Isolation and Characterization of Platelet-Activating Factor (PAF) Inhibitors from Zanthoxylum schinifolium

Two new compounds,schinifolin Ⅰ and acetoxyschinifolin Ⅱ,along with five known compounds(auraptenⅢ,dictamnine Ⅳ,scoparone Ⅴ,skimmianine Ⅵ,and β-sitosterol Ⅶ)were isolated from the roots of Zanthoxylum schinifolium Sieb.et Zucc.col- lected in Yixing County,Jiangsu Province.The structure determination was based upon spectroscopic analysis(UV,IR,MS,PMR,CMR,2D NMR).The structures of schinifolin Ⅰ and acetoxyschinifolin Ⅱ were elucidated as 7[(3′,7′-dimethyl-2′,6′-octadienyl)] oxy-8-methoxy-2H-1-benzopyran-2-one,and 7[(3′,7′-dimethyl-5′-acetoxy-2′, 6′-octadienyl)]oxy-8-methoxy-2H-1-benzopyran-2-one,respectively. In the test of platelet aggregation caused by PAF,compounds Ⅰ,Ⅱ,Ⅲ and Ⅴ showed inhibitory activity.

Therapy for acute pancreatitis with platelet-activating factor receptor antagonists

Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAF- RAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.

Role of platelet-activating factor in pathogenesis of acute pancreatitis

Platelet-activating factor(PAF)is a potentproinflammatory phospholipid mediator that belongsto a family of biologically active,structurally relatedalkyl phosphoglycerides with diverse pathologicaland physiological effects.This bioactive phospholipidmediates processes as diverse as wound healing,physiological inflammation,angiogenesis,apoptosis,reproduction and long-term potentiation.PAF actsby binding to a specific G protein-coupled receptorto activate multiple intracellular signaling pathways.Since most cells both synthesize and release PAFand express PAF receptors,PAF has potent biologicalactions in a broad range of cell types and tissues.Inappropriate activation of this signaling pathway isassociated with many diseases in which inflammationis thought to be one of the underlying features.Acutepancreatitis(AP)is a common inflammatory disease.The onset of AP is pancreatic autodigestion mediatedby abnormal activation of pancreatic enzyme caused bymultiple agents,which subsequently induce pancreaticand systemic inflammatory reactions.A number ofexperimental pancreatitis and clinical trials indicatethat PAF does play a critical role in the pathogenesisof AP.Administration of PAF receptor antagonist cansignificantly reduce local and systemic events that occurin AP.This review focuses on the aspects that are morerelevant to the pathogenesis of AP.

Role of platelet-activating factor in reproduction:sperm function

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.

Roles of BN52021 in platelet-activating factor pathway in inflammatory MS1 cells

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.

Determination of platelet-activating factor by reverse phase high-performance liquid chromatography and its application in viral hepatitis

AIM： To detect the plateletoactivating factor （PAF） and the plasma or serum levels of tumor necrosis factoroa （TNF-α） malondialdehyde （MDA）, endotoxin （ET） and to discuss their significance in various types of viral hepatitis. METHODS： PAF, TNF-α, MDA, and ET levels in 60 controls, 16 cases of acute viral hepatitis, 71 cases of chronic viral hepatitis, 19 cases of severe viral hepatitis were detected by reverse phase high-performance liquid chromatography （rHPLC）, bio-assay, ELISA, thiobarbituric acid （TBA）, and limulus lysate test （LLT）, respectively. RESULTS： The rHPLC was more sensitive and specific than bio-assay （r = 0.912, P〈0.01）. The plasma levels of PAF, TNF-α, MDA, and ET in patients with viral hepatitis were higher than those in controls （P〈0.01）. CONCLUSION： rHPLC is more reliable and accurate for the detection of PAF.

Compound Kushen injection induces immediate hypersensitivity reaction through promoting the production of platelet-activating factor via de novo pathway

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.

