Since its discovery nearly thirty years ago, platelet-activating factor has emerged as one of the more important lipidmediators known. Platelet-activating factor (PAF; 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholi...Since its discovery nearly thirty years ago, platelet-activating factor has emerged as one of the more important lipidmediators known. Platelet-activating factor (PAF; 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) exists en-dogenously as a mixture of molecular species with structural variants of the alkyl moiety. PAF is a novel potent signal-ing phospholipid that has unique pleiotropic biological properties in addition to platelet activation. PAF also plays a sig-nificant role in reproduction. PAF content in squirrel monkey sperm is significantly higher during the breeding seasonthan the non-breeding season. PAF content in human sperm has a positive correlation with seminal parameters and preg-nancy outcomes. High-fertility boars have significantly more PAF in their sperm than low-fertility boars. The enzymes(lyso-PAF-acetyltransferase and PAF-acetylhydrolase) necessary for PAF activation and deactivation are present insperm. PAF-acetylhydrolase may act as a 'decapacitation factor'. Removal of this enzyme during capacitation maypromote PAF synthesis increasing motility and fertilization. PAF also plays a significant role in the fertilization process,enhancing the fertilization rates of oocytes. Enhanced embryo development has also been reported in oocytes fertilizedwith PAF-treated sperm. PAF antagonists inhibit sperm motility, acrosome reaction, and fertilization, thus suggestingthe presence of receptors for PAF. The PAF-receptor is present on sperm, with altered transcript levels and distributionpatterns on abnormal cells. Whereas the exact mechanism of PAF in sperm function and reproduction is uncertain, itsimportance in normal fertility is substantial. The reproductive significance of PAF activity in sperm and fertility plus therole of PAF in the establishment of pregnancy requires further study.展开更多
AIM: To determine the effects of BN52021 on platelet-activating factor receptor (PAFR) signaling molecules under lipopolysaccharide (LPS)-induced inflammatory conditions in MS1 cells. METHODS: MS1 cells (a mouse pancr...AIM: To determine the effects of BN52021 on platelet-activating factor receptor (PAFR) signaling molecules under lipopolysaccharide (LPS)-induced inflammatory conditions in MS1 cells. METHODS: MS1 cells (a mouse pancreatic islet endothelial cell line) were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mmol/L glutamine and 100 μg/mL penicillin/streptomycin in 5% CO 2 at 37 ℃. After growth to confluency in media, the cells were processed for subsequent studies. The MS1 cells received 0, 0.1, 1 and 10 μg/mL LPS in this experiment. The viability/prolifera-tion of the cells induced by LPS was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Apoptosis and necrosis of the cells under the inflammatory condition described previously were observed using Hoechst 33342-propidium iodide staining. Adenylate cyclase (AC), phospholipase A 2 (PLA 2 ), phospholipase Cβ (PLCβ), protein tyrosine kinase (PTK), G protein-coupled receptor kinases (GRK) and p38-mitogen-activated protein kinase (p38 MAPK) mRNA in the PAFR signaling pathway were measured by real-time polymerase chain reaction. The protein expression level of phosphorylated AC (p-AC), phosphorylated PLA 2 (p-PLA 2 ), phosphorylated PTK (p-PTK), phosphorylated p38 MAPK (p-p38 MAPK), PLCβ and GRK was measured using Western blotting analysis. RESULTS: The activity of MS1 cells incubated with dif- ferent concentrations of LPS for 6 h decreased significantly in the 1 μg/mL LPS group (0.49 ± 0.10 vs 0.67 ± 0.13, P < 0.05) and 10 μg/mL LPS group (0.44 ± 0.10 vs 0.67 ± 0.13, P < 0.001), but not in 0.1 μg/mL group. When the incubation time was extended to 12 h (0.33 ± 0.05, 0.32 ± 0.03 and 0.25 ± 0.03 vs 0.69 ± 0.01) and 24 h (0.31 ± 0.01, 0.29 ± 0.03 and 0.25 ± 0.01 vs 0.63 ± 0.01), MS1 cell activity decreased in all LPS concentration groups compared with the blank control (P < 0.001). BN52021 significantly improved the cell activity when its concentration reached 50 μmol/L compared with the group that received LPS treatment alone, which was consistent with the results obtained from fluorescence