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Objective To investigate the roles of a epoprostenol(PGI2) analog (Iloprost) in regulating the differentiation of CD4+ T cells to Treg cells and the possible mechanism.Methods Naǐve CD4+ T cells were isolated from human peripheral blood samples by using the magnetic-activated cell sorting (MACS) and then cultured under Treg-polarizing condition.The percentages of Treg cells and the expression of Foxp3 at mRNA level were respectively measured by using flow cytometry and RT-PCR for evaluation the effects of Iloprost on the differentiation of CD4+ T cells to Treg cells.The cAMP accumulation assay was used to detect the level of intracellular cAMP.Flow cytometry analysis was performed to detect the phosphorylation of signal transducer and activator of transcription 5 (STAT5).Results lloprost decreased the percentage of Treg cells and inhibited the expression of Foxp3 at mRNA level in a dose dependent manner (P＜0.05).However,the inhibitory effects of Iloprost were weakened when IP receptors were blocked by IP antagonist (CAY10449).A six-fold increase in the levels of intracellular cAMP in Treg cells was induced by Iloprost (P＜0.05) and a similar effect could be achieved by using a cAMP agonist,db-cAMP (P＞0.05).H-89,a protein kinase A inhibitor,inhibited the Iloprost-induced expression of cAMP in Treg cells.Moreover,Iloprost inhibited the IL-2 mediated phosphorylation of STAT5 (P＜0.05) and a similar effect could be achieved by using db-cAMP (P＞0.05).The Iloprost-mediated down-regulation of pSTAT5 was blocked by using H-89.Conclusion PGI2 could activate the cAMP-PKA signaling pathway by binding to the IP receptor,resulting in inhibited phosphorylation of STAT5 and suppressed differentiation of naǐve CD4+ T cells to Treg cells.
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OBJECTIVE: To investigate the effect of potassiam 2-(1-hydroxypentyl)-benzoae (dl/-PHPB) on platelet aggregation, the balance of PGI2/TXA, and fibrinolytic system of rats. METHODS: Rats were randomly divided into 5 groups; control group, low (1.3 mg·kg-1), middle (3.9 mg·kg-1) and high (12.9 mg·kg-1) dose of dl-PHPB groups and ticlopidine group. Blood was taken from the abdominal aorta 30 min after dl-PHPB administrated intravenously, and the rate of platelet aggregation was detected by platelet aggregometer. The expression of CD62p on the surface of platelet was determined by flow cytometry. The contents of 6-Keto-PGF1α, thromboxane B2 (TXB2), t-PA and PAT-1 in serum were measured by radio-immuno assay and FLISA kit, respectively. RESULTS: dl-PHPB inhibited rat platelet aggregation induced by A DP in dose-dependent manner more potently compared with AA, collagen and thrombin. dl-PHPB also decreased the expression of CD62p. It increased the level of 6-keto-PGF1α, the metabolite of prostaglandin I2 (PGL2) and reduced the content of PAI-1. But dl/-PHPB had no effect on the contents of TXB2 the metabolite of TXA2 and t-PA. CONCLUSION: dl-PHPB may significantly inhibit rat platelet aggregation induced by ADP, increase the ratio of PG12/TXA2 and enhance the activity of fibrinolytic system.
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Objective To discuss the changes of plasma TXA2 and PGI2 levels in the rabbit model of pulmonary hypertension (PHA)induced by monocrotaline (MCT)when transplanted with endothelial progenitor cells (EPCs). Methods The rabbit pulmonary hypertension model was constructed by MCT induction. Rabbit endothelial progenitor cells were induced,separated and identified in vitro.50 New Zealand white rabbits were randomly divided into 3 groups,normal control group and model group were given M199 culture medium by tail vein injection,EPCs treatment group were given EPCs marked with fluorescent though tail vein injection. The levels of plasma TXB2 and 6-keto-PGF1αwere detected and their ratio were calculated after three weeks. Results Compared with model group,the content of 6-keto-PGFlαin plasma in EPCs group was (130.67 ±17.54)u mol/L,which was increased sinnificantly. The content of TXB2 was (402.89 ±27.98 )u mol/L,which was decreased significantly.The ratio of TXB2 to 6-keto-PGF1 alpha between two groups was statistically significant(P<0.01 ). Conclusion EPCs transplantation can reduce the content of TXA2 and increase the content of PGI2 in the pulmonary hypertension rabbits induced by monocrotaline,then reverse the damage of pulmonary hypertension.