The Activity of Plasma Platelet-activating Factor Derived from Pregnant Women before and after Delivery and lts Relation to Pregnancy-induced Hypertension

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.

The actions,detection and synthesis of platelet-activating factor (PAF) in mammalian pregnancy

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.

Platelet-activating factor mediates hydrogen peroxide induced endothelial-leukocyte adhesion

The effects of hydrogen peroxide（H2O2）on endothelial-polymorphonuclear leuko-cyte（EC-PMN）adhesion and their mechanisms were studied in cultured bovine pulmonaryartery endothelial monolayers in vitro.H2O2 at various concentrations(10-3,10-2,10-1mol/Lrespectively)stimulated EC-dependent PMN adhesion,of which 10-2mol/L H2O2 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 H2O2induced EC-PMN adhesion.Pretreatment of ECs with SRI 63-441 before H2O2 exposure signifi-cantly decreased PMN adherence to ECs.Pretreatment of ECs with phospholipase A2 inhibitorp-bromophenacyl-bromide or calmodulin antagonist chlorpromazine and calcium ion chelate EG-TA obviously decreased H2O2 induced increment of EC-PMN adhesion.These results suggestthat H2O2 may activate ECs,causing the inflow of extracellular calcium or the release of calciumfrom intracellular deposits.Increased intracellar Ca2+may bind with calmodulin to activate phos-pholipase A2,thus initiating PAF synthesis and promoting EC-PMN adhesion.

The inhibitory effects of β-adrenoceptor activation on vascular permeability increment induced by platelet-activating factor and histamine

The effects of isoproterenol (IPN) on histamine and platelet-activating factor (PAF)-induced vascular permeability increment in rat skin and in cultured confluent endothelial cell monolayer were investigated. The results showed that after intravenous administration of 20 mg/kg Evans blue (EB) dye, the intradermal injection of 0. 2 ml PAF(10-7mol/L) or histamine (0. 5 mmol/L) could induce the exudation of 16. 82+2. 05 μg/g tissue and 21. 86+2. 86μg/g tissue of EB respectively into the injected skin. Pretreatment of the rats with intravenous IPN (10 μg/kg) decreased the EB exudation by 56. 2% and 43. 6% respectively. Propranolol (PPN), a β-adrenoceptor blocker, reversed the inhibitory effects of IPN. In rats treated with PPN alone, intradermal injection of PAF and histamine induced significant increase of skin EB exudation in comparison with the control, indicating that catecholamines at physiologic concentration in vivo may have inhibitory effects on vascular permeability. When cultured endothelial cell monolayers were perfused with 1% albumin in Hanks' balanced salt solution the increased fluid flux and protein clearance caused by PAF were significantly decreased by IPN pretreatment. The results confirmed the inhibitory effects of IPN on vascular permeability increment induced by PAF at the cellular level.

Physiological Roles of Platelet-activating Factor in Mammalian and Human Reproduction

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.

Serum platelet-activating factor level of patients with cerebral infarction from TIA and its correlation with coagulation function and inflammatory response

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.

Regulatory effects of phospholipase A_2 inhibitors on platelet activating factor in endotoxic shock in rabbits

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.

