OBJECTIVETo investigate the dynamic changes of plasma levels of prostacycline (PGI2) and thromboxane A2 (TXA2) and their relationship with the severity of hepatic injury in rats with nonalcoholic fatty liver disease (NAFLD).

METHODSWe established a NAFLD model, with a fat-rich diet consisting of 10% lard oil + 2% cholesterol, which was given to Sprague-Dawley rats (n=48) for a period of 8, 12, 16 and 24 weeks. The other rats were fed standard diets and were used as normal controls (n=24). At sacrifice, liver pathology scores were evaluated and plasma levels of PGI2, its stable metabolic product 6-keto-PGF1 alpha and TXA2, and TXB2 were determined by radioimmunoassay.

RESULTSSimple fatty livers were observed in the model group at 8 weeks. From 12 weeks to 24 weeks, the livers gradually progressed from simple steatohepatitis to liver fibrosis. Plasma levels of TXB2 in the model group increased higher than in the control group after 8 weeks [(52.4+/-3.15) ng/L vs (41.1+/-1.45) ng/L] and continued to increase over time, with the highest levels at 24 weeks [(117.7+/-7.47) ng/L]. A strong positive correlation (r=0.537) was seen between plasma TXB2 levels and the severity of liver injury. Plasma 6-keto-PGF1 alpha concentrations decreased in the model group in comparison with the control group after 8 weeks [(31.1+/-1.62) ng/L vs (36.5+/-1.68) ng/L] and continued to decrease over time, with the lowest concentrations at 24 weeks [(3.4+/-2.43) ng/L t=3.77]. A negative correlation was shown between the 6-keto-PGF1 alpha level and the severity of the liver injury.

CONCLUSIONA rat model of NAFLD was established successfully by feeding a fat-rich diet for 24 weeks. In this model, the imbalance of plasma PGI2 and TXA2 levels (increased TXB2 and decreased 6-keto-PGF1 alpha levels) may play a role in the pathogenesis of experimental NAFLD.

6-Ketoprostaglandin F1 alpha ; blood ; Animals ; Epoprostenol ; blood ; Fatty Liver ; blood ; Liver ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; blood ; Thromboxane B2 ; blood

OBJECTIVETo observe changes of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha(6-Keto-PGF1 alpha) and TXB2/6-Keto-PGF1 alpha (T/P) in lungs of rats drowned in hypothermic sea water and to assess their influence on the blood-gas.

METHODSRats of different groups were drowned nearly to death in hypothermic sea water and then taken out of the water rapidly, observed at room temperature, after that the following steps were taken in 5, 15, 30, 60, 240 min and 360 min groups, that were 1 ml arterial blood taken from left heart for blood-gas analysis including pH, PaO2 and PaCO2, rectal temperature observed; at last, the ratio of left dry lungs with left wet lungs was assessed, TXB2 and 6-Keto-PGF1 alpha in right lungs were examined in all above groups and dead group(14 rats dead, only 4 examined).

RESULTSThe rectal temperature[(20.13 +/- 0.48) degree C], pH(6.68 +/- 0.03), PaO2[(45.00 +/- 6.30) mm Hg)], TXB2[(97.46 +/- 17.46) ng/L] and 6-Keto-PGF1 alpha[(25.59 +/- 8.12) ng/L] dropped to the lowest point in the 5 minutes group(P < 0.01), while PaCO2[(89.18 +/- 5.10) mm Hg] reached the highest point(P < 0.01), all above items from 5 minutes group then showed a recovering tendency, but only the pH in 240 minutes and 360 minutes groups as well as TXB2 in 360 minutes group and dead group reached near the level of normal control groups (P > 0.05); T/P had a rising tendency and reached the highest point in the 360 minutes group.

CONCLUSIONSThe production and secretion of TXB2 and 6-Keto-PGF1 alpha were influenced by hypothermia, hypoxemia and acidosis, the imbalance of T/P could be one of factors influencing the improvement of blood gas index.

6-Ketoprostaglandin F1 alpha ; analysis ; Animals ; Body Temperature ; Carbon Dioxide ; blood ; Drowning ; metabolism ; Hypothermia ; metabolism ; Lung ; chemistry ; Oxygen ; blood ; Rats ; Seawater ; Thromboxane B2 ; analysis

OBJECTIVETo investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane B2 (TXB2) and 6-keto prostaglandin F 1alpha (PGF 1alpha) in 27 healthy free-living male subjects aged 30 to 55 years.

METHODSIt was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a 'wash-out period', before being assigned to the other diet for an additional 4 weeks.

RESULTSSerum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF 1alpha (P < 0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2.

CONCLUSIONSDiet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

6-Ketoprostaglandin F1 alpha ; urine ; Adult ; Arteriosclerosis ; physiopathology ; Cross-Over Studies ; Dietary Fats ; pharmacology ; Fatty Acids ; metabolism ; Humans ; Male ; Middle Aged ; Thrombosis ; physiopathology ; Thromboxane B2 ; analogs & derivatives ; urine

OBJECTIVETo explore the changes of the neurotransmitters in patients with chronic pulmonary heart disease (CPHD) and its clinical significance.

METHODSSeventy-two patients with CPHD (42 males, 30 females, mean age 55.6-/+8.9 years) were enrolled in the study, including 48 patients with compensated CPHD and 24 with uncompensated CPHD. Plasma endothelin (ET), thromboxance B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-K-PGFlalpha) were detected by radioimmunoassay. Thirty blood donors were selected as the normal control.