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Objective To compare the effects of compound salvia miltiorrhiza pill and salvia milti-orrhiza pill on platelet activation in hematoplasma in patients with coronary atherosclerosis , and guide clini-cal medication .Methods Ninety cases suffered coronary atherosclerosis who were treated with compound salvia miltiorrhiza, salvia miltiorrhiza and palcebo for two months course of treatment were divided into com-pound salvia miltiorrhiza , salvia miltiorrhiza and control groups , Normal group included 30 physical fitness were treated with placebo.Contents of PTGIS mRNA, cAMP, TXA2 and PGI2 in hematoplasma were treated with palcebo.Contents of PTGIS mRNA, cAMP, TXA2 and PGI2 in hematoplasma were detected by real-time RT-PCR and radioimmunoassay , respectively.Res ults In coronary atherosclerosis groups , cAMP, TXA2 ., PTGIS mRNA were decreased markedly , TXA2 were increased markedly. Compund salvia miltior-rhiza and salvia miltiorrhiza could increase the expression of cAMP , PGI2 and PTGIS mRNA but TXA2 , the content of TXA2 .in compund salvia miltiorrhza and salvia miltiorrhiza groups were decreased .Conclusion Compound salvia miltiorrhiza and salvia miltiorrhiza can inhibit plateled activation .The effect on inhibi-ting platelet activation of compound salvia miltiorrhiza is better than salvia miltiorrhiza .
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In order to explore the changes and the roles of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage, 31 cases subject to crani- otomy were divided into three groups: group A, 9 patients with postoperative hypertensive crisis; group B, 13 patients without postoperative hypertensive crisis; and group C, 9 patients without his- tory of hypertension and hypertensive intracerebral hemorrhage. TXA2＞, TXB2＞, 6-keto-PGF1α and PGI2＞ were measured after operation in the three groups respectively. The postoperative blood pres- sure in group A, including SBP and DBP, was elevated more obviously than that in the other two groups. TXA2＞ and PGI2＞ in group A were significantly higher than those in other two groups (P＜0.01). Moreover, the ratio of TXB2＞ to 6-keto-PGF1α in group A was significantly higher than that in other two groups (P＜0.05). The increase of TXA2＞ and the relative inadequacy of prostacyclin, especially 6-keto-PGF1α, may play roles in the postoperative hypertensive crisis. And the increased value of TXB2＞ to 6-keto-PGF1α could provide the basis for diagnosis of postoperative hypertensive crisis.
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@#ObjectiveTo investigate the effect of Jiuqiang Naoliqing(JNQ) on the TXA2 and PGI2 level in spontaneous hypertension rat (SHR) plasma.MethodsThe plasma was separated after the SHR and Wistar rats were treated with JNQ at the dose of 0.133g/kg,0.265g/kg,0.530g/kg and 1% carboxymethyl cellulose respectively for 5 weeks. The level of TXB2 and 6 keto PGF1α ,stable metabolin of TXA2 and PGI 2,in SHR plasma was tested by radioimmunoassay.ResultsThe level of TXB2 and the ratio of TXB2/6 keto PGF1α (T/P) in SHR plasma increased significantly(P<0.01),and there was no significant difference in the concentration of 6 keto PGF1α between Wistar rats and SHR plasma(P>0.05). JNQ could increase the generation of 6 keto PGF1α and decrease the level of TXB2 and T/P in SHR plasma after treated with different dosages for 5 weeks.ConclusionJNQ may improve the balance between TXA2 and PGI2 in SHR plasma.
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Objective To investigate the pathogenesis of avascular necrosis of femoral head (ANFH) and to compare the effectiveness of ultrashort wave diathermy and Chinese medicine in the treatment of avascular necrosis of femoral head (ANFH) through animal experiment. Methods A total of 40 New Zealand white rabbits were divided into four groups: a control group, a model group, an ultrashort wave group, a Chinese me-dicine group. All the groups were injected with horse blood serum and methyl-prednisolone, which can induce ANFH. The TXB_2, 6-keto-PGF_ 1? , TG, TCh and hemorheology index were observed in the study. Results When compared with control group, the difference of model group was significant (P0.05) between ultrashort wave group and Chinese group. Conclusion Both ultrashort wave diathermy and Chinese medicine were effective for the treatment of ANTH in the early stage.