staining. The mRNAs levels of AC (4.02 ± 0.14 vs 1.00 ± 0.13), GRK (2.63 ± 0.03 vs 1.00 ± 0.12), p38 MAPK (3.87 ± 0.07 vs 1.00 ± 0.17), PLA 2 (3.31 ± 0.12 vs 1.00 ± 0.12), PLCβ (2.09 ± 0.08 vs 1.00 ± 0.06) and PTK (1.85 ± 0.07 vs 1.00 ± 0.11) were up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up- regulated mRNAs including AC (2.35 ± 0.13 vs 3.87 ± 0.08), GRK (1.17 ± 0.14 vs 2.65 ± 0.12), p38 MAPK (1.48 ± 0.18 vs 4.30 ± 0.07), PLCβ (1.69 ± 0.10 vs 2.41 ± 0.13) and PLA 2 (1.87 ± 0.11 vs 2.96 ± 0.08)were significantly suppressed by BN52021 except for that of PTK. The level of p-AC (1.11 ± 0.12 vs 0.65 ± 0.08), GRK (0.83 ± 0.07 vs 0.50 ± 0.03), PLCβ (0.83 ± 0.16 vs 0.50 ± 0.10) and p-p38 MAPK (0.74 ± 0.10 vs 0.38 ± 0.05) was up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up-regulated proteins, including p-AC (0.65 ± 0.15 vs 1.06 ± 0.14), GRK (0.47 ± 0.10 vs 0.80 ± 0.06), PLCβ (0.47 ± 0.04 vs 0.80 ± 0.19) and p-p38 MAPK (0.30 ± 0.10 vs 0.97 ± 0.05), was significantly suppressed by BN52021, but p-PLA 2 and p-PTK protein level were not suppressed. CONCLUSION: BN52021 could effectively inhibit LPS-induced inflammation by down-regulating the mRNA and protein levels of AC, GRK, p38 MAPK, PLA 2 and PLCβ in the PAFR signaling pathway.展开更多
OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of ...OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.展开更多
Platelet-activating factor (PAF) exhibits a variety of biological activities and it be thought to involved in various pathophysiological process. In this paper, some studies were summarized about those roles ofPAF in ...Platelet-activating factor (PAF) exhibits a variety of biological activities and it be thought to involved in various pathophysiological process. In this paper, some studies were summarized about those roles ofPAF in a variety productive processes of female of mammalian that inctude fertilization, implantation and parturition, and that was involved in the concentration, synthesis, deiradation and some assay methods of PAF. Therelationship between PAF and early pregnancy factor (EPF) was reviewed.展开更多
The effects of hydrogen peroxide(H<sub>2</sub>O<sub>2</sub>)on endothelial-polymorphonuclear leuko-cyte(EC-PMN)adhesion and their mechanisms were studied in cultured bovine pulmonaryartery ...The effects of hydrogen peroxide(H<sub>2</sub>O<sub>2</sub>)on endothelial-polymorphonuclear leuko-cyte(EC-PMN)adhesion and their mechanisms were studied in cultured bovine pulmonaryartery endothelial monolayers in vitro.H<sub>2</sub>O<sub>2</sub> at various concentrations(10<sup>-3</sup>,10<sup>-2</sup>,10<sup>-1</sup>mol/Lrespectively)stimulated EC-dependent PMN adhesion,of which 10<sup>-2</sup>mol/L H<sub>2</sub>O<sub>2</sub> was the mostpotent one,increasing adhesion to 2.3 times that of the control.Pretreatment of PMNs with SRI63-441,a platelet-activating factor(PAF)receptor antagonist,had no inhibition effect on H<sub>2</sub>O<sub>2</sub>induced EC-PMN adhesion.Pretreatment of ECs with SRI 63-441 before H<sub>2</sub>O<sub>2</sub> exposure signifi-cantly decreased PMN adherence to ECs.Pretreatment of ECs with phospholipase A<sub>2</sub> inhibitorp-bromophenacyl-bromide or calmodulin antagonist chlorpromazine and calcium ion chelate EG-TA obviously decreased H<sub>2</sub>O<sub>2</sub> induced increment of EC-PMN adhesion.These results suggestthat H<sub>2</sub>O<sub>2</sub> may activate ECs,causing the inflow of extracellular calcium or the release of calciumfrom intracellular deposits.Increased intracellar Ca<sup>2+</sup>may bind with calmodulin to activate phos-pholipase A<sub>2</sub>,thus initiating PAF synthesis and promoting EC-PMN adhesion.展开更多
This review described origination, biosynthesis and functions of platelet-activating factor (PAF) in the reproductive system of mammals and human beings. The article mainly focused on biological roles of the phospho...This review described origination, biosynthesis and functions of platelet-activating factor (PAF) in the reproductive system of mammals and human beings. The article mainly focused on biological roles of the phospholipid mediator in sperm fertilization and embryonic implantation. As an autocrine product of sperm and embryos, PAF markedly stimulates sperm motility and fertilization and serves as a capacitation factor in a ligand-receptor manner, After fertilization, embryo-derived PAF improves its own development, especially from fertilized ova to blastocyst stage and is thought to act as an embryo growth factor in the same manner as on sperm. Its mechanism of action was also clarified. At the end, it was presented some advances in its clinical application, followed by discussion of some issues possibly concerning in its current application.展开更多