PAFAH1B3表达水平与多发性骨髓瘤患者自体造血干细胞移植后疾病进展风险的相关性

目的:探讨接受自体造血干细胞移植(AHSCT)治疗的多发性骨髓瘤(MM)患者骨髓CD138^(+)细胞中血小板激活因子乙酰水解酶1B3(platelet-activating factor acetylhydrolase 1B3,PAFAH1B3)基因表达水平与2年内预后之间的相关性。方法:选取2014年5月至2019年5月间于南通大学第一、第二附属医院就诊的147例行AHSCT治疗的MM患者作为研究对象,检测患者骨髓CD138^(+)细胞中PAFAH1B3 mRNA的表达水平,并将随访2年间疾病进展或死亡者纳入进展组,其余纳入预后良好组。比较两组患者的临床资料和PAFAH1B3 mRNA表达水平,以入组患者PAFAH1B3 mRNA表达水平中位数为界将患者分为PAFAH1B3高表达组和低表达组,采用Kaplan-Meier法比较两组患者的无进展生存率(PFSR)。应用单因素分析和多因素COX回归分析法分析患者2年内预后的相关因素。结果:随访结束时共有13/147例患者失访,最终进展组纳入44例,预后良好组纳入90例。进展组年龄高于预后良好组,移植后达CR^(+)VGPR患者比例低于预后良好组,两组ISS分期例数分布差异有统计学意义(均P<0.05);进展组PAFAH1B3 mRNA表达水平和LDH>250 U/L患者比例均高于预后良好组,PLT值低于预后良好组(均P<0.05);PAFAH1B3高表达组2年PFSR显著低于低表达组(log rankχ^(2)=8.167,P=0.004);LDH>250 U/L(HR=3.389,P=0.010)、PAFAH1B3 mRNA表达水平(HR=50.561,P=0.001)和ISSⅢ期(HR=1.000,P=0.003)为患者预后的独立危险因素,ISSⅠ期(HR=0.133,P=0.001)为患者预后的独立保护因素。结论:接受AHSCT治疗的MM患者骨髓CD138^(+)细胞中PAFAH1B3 mRNA表达水平与预后相关,检测PAFAH1B3 mRNA表达水平对预测患者的PFSR和预后分层具有一定意义。

Association of Platelet-Activating Factor Receptor Gene rs5938(G/T) and rs313152(T/C) Polymorphisms with Coronary Heart Disease and Blood Stasis Syndrome in A Chinese Han Population

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.

Platelet-activating factor receptor affects food intake and body weight

“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.

PCOS患者PAF-AH活性及其与糖脂代谢相关性的研究

目的探讨多囊卵巢综合征(PCOS)患者血小板活化因子乙酰水解酶(PAF-AH)活性及其与糖脂代谢的关系。方法按照鹿特丹标准筛选PCOS患者87例,同时选取年龄匹配的健康妇女83名作为对照。①用化学发光法检测血清雌二醇(E2)、总睾酮(TT)、黄体生成素(LH)、促卵泡激素(FSH)、空腹胰岛素(FINS);②用酶法试剂盒测定空腹血糖(FGLU)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C);③用[3H-acelty]PAF示踪三氯醋酸沉淀法检测血浆PAF-AH活性。结果①PCOS组体重指数(BMI)、腰臀比(WHR)、F-G评分、血清TT水平、LH/FSH比值高于对照组(P<0.01)。②PCOS组血清FINS、胰岛素抵抗指数(HOMA-IR)、TG、TC、LDL-C、非高密度脂蛋白胆固醇(non-HDL-C)和致动脉粥样硬化指数(AI)高于对照组(P<0.01),而HDL-C水平低于对照组(P<0.01)。但血浆PAF-AH活性两组间差异无统计学意义(P>0.05)。③非肥胖PCOS患者(BMI<25 kg/m2)FINS、HOMA-IR、LDL-C、non-HDL-C、AI高于非肥胖对照妇女(P<0.05)。肥胖PCOS患者(BMI≥25 kg/m2)除了更严重的上述代谢异常外,FGLU、TG、TC、BMI、WHR、收缩压(SBP)、舒张压(DBP)也明显升高(P<0.05),HDL-C水平明显降低(P<0.05)。然而非肥胖对照、非肥胖PCOS与肥胖PCOS三亚组间血浆PAF-AH活性差异无统计学意义(P>0.05)。④Person相关分析表明:PCOS组血浆PAF-AH活性分别与non-HDL-C、LDL-C、AI、TG、TG、WHR呈正相关,与HDL-C呈负相关(P<0.05)。多重线性回归表明:non-HDL-C与SBP是PCOS组血浆PAF-AH活性有意义的预测因子(P<0.05)。结论PCOS组血浆PAF-AH活性与对照组比较无明显改变,血脂特别是胆固醇与血浆PAF-AH活性相关联。肥胖PCOS患者比非肥胖PCOS患者表现出更严重的脂代谢异常与胰岛素抵抗。

