast growth factor(b-FGF), vascular endothelial growth factor(VEGF),and oncostatin M(OSM)(at a final concentration of 25, 20, and 2.5 ng/mL, respectively), then HBME-1 proliferation, migration, and tube forma-tion were studied in the absence or presence of HyPE. HBME-1 tube formation was specially analyzed in fibrin gel. Results HyPE effectively inhibited HBME-1 proliferation and migration as a dose-dependent manner, whatever HBME-1 were grown in the control culture medium or stimulated with b-FGF, VEGF, or OSM. In fibrin, the formations of HBME-1 derived tube-like structures were enhanced by all angiogenic factors, but these were strongly suppressed by HyPE. Conclusions The results support the involvement of sPLA2 in angiogenesis. It is proposed that sPLA2 inhibitor introduces a novel approach in the control of cancer development.展开更多
文摘BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute pancreatitis.AIM To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute pan-creatitis.METHODS The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)groups.Relevant data was collected for each group.Western blot analysis assessed PLD2 protein expression in patient serum.Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration.Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay.Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration.RESULTS Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumor necrosis factor-α,interleukin-1β,and interleukin-6 in the severe group were higher than those in the moderate and mild groups(P<0.05),and the levels in the moderate group were also higher than those in the mild group(P<0.05).The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups(P<0.05),and the moderate group was also higher than the mild group(P<0.05).In addition,the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group(P<0.05),and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group(P<0.05).The number of migrating neutrophils in the severe group+PLD2 inhibitor group was significantly higher than that in the severe group(P<0.05),indicating that PLD2 inhibitors significantly stimulated neutrophil migration.CONCLUSION PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis.Its protein expression varied among patients based on the severity of the disease,and a negative correlation existed between PLD2 expression and disease severity.Additionally,PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.
基金Supported by the Key Specialty Construction Project of Shanghai Pudong New Area Health Commission,No.PWZzk2022-17Shanghai East Hospital Clinical Research Project,No.DFLC2022019and the Featured Clinical Discipline Project of Shanghai Pudong District,No.PWYts2021-06.
文摘BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.
文摘Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.
文摘The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.
基金Supported by the Traditional Chinese Medicine Administration Bureau Foundation of Jiangsu Province,No.9965the Applied Basic Research Program of Science and Technology Commission Foundation of Jiangsu Province,No.BJ2000327
文摘AIM:To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 and 0.35±0.05) mL/(min·g) was significantly lower than that in control group (0.86±0.11 and 0.85±0.06) mL/(min·g) (P<0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and 0.50±0.06) mlV(min·g) was significantly lower than that in control group (1.56±0.18 and 1.61±0.11) mL/(min·g) (P<0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20)μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07)μg/L (P<0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P<0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.
文摘AIM: To study the effect of bromophenacyl bromide (BPB), a phospholipase A2 inhibitor on gastric secretion and to protect chemically induced gastric and duodenal ulcers in rats. METHODS: Acid secretion studies were undertaken in pylorus-ligated rats with BPB treatment (0, 5, 15 and 45 mg/kg). Gastric and duodenal lesions in the rats were induced by ethanol and cysteamine respectively. The levels of gastric wall mucus, nonprotein sulfhydryls (NP- SH) and myeloperoxidase (MPO) were also measured in the glandular stomach of rats following ethanol induced gastric lesions. RESULTS: BPB produced a dose-dependent inhibition of gastric acid secretion and acidity in rats. Pretreatment with BPB significantly attenuated the formation of etha- nol induced gastric lesion. BPB also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of BPB was associated with signifi- cant inhibition of ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. These findings pointed towards the mediation of sulfhydryls in BPB induced gas- trointestinal cytoprotection. CONCLUSION: BPB possesses significant antiulcer and cytoprotective activity against experimentally induced gastroduodenal lesions.
文摘Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.
文摘Acute fulminant pancreatitis was produced in dogs by injection of autobile into the main pancreatic duct.After injection the phospholipase A_2(PLA_2)activities in serum,lung lymph and bronchoalveolar lavage fluid(BAL)were elevated significantly,lung lymph flow and pulmonary transvascular potein clearance increased progressively,protein content and cell numbers in BAL in the experimental animals were significantly higher than those in the control animals.Furthermore the lung index,wet to dry lung weight ratio,extravascular lung water to bloodless dry lung weight ra- tio,extravascuar lung water to bloodless dry lung weight ratio increased significantly as compared to control animals.Pretreatment with PLA_2 inhibitor,chloroquine,blocked the changes mentioned above.This experiment suggests:1.PLA_2 activity in lung lymph fluid as well as in serum and BAL is elevated in acute hemorrhagic pancreatitis.2.Elevated PLA_2 activity may increase the pulmonary vascular permeability.3.PLA_2 is the major factor leading to pulmonary edema in acute hemorrhagic pancreatitis.4.Phagocytes contribute to the lung injury induced by PLA_2 to some ex- tent.
基金This work was supportod in part by grants (CA35977 and AL 22742)form the National institute of cancer and the national instituty of allerge and infections disease ,and by a grant form wesley foundation ,wichita ,kansas
文摘A murine maorophage-like cell line, J774, acquri ed, in response to LPS, an ability to kill tumor necrosis factor (TNF)-insensitive target P815 mastocytoma cells, whereas another cell line, P388D1, did not. LPS-triggered signaling mechanisms between the two cell lines were compared with an aim to inquire about the possible nature of the above-mentioned difference. The results showed that two cell lines respond to LPS-treatment by parallel activation of both phospholipases C and A2 (PLC and PLA2) to approximately the same extent. The maximum response of both enzymes of J774 cells was noted within 10 min of the treatment, whereas that of P388D1 cells required more than 20 min. The other properties of LPS-responsive enzymes studied were similar between two cell lines, includingAotivation of PLC and PLA2 and PKC in macrophages by LPSGa2+ augmentation of enzyme activation, participation of guanine nuoleotide binding (G) proteins in the initial activation processes, and inhibition of enzyme activation by the prior treatment of cells with cholera or pertussis toxins etc. Moreover, LPS-triggered activation of PLC and PLA2 was found to be followed by the increase of PKC activities in both cell lines. In spite of these similarities, J774 cells possessed both basic and acidic forms of PKC activities, while P 388D1 cells owned only PKC of basic form. Nevertheless, the question why J774 cells, but not P388D1 cells, can acquire the tumorioidal activity, aganist P815 cells following LPS-treatment remains to be answered.
文摘Objective To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2)inhibitor-HyPE(linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid)on human bone marrow endothelial cell line(HBME-1). Methods In order to examine the suppressing effects of HyPE on HBME-1 proliferation, migration, and capillary-like tube formation, HBME-1 were activated by angiogenic factor, specifically by basic fibroblast growth factor(b-FGF), vascular endothelial growth factor(VEGF),and oncostatin M(OSM)(at a final concentration of 25, 20, and 2.5 ng/mL, respectively), then HBME-1 proliferation, migration, and tube forma-tion were studied in the absence or presence of HyPE. HBME-1 tube formation was specially analyzed in fibrin gel. Results HyPE effectively inhibited HBME-1 proliferation and migration as a dose-dependent manner, whatever HBME-1 were grown in the control culture medium or stimulated with b-FGF, VEGF, or OSM. In fibrin, the formations of HBME-1 derived tube-like structures were enhanced by all angiogenic factors, but these were strongly suppressed by HyPE. Conclusions The results support the involvement of sPLA2 in angiogenesis. It is proposed that sPLA2 inhibitor introduces a novel approach in the control of cancer development.