Objective: To study the serum platelet-activating factor (PAF) level of patients with cerebral infarction from transient ischemic attack (TIA) and its correlation with coagulation function and inflammatory response. M...Objective: To study the serum platelet-activating factor (PAF) level of patients with cerebral infarction from transient ischemic attack (TIA) and its correlation with coagulation function and inflammatory response. Methods: TIA patients who were hospitalized in Neurology Department of Foshan Second People's Hospital between September 2016 and July 2017 were selected and divided into simple TIA group and cerebral infarction group according to the progression into cerebral infarction or not within 1 week;healthy subjects who received physical examination during the same period were selected as the control group. Serum levels of PAF, coagulation function indexes and inflammation indexes were detected. Results: Serum PAF, FVIII, vWF, TNF-α, hs-CRP, MCP-1 and IL-17 contents of cerebral infarction group and simple TIA group were significantly higher than those of control group while PT, APTT and TT levels were significantly shorter than those of control group;serum PAF, FVIII, vWF, TNF-α, hs-CRP, MCP-1 and IL-17 contents of cerebral infarction group were significantly higher than those of simple TIA group while PT, APTT and TT levels were significantly shorter than those of simple TIA group;serum FVIII, vWF, TNF-α, hs-CRP, MCP-1 and IL-17 contents of TIA patients with high PAF content were significantly higher than those of TIA patients with low PAF content while PT, APTT and TT levels were significantly shorter than those of TIA patients with low PAF content. Conclusion: Excessively generated PAF can promote TIA progression to cerebral infarction by activating coagulation pathway and inflammatory response.展开更多
The activity of plasma platelet-activating factor(PAF) from pregnant women before and after delivery was determined. Plasma samples were taken from 74 pregnant women, among whom 24 were normotensive controls, 30 mild ...The activity of plasma platelet-activating factor(PAF) from pregnant women before and after delivery was determined. Plasma samples were taken from 74 pregnant women, among whom 24 were normotensive controls, 30 mild and moderate hypertensive and 20 severe hypertensive. Of the two hypertensive groups(pregnancy-induced hypertension, PIH), PAF activity measured by a bioassay was significantly higher than that of normotensive control at 38 weeks in gestation , indicating a possible role of this potent lipid mediator in the pathophysiological mechanism of PIH. After delivery, PAF activity was obviously increased in all three groups , showing the regulation of placenta in PAF metabolism.展开更多
Objective: To explore the association of the platelet-activating factor receptor(PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease(CHD) and blood stasis syndrome(BSS) of CHD in Chine...Objective: To explore the association of the platelet-activating factor receptor(PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease(CHD) and blood stasis syndrome(BSS) of CHD in Chinese Han population. Methods: A total of 570 CHD patients(299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaP shot technology. The statistical analysis was conducted using a multiple variable logistic regression model. Results: Significant differences were detected in the genotypes frequency distributions of the rs5938(P<0.01), but not the rs313152(P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio(aOR)=0.35, 95% confidence interval(CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD(aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD(aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS(aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS(aOR=1.22, 95% CI: 0.81 to 1.85, P>0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27(95% CI: 0.1 to 0.7, P<0.01). Conclusion: The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.展开更多