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Objective To investigate the effects of puerarin on levels of thromboxane A 2 (TXA 2) and prostaglandin I 2 (PGI 2) in plasma of rats with hyperlipidemia. Methods A total of 48 Wistar juvenile rats were randomly divided into four groups: normal diet, high fat and high cholesterol diet (HFD), HFD supplemented respectively with 1 g/kg puerarin (puerarin group Ⅰ) or 2 g/kg puerarin (puerarin group Ⅱ). After eight weeks of feeding, the rats were sacrificed for detection of the levels of lipid, TXA 2, and PGI 2. Results The blood triglycerol, total cholesterol, LDL C, TXA 2, and TXA 2/PGI 2 were significantly lower in puetarin Ⅰ and puerarin Ⅱ groups than those in HFD group, but the concentration of HDL C was significantly increased in the supplemented group( F =109 163, P =0 000; P
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BACKGRUOND: Several angiogenic factors such as bFGF and VEGF have been shown angiogenesis of placenta. PGE2 and PGI2 may be important in successful establishment of pregnancy. OBJECTIVE: We studied to investigate whether PGE2 and PGI2 regulate expression of VEGF and bFGF gene in the cultured human trophoblast cells. METHODS: Human trophoblasts were isolated from the placenta of early gestation (6-12 weeks). Isolated trophoblasts were cultured in the different concentration of PGE2 and PGI2 and according to the different cultured time of PGE2 and PGI2, respectively. Total RNA was extracted and RT-PCR was performed. RESULT: Expression of bFGF was increased in 10-7M and 10-6M of PGE2 and was always increased in the all different concentration of PGI2. Four isoforms (VEGF121, VEGF165, VEGF189, VEGF206) were always expressed in the all different PGE2 and PGI2 concentration compared to the control group. However, there was no significant difference in the all different PGE2 and PGI2 concentration. In both PGE2 and PGI2 treatment group, expression of bFGF was decreased at 60 min compared to the control group and was gradually increased in time-dependent pattern. At 180 min, its expression was similar to the control group. CONCLUSION: Our data suggest that the expression of bFGF gene is influenced by cultured time and concentration of PGE2 and PGI2, although the expression of VEGF gene is not influenced.
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Humans , Pregnancy , Angiogenesis Inducing Agents , Dinoprostone , Epoprostenol , Fibroblast Growth Factor 2 , Placenta , Protein Isoforms , RNA , Trophoblasts , Vascular Endothelial Growth Factor AABSTRACT
AIM:To study the effects and mechanisms of a novel sulfonylureous compound 1 ｛4 [2 (4 bromobenzenesulfonaminoethyl)phenylsufonyl｝ 3 (trans 4 methylcyclohexyl) urea, G004, on antithrombosis. METHODS: The influence of compound G004 on the vasoconstrictor action, platelet aggregation and thrombosis formation was studied. The effects of compound G004 on the tail vein bleeding time in mice was examined. The influence of compound G004 on the release of prostanglandin I 2 and thromboxan A 2 from ECV304 cells was investigated. The measurement of cytosolic free Ca 2+ in attached ECV304 cells loaded with Fluo3/AM was carried out. RESULTS: Compound G004 did not inhibit the contraction of rat aorta rings induced by norepinephrine or potassium chloride, but potently inhibit human platelet aggregation challenged by arachidonic acid and adenosine diphosphate. Compound G004 significantly prolonged the tail vein bleeding time in mice and occlusion time of carotid artery in experimentally thrombotic rats. Compound G004 reduced mice mortality induced by the collagen plus epinephrine in a dose dependent manner. Compound G004 enhanced PGI 2 release and reduced TXA 2 secretion from ECV304 cells. G004 had no effect on the increase of cytosolic free Ca 2+ induced by patassium chloride. CONCLUSION: The compound G004 has a remarkable antithrombotic effect in vivo. Its active mechanism may be attributed to inhibition of platelet aggregation, enhancing PGI 2 generation and decreasing TXA 2 secretion from human umbilical vein endothelium.