血小板活化因子及其乙酰水解酶在新生儿感染中的变化及临床意义

目的检测感染新生儿血浆血小板活化因子(PAF)水平及其乙酰水解酶(PAF-AH)的活性,探讨两者在新生儿感染中的变化及临床意义。方法以复旦大学附属儿科医院新生儿科病房收治的日龄<30d的新生儿为研究对象。依据感染部位和程度分为全身感染组、局部感染组及非感染组;依据日龄分为早期新生儿(≤7d)和晚期新生儿(>7d)。采集研究对象桡动脉血标本,对全身感染组中合并器官功能衰竭的患儿在感染的第1、3、5和7天增加采集桡动脉血标本。测定血浆PAF水平(μg.L-1)和PAF-AH活性(μmol.L-1.min-1)。分析感染程度、性别、日龄和出生体重对血浆PAF水平和PAF-AH活性的影响,比较不同感染组PAF水平和PAF-AH活性的差异,观察全身感染合并器官功能衰竭患儿血浆PAF水平和PAF-AH活性在病程1～7d的变化趋势。结果研究期间共收治247例新生儿,男146例,女101例;平均日龄9.2(1～57)d;平均胎龄35.85(27～43)周;平均出生体重2517(906～4750)g。全身感染组91例,局部感染组63例,非感染组93例。①新生儿血浆PAF水平与感染程度相关(P=0.000);血浆PAF-AH活性与感染程度及日龄(P均为0.000)相关。②全身感染组血浆PAF水平(9.5±8.1)显著高于局部感染组(5.3±3.2)及非感染组(4.6±3.5)。早期新生儿中,全身感染组血浆PAF-AH活性(5.7±2.7)显著低于局部感染组(7.3±2.9)和非感染组(7.3±2.5)。晚期新生儿中,全身感染组血浆PAF-AH活性(7.0±2.5)显著低于局部感染组(9.7±2.2)和非感染组(9.7±2.7)。③全身感染组合并器官功能衰竭的9/12例存活患儿在病程的1～7d血浆PAF水平呈下降趋势,PAF-AH活性呈上升趋势。3/12例死亡患儿中两者的变化趋势则相反。④全身感染组31/91例确诊败血症患儿中,革兰阴性菌感染者血浆PAF水平(13.1±11.0)显著高于革兰阳性菌感染者(5.4±3.9),PAF-AH活性(4.9±2.1)显著低于革兰阳性菌感染者(7.9±2.4)。结论新生儿严重感染时血浆PAF水平增高,PAF-AH活性降低,两者的变化趋势与预后相关。

哮喘患儿血小板活化因子乙酰水解酶活性的研究

目的 探讨哮喘患儿血小板活化因子乙酰水解酶 (PAF AH)活性与病情的关系 ,及其活性与基因型的关系。方法 应用酶水解底物显色法测定不同病情哮喘患儿和健康儿童PAF AH活性。应用等位基因特异性聚合酶链式反应 (AS PCR)技术检测PAF AH基因第 9外显子Val2 79Phe基因型。结果 重度哮喘组血浆PAF AH活性明显低于轻、中度哮喘组和对照组 ,酶活性缺失率重度组占 15.4% ,而轻、中度哮喘组和对照组酶活性缺失率占 2 %～ 3 %。哮喘组及对照组 3种基因型 (Val/Val、Val/Phe和Phe/Phe)血浆PAH AH活性间比较有显著性差异 (P均 <0 .0 1) ,同一种基因型PAH AH活性哮喘组与对照组相比无显著性差异 (P >0 .0 5)。结论 血浆PAF AH活性与哮喘严重程度相关联 ,重度哮喘组酶活性显著低于轻、中度哮喘组和对照组 ;血浆PAF AH活性与PAF AH(Val2 79Phe)