“Let’s Move!”is a comprehensive initiative,launched by the First Lady,Michelle Obama,dedicates to solving problems of obesity,which is growing in child.The life behaviors do affect obesity;however,the mechanistic i...“Let’s Move!”is a comprehensive initiative,launched by the First Lady,Michelle Obama,dedicates to solving problems of obesity,which is growing in child.The life behaviors do affect obesity;however,the mechanistic insight in molecular level is still not clear.In this study,by continually monitoring mouse body weight under chow and high fat western diets as well as metabolic,physical activity and food intake behaviors assessed in a CLAMS Comprehensive Lab Animal Monitoring System,we demonstrated that the platelet-activating factor receptor(PTAFR)contributes to modification of life behaviors.PTAFR does not affect metabolism of ingested dietary fat and carbohydrate in young animals;however,Ptafr ablation dramatically increased weight gain without affecting adipose tissue accumulation.Ptafr/mice possess new habits that increased food intake and decreased movement.Our studies suggest that regulation of PTAFR activity may be a novel strategy to control obesity in children or young adults.展开更多
文摘Since its discovery nearly thirty years ago, platelet-activating factor has emerged as one of the more important lipidmediators known. Platelet-activating factor (PAF; 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) exists en-dogenously as a mixture of molecular species with structural variants of the alkyl moiety. PAF is a novel potent signal-ing phospholipid that has unique pleiotropic biological properties in addition to platelet activation. PAF also plays a sig-nificant role in reproduction. PAF content in squirrel monkey sperm is significantly higher during the breeding seasonthan the non-breeding season. PAF content in human sperm has a positive correlation with seminal parameters and preg-nancy outcomes. High-fertility boars have significantly more PAF in their sperm than low-fertility boars. The enzymes(lyso-PAF-acetyltransferase and PAF-acetylhydrolase) necessary for PAF activation and deactivation are present insperm. PAF-acetylhydrolase may act as a 'decapacitation factor'. Removal of this enzyme during capacitation maypromote PAF synthesis increasing motility and fertilization. PAF also plays a significant role in the fertilization process,enhancing the fertilization rates of oocytes. Enhanced embryo development has also been reported in oocytes fertilizedwith PAF-treated sperm. PAF antagonists inhibit sperm motility, acrosome reaction, and fertilization, thus suggestingthe presence of receptors for PAF. The PAF-receptor is present on sperm, with altered transcript levels and distributionpatterns on abnormal cells. Whereas the exact mechanism of PAF in sperm function and reproduction is uncertain, itsimportance in normal fertility is substantial. The reproductive significance of PAF activity in sperm and fertility plus therole of PAF in the establishment of pregnancy requires further study.
基金Supported by The National Natural Science Foundation of China,No.81173393the Natural Science Foundation of Tianjin City,Grant No.12YFJZJC00800+1 种基金the Scientific Research Foundation for PhD grant to Xia SH,No.WYB201010the Innovation Team Program(WHTD201310)from the Logistics University of the Chinese People's Armed Police Force
文摘AIM: To determine the effects of BN52021 on platelet-activating factor receptor (PAFR) signaling molecules under lipopolysaccharide (LPS)-induced inflammatory conditions in MS1 cells. METHODS: MS1 cells (a mouse pancreatic islet endothelial cell line) were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mmol/L glutamine and 100 μg/mL penicillin/streptomycin in 5% CO 2 at 37 ℃. After growth to confluency in media, the cells were processed for subsequent studies. The MS1 cells received 0, 0.1, 1 and 10 μg/mL LPS in this experiment. The viability/prolifera-tion of the cells induced by LPS was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Apoptosis and necrosis of the cells under the inflammatory condition described previously were observed using Hoechst 33342-propidium iodide staining. Adenylate cyclase (AC), phospholipase A 2 (PLA 2 ), phospholipase Cβ (PLCβ), protein tyrosine kinase (PTK), G protein-coupled receptor kinases (GRK) and p38-mitogen-activated protein kinase (p38 MAPK) mRNA in the PAFR signaling pathway were measured by real-time polymerase chain reaction. The protein expression level of phosphorylated AC (p-AC), phosphorylated PLA 2 (p-PLA 2 ), phosphorylated PTK (p-PTK), phosphorylated p38 MAPK (p-p38 MAPK), PLCβ and GRK was measured using Western blotting analysis. RESULTS: The activity of MS1 cells incubated with dif- ferent concentrations of LPS for 6 h decreased significantly in the 1 μg/mL LPS group (0.49 ± 0.10 vs 0.67 ± 0.13, P < 0.05) and 10 μg/mL LPS group (0.44 ± 0.10 vs 0.67 ± 0.13, P < 0.001), but not in 0.1 μg/mL group. When the incubation time was extended to 12 h (0.33 ± 0.05, 0.32 ± 0.03 and 0.25 ± 0.03 vs 0.69 ± 0.01) and 24 h (0.31 ± 0.01, 0.29 ± 0.03 and 0.25 ± 0.01 vs 0.63 ± 0.01), MS1 cell activity decreased in all LPS concentration groups compared with the blank control (P < 0.001). BN52021 significantly improved the cell activity when its concentration reached 50 μmol/L compared with the group that received LPS treatment alone, which was consistent with the results obtained from fluorescence staining. The mRNAs levels of AC (4.02 ± 0.14 vs 1.00 ± 0.13), GRK (2.63 ± 0.03 vs 1.00 ± 0.12), p38 MAPK (3.87 ± 0.07 vs 1.00 ± 0.17), PLA 2 (3.31 ± 0.12 vs 1.00 ± 0.12), PLCβ (2.09 ± 0.08 vs 1.00 ± 0.06) and PTK (1.85 ± 0.07 vs 1.00 ± 0.11) were up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up- regulated mRNAs including AC (2.35 ± 0.13 vs 3.87 ± 0.08), GRK (1.17 ± 0.14 vs 2.65 ± 0.12), p38 MAPK (1.48 ± 0.18 vs 4.30 ± 0.07), PLCβ (1.69 ± 0.10 vs 2.41 ± 0.13) and PLA 2 (1.87 ± 0.11 vs 2.96 ± 0.08)were significantly suppressed by BN52021 except for that of PTK. The level of p-AC (1.11 ± 0.12 vs 0.65 ± 0.08), GRK (0.83 ± 0.07 vs 0.50 ± 0.03), PLCβ (0.83 ± 0.16 vs 0.50 ± 0.10) and p-p38 MAPK (0.74 ± 0.10 vs 0.38 ± 0.05) was up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up-regulated proteins, including p-AC (0.65 ± 0.15 vs 1.06 ± 0.14), GRK (0.47 ± 0.10 vs 0.80 ± 0.06), PLCβ (0.47 ± 0.04 vs 0.80 ± 0.19) and p-p38 MAPK (0.30 ± 0.10 vs 0.97 ± 0.05), was significantly suppressed by BN52021, but p-PLA 2 and p-PTK protein level were not suppressed. CONCLUSION: BN52021 could effectively inhibit LPS-induced inflammation by down-regulating the mRNA and protein levels of AC, GRK, p38 MAPK, PLA 2 and PLCβ in the PAFR signaling pathway.
文摘OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.
文摘Platelet-activating factor (PAF) exhibits a variety of biological activities and it be thought to involved in various pathophysiological process. In this paper, some studies were summarized about those roles ofPAF in a variety productive processes of female of mammalian that inctude fertilization, implantation and parturition, and that was involved in the concentration, synthesis, deiradation and some assay methods of PAF. Therelationship between PAF and early pregnancy factor (EPF) was reviewed.
文摘The effects of hydrogen peroxide(H<sub>2</sub>O<sub>2</sub>)on endothelial-polymorphonuclear leuko-cyte(EC-PMN)adhesion and their mechanisms were studied in cultured bovine pulmonaryartery endothelial monolayers in vitro.H<sub>2</sub>O<sub>2</sub> at various concentrations(10<sup>-3</sup>,10<sup>-2</sup>,10<sup>-1</sup>mol/Lrespectively)stimulated EC-dependent PMN adhesion,of which 10<sup>-2</sup>mol/L H<sub>2</sub>O<sub>2</sub> was the mostpotent one,increasing adhesion to 2.3 times that of the control.Pretreatment of PMNs with SRI63-441,a platelet-activating factor(PAF)receptor antagonist,had no inhibition effect on H<sub>2</sub>O<sub>2</sub>induced EC-PMN adhesion.Pretreatment of ECs with SRI 63-441 before H<sub>2</sub>O<sub>2</sub> exposure signifi-cantly decreased PMN adherence to ECs.Pretreatment of ECs with phospholipase A<sub>2</sub> inhibitorp-bromophenacyl-bromide or calmodulin antagonist chlorpromazine and calcium ion chelate EG-TA obviously decreased H<sub>2</sub>O<sub>2</sub> induced increment of EC-PMN adhesion.These results suggestthat H<sub>2</sub>O<sub>2</sub> may activate ECs,causing the inflow of extracellular calcium or the release of calciumfrom intracellular deposits.Increased intracellar Ca<sup>2+</sup>may bind with calmodulin to activate phos-pholipase A<sub>2</sub>,thus initiating PAF synthesis and promoting EC-PMN adhesion.