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Objective To explore the PGI 2 and TXA 2 for lung cancer patients and ones with lung cancer metastasis,in onder to provide nomal index for diagnosis and differential diagnosis in lung cancer metastasis.Methods To test plasma PGI 2 and TXA 2 by means of RIA in all cases.One group of patients who received non operative treatment:Six cases of patients with distant metastasis;Eight cases with hilus of long metastasis;Seven cases without metastasis.The other group of patients who received radical operation;Six cases of patients with distant metastasis;Seven cases with hilus of lung metastasis;Six cases without metastasis.Result The PGI 2/TXA 2 ratio of the patient whether distant metastasis or hilus of lung metastasis was obviously lower than that of the patients without metastasis( P
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Aim To further research into the antithrombotic mechanism of scorpion venom active peptides (SVAP). Methods Human umbilical vein endothelial cells (HUVEC) were cultured with enzyme digestive method. After the cultured HUVC was incubated in conditioned media for 1 hour, the effects of SVAP on the concentration of 6-Keto-PGF 1? and NO of HUVEC were determined with radioactive-immunolygic and nitrate reduction enzyme method respectively. Results As compared with control, SVAP in the doses of 1,5,10, 20 mg?L -1 had the distinctive increase of 54%, 68%,72%,79% of the concentration of 6-Keto-PGF 1? and SVAP in the doses of 10, 20 mg?L -1 had the significantly increased of 27%, 46% of the concentration of NO. Regression anylysis showed that the release levels of PGI 2 and NO in HUVEC induced by SVAP was of positive correlation. Conclusion Antithrombotic mechanism of SVAP is related to the increase of PGI 2 and NO released from HUVEC and synergistic and mediating action between NO and PGI 2.
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BACKGROUND: Prostacyclin administered intravenously has demonstrated intermediate pulmonary specificity and its aerosol form has an even greater pulmonary selectivity. There have been few systematic analyses of the difference in response according to the route of administration and the dose of administration of prostacyclin. So we have compared prostacyclin infusion versus inhalation in various concentrations in an animal model. METHODS: Pulmonary hypertension was induced by continuous intravenous infusion of the vasoconstrictor U46619 and prostacyclin solutions of 10, 50, 100, 200 mcg/ml were inhaled using a jet nebulizer. Prostacyclin infusion was done at a rate of 100, 200, 400 ng/kg/min. RESULTS: With inhalation of 10, 50, 100, 200 mcg/ml prostacyclin, PVR fell to values of 85%, 76%, 64%, 55% of the preinhalation value and SVR fell to values of 94%, 80%, 76%, 64% of the preinhalation value, respectively (p<0.05). PVR/SVR ratios decreased significantly in all inhalation doses (p<0.05). With infusion of prostacyclin at a rate of 100, 200, 400 ng/kg/min, PVR fell to values of 73%, 60%, 50% of the preinfusion value and SVR fell to values of 68%, 54%, 38% of the preinfusion value, respectively (p<0.05). PVR/SVR ratios increased at an infusion rate of 400 ng/kg/min. CONCLUSION: Prostacyclin inhalation did not result in selective pulmonary vasodilation without causing any efects on the systemic vascular bed (absolute pulmonary selectivity). But it did cause more predominant vasodilation on the pulmonary vascular bed (relative pulmonary selectivity). By contrast, prostacyclin infusion caused more predominant vasodilation on the systemic vascular bed, creating the risk of severe systemic hypotension.
Subject(s)
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid , Epoprostenol , Hypertension, Pulmonary , Hypotension , Infusions, Intravenous , Inhalation , Models, Animal , Nebulizers and Vaporizers , Sensitivity and Specificity , VasodilationABSTRACT
Object To observe the effect of 20S-protopanaxadiol saponins from Panax quinquefolium (PPDS) on total cholesterol, lipoprotein cholesterol metabolism and antioxidative activity in experimental hyperlipidemia rats. Methods The total cholesterol (TC), lipoprotein cholesterol, and lipid peroxidation (LPO) contents, prostaglandin I 2 (PGI 2), thromboxane A 2 (TXA 2) levels, superoxide dismutase (SOD) activity and blood viscosity were measured in hyperlipidemia rats which have been given PPDS 25, 50, 100 mg/(kg?d) by ip, continuously for 12 days. In addition, fat accumulation in liver was observed. Results Triglyceride (TG), TC, low density lipoprotein cholesterol (LDL-c) in serum, TXA 2 in plasma, LPO in serum and liver, and blood viscosity were decreased significantly; and high density lipoprotein cholesterol (HDL-c) in serum, PGI 2 in plasma, and SOD in serum and liver were significantly increased by given PPDS [50, 100 mg/(kg?d)] in experimental hyperlipidemia rats. Moreover, PPDS can decrease TC/HDL-c and LDL-c/HDL-c ratio, increase PGI 2/TXA 2 ratio, and inhibit fat accumulation in liver. Conclusion PPDS could inhibit arteriosclerosis by improving cholesterol and lipoprotein-cholesterol metabolism, suppressing LPO, and increasing the activity of SOD.