文摘This review described origination, biosynthesis and functions of platelet-activating factor (PAF) in the reproductive system of mammals and human beings. The article mainly focused on biological roles of the phospholipid mediator in sperm fertilization and embryonic implantation. As an autocrine product of sperm and embryos, PAF markedly stimulates sperm motility and fertilization and serves as a capacitation factor in a ligand-receptor manner, After fertilization, embryo-derived PAF improves its own development, especially from fertilized ova to blastocyst stage and is thought to act as an embryo growth factor in the same manner as on sperm. Its mechanism of action was also clarified. At the end, it was presented some advances in its clinical application, followed by discussion of some issues possibly concerning in its current application.
文摘Objective: To study the serum platelet-activating factor (PAF) level of patients with cerebral infarction from transient ischemic attack (TIA) and its correlation with coagulation function and inflammatory response. Methods: TIA patients who were hospitalized in Neurology Department of Foshan Second People's Hospital between September 2016 and July 2017 were selected and divided into simple TIA group and cerebral infarction group according to the progression into cerebral infarction or not within 1 week;healthy subjects who received physical examination during the same period were selected as the control group. Serum levels of PAF, coagulation function indexes and inflammation indexes were detected. Results: Serum PAF, FVIII, vWF, TNF-α, hs-CRP, MCP-1 and IL-17 contents of cerebral infarction group and simple TIA group were significantly higher than those of control group while PT, APTT and TT levels were significantly shorter than those of control group;serum PAF, FVIII, vWF, TNF-α, hs-CRP, MCP-1 and IL-17 contents of cerebral infarction group were significantly higher than those of simple TIA group while PT, APTT and TT levels were significantly shorter than those of simple TIA group;serum FVIII, vWF, TNF-α, hs-CRP, MCP-1 and IL-17 contents of TIA patients with high PAF content were significantly higher than those of TIA patients with low PAF content while PT, APTT and TT levels were significantly shorter than those of TIA patients with low PAF content. Conclusion: Excessively generated PAF can promote TIA progression to cerebral infarction by activating coagulation pathway and inflammatory response.
文摘The activity of plasma platelet-activating factor(PAF) from pregnant women before and after delivery was determined. Plasma samples were taken from 74 pregnant women, among whom 24 were normotensive controls, 30 mild and moderate hypertensive and 20 severe hypertensive. Of the two hypertensive groups(pregnancy-induced hypertension, PIH), PAF activity measured by a bioassay was significantly higher than that of normotensive control at 38 weeks in gestation , indicating a possible role of this potent lipid mediator in the pathophysiological mechanism of PIH. After delivery, PAF activity was obviously increased in all three groups , showing the regulation of placenta in PAF metabolism.
基金Supported by the National Natural Science Foundation of China(No.81072726)
文摘Objective: To explore the association of the platelet-activating factor receptor(PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease(CHD) and blood stasis syndrome(BSS) of CHD in Chinese Han population. Methods: A total of 570 CHD patients(299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaP shot technology. The statistical analysis was conducted using a multiple variable logistic regression model. Results: Significant differences were detected in the genotypes frequency distributions of the rs5938(P<0.01), but not the rs313152(P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio(aOR)=0.35, 95% confidence interval(CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD(aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD(aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS(aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS(aOR=1.22, 95% CI: 0.81 to 1.85, P>0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27(95% CI: 0.1 to 0.7, P<0.01). Conclusion: The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.
基金This work was supported by National Institute on Alcohol Abuse and Alcoholism(NIAAA)017748.
文摘“Let’s Move!”is a comprehensive initiative,launched by the First Lady,Michelle Obama,dedicates to solving problems of obesity,which is growing in child.The life behaviors do affect obesity;however,the mechanistic insight in molecular level is still not clear.In this study,by continually monitoring mouse body weight under chow and high fat western diets as well as metabolic,physical activity and food intake behaviors assessed in a CLAMS Comprehensive Lab Animal Monitoring System,we demonstrated that the platelet-activating factor receptor(PTAFR)contributes to modification of life behaviors.PTAFR does not affect metabolism of ingested dietary fat and carbohydrate in young animals;however,Ptafr ablation dramatically increased weight gain without affecting adipose tissue accumulation.Ptafr/mice possess new habits that increased food intake and decreased movement.Our studies suggest that regulation of PTAFR activity may be a novel strategy to control obesity in children or young adults.