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AIM: To investigate the inhibiting effect and mechanism of dimethylaminoethyl ginkgolide B mesylate on platelet aggregation and release function.METHODS: The effect of dimethylaminoethyl ginkgolide B mesylate on inhibiting PAF-induced platelet aggregation was measured by turbidimetry method through giving rabbits dimethylaminoethyl ginkgolide B mesylate at different final concentration via i.v.for 5 days.The release of Ca2 + from PAF-induced platelet in rabbits was assayed with fluorospectrophotometry and the contents of TXA2 and PGI2 were measured by radio-immunity method.RESULTS: Three groups of dimethylaminoethyl ginkgolide B mesylate (1.95,3.90,7.80 mg/kg) had significant effect on inhibiting PAF-induced platelet aggregation in rabbits (compared to normal,P
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Objective: To research antithrombotic effect and mechanism of total saponins of Astragalus (TSA).Methods: Effects of TSA on artery thrombosis anud platelet aggregation were studied, at dosage of 50,100,200mg/kg. And level of TXA 2,PGI 2 in plasma, content of NO in serum of rats were determined.Results: TSA could restrain artery thrombosis and platelet aggregation of rats, and increase PGI 2 and NO.Conclusion: There was apparently antithrombotic effect of TSA.
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Objective: To study the influences of Tiaozhixin(TZX) on NO/ET, 6 keto PGF 1a /TXB 2 and hemorrheology rats with hyperlipoidemia. Methods: The rat hyperlipoidemia and early atheroscleorsis models were established by feeding high lipid diet for 40 days. Meanwhile TZX was taken by oral administration at the dosages of 40、80g/kg. The levels of NO、ET 1、6 keto PGF 1a and TXB 2 in serum were determind, and the hemorrheology markers were observed. Results: TZX could raise the levels of NO in serumobviourly ET 1 level of the normal and model rats. The large dose of TZX could increase 6 keto PGF 1a content remarkably which benefits maintenance of the balances of 6 keto PGF 1a /TXB 2. It could lower the whole blood specific viscosity, whole blood reduction specific viscosity, plasma specific viscosity; aggregation index of RBC; shorten RBC electrophoresis time; also decrease fibrinogen content; inhibit the platelet aggregation of normal rats induced by ADP. Conclusion: TZX can improve the abnormal hemorrheology and recover the balance of TXB 2/6 keto PGF 1a and NO/ET of rats with hyperlipoidemia, which might be one of mechanisms of antiatherosclerosis action.
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In order to explore the mechanism of cardiac damage by PTH, the release of PGI2 from heart cells was measured. The results showed that bPTH ( 1-34) increased the release of 6-keto-PGFla from heart cells in a dose dependent manner. Calcium inophone A23187 also increased the 6-keto-PGF1? release, while EDTA and verapamil reduced it. These suggest that the PGI2 synthesis in heart cells was affected by intra and extracellular calcium. The significance of bPTH( 1-34) induced increase of PGI2 synthesis might be associated with interference of energy metabolism, and then, cell damage.
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The influences of varied concentrations of AG on the 8H-TdR(3H-Thymidine ) incorporation inhibition rate and the release of PGI2 and TXA2 were studied in cultured human and rat lymphocytes . The results indicated that the AG increased the 3H-TdR incorporation inhibition rate on the concentrations of 1.5? 10-7mol/L and 3?10-7mol/L. Using the RIA method, authors find that AG on the concentrations of 4 ? 10-7mol/L, 4 ? 10-3mol/L and 4 ? 10-11mo/L can significantly decrease the cultured lymphocytes TXA2 release while has no clear influences on PGI2 release
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Objective To study the relationship between TXA 2/PGI2 and pulmonary hypertension in Congenital Heart Disease(CHD).Methods The serum concentration of TXB2/6-K-PGF1? was determined in 63 patients with CHD by radioimmunoassay. Results TXB2 ，TXB2 /6-K-PGF1? increased significantly in P H,while 6-K-PGF1? decreased,the TXB2 /6-K-PGF1? varied in different PH groups(P＜0.05).Conclusion TXA2/PGI2 plays an important role in the pathogenesis of PH se- condary to CHD.