RESULTSCompared with the normal controls, CPHD patients showed abnormal pulmonary function, and significantly elevated levels of plasma ET and TXB2 (P<0.01) and lowered 6-K-PGFlalpha(P<0.01), but no significant differences were found between the patients with compensated CPHD and uncompensated CPHD (P>0.05). Plasma ET and TXB2 levels were inversely correlated to 6-K-PGFlalpha level (r=-0.4571, P<0.05).

CONCLUSIONThe patients with CPHD present with obvious changes of plasma ET, TXB2 and 6-K-PGFlalpha.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Case-Control Studies ; Chronic Disease ; Endothelins ; blood ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Heart Disease ; blood ; Thromboxane B2 ; blood

To explore the anti-platelet aggregation and anti-thrombotic mechanisms of Trichosanthis Fructus combined with aspirin based on network pharmacology and the validation of arteriovenous by pass model in rats. The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome(DRAR-CPI),Universal Protein Resource(Uniprot) and the Database for Annotation,Visualization,and Integrated Discovery(DAVID) were used to predict protein targets and analyze biological pathway and signal pathway in the combination of Trichosanthis Fructus with aspirin. The effects of pretreatment with Trichosanthis Fructus pellets,aspirin pellets and their combination on thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) and cyclic adenosine monophosphate(c AMP) in rat thrombotic model were studied. Through the study of network pharmacology,12 components of aspirin and Trichosanthis Fructus,including hydroxygenkwanin,quercetin and adenosine,were found to show the anti-platelet aggregation and anti-thrombosis mechanisms through9 common protein targets,such as SRC,RAC1,MAPK14,MAPK1,AKT1,and 14 common signaling pathways,such as VEGF signaling pathway. After the intervention with Trichosanthis Fructus pellets combined with aspirin pellets,the vascular endothslia growth factor(VEGF) signaling pathway can be activated to inhibit platelet aggregation and improve vascular endothelial function,and show the anti-platelet aggregation and anti-thrombosis mechanisms,which verify the results of the network pharmacology,and explain the anti-platelet aggregation and anti-thrombotic mechanisms of the combination of Trichosanthis Fructus pellets with aspirin pellets.
6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Aspirin ; pharmacology ; Cyclic AMP ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Fruit ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rats ; Signal Transduction ; Thrombosis ; drug therapy ; Thromboxane B2 ; metabolism ; Trichosanthes ; chemistry

The successful revascularization and reperfusion of ischemia are still associated with high systemic complication rates and severe local tissue injuries. The morality rates after revascularization have been reported to range from 10% to 20% and the amputation rates from 12% to 22%. It is well recognized that the microvasculature is highly sensitive to ischemia-reperfusion (I/R) and that the initial damage of endothelial cells contributes to I/R-induced tissue injury. In an effort to define the mechanisms responsible for reperfusion-induced vascular injury number of in vitro models have been developed to stimulate the responses of endothelial cells to I/R. Because of its simplicity, many investigators have used monolayers of cultured endothelial cells exposed to anoxia and reoxygenation as a model system to minic I/R-induced vascular changes in vivo. The endothelium serves as an important modulator of vascular homeostases by secreting various levels of both thrombotic and antithrombotic agents. One of the important product of endothelial cells, prostaglandin I2 or prostacyclin (PGI2) helps to maintain hemostasis through its involvement in coagulation, platelet activation, leukocyte migration and adhesion, vascular tone regulation and growth control. PGI2 synthesis is a readily quantifiable index of endothelial cell perturbation and thus serves as a marker for the identification of injurious stimuli. Endothelial cells were isolated from human umbilical vein and cultured in M-199 medium plus 20% fetal calf serum. Purity of culture was determined by immunological fluorescent staining of factor VIII related antigen, phase-contrast microscopy. TRK 790 radio-immunoassay kit was used for the measuring of 6-keto-PGF1 alpha released by endothelial cells. The results were as follows: 1) The concentration of PGI(2) released from the cultured endothelial cells was 33.44 +/- 2.26 pg/1 105 cells/mL 2) Incubation of endothelial cells with anoxia and reoxygenation resulted in PGI(2) release of 42.98 +/- 2.29 pg/1x10(5) cells/ml and 62.44 2.11 pg/1 105 cells/ml, respectively. 3) Incubation of endothelial cells with allopurinol (20 mumol/L) decreased the PGI(2) release to 40.68 +/- 2.99 pg/1x10(5) cells/ml. In conclusion, our data showed that the damage of endothelial cells in reoxygenotion group was significantly increased comparing anoxia group (p<0.005) and that allopurinol can inhibit reoxygenation-induced injury of endotheial cells.
6-Ketoprostaglandin F1 alpha ; Allopurinol ; Amputation ; Anoxia ; Endothelial Cells ; Endothelium ; Epoprostenol ; Fibrinolytic Agents ; Hemostasis ; Humans ; Ischemia ; Leukocytes ; Microscopy, Phase-Contrast ; Microvessels ; Morals ; Platelet Activation ; Reperfusion ; Research Personnel ; Umbilical Veins ; Vascular System Injuries ; von Willebrand Factor

BACKGROUNDHypertensive crisis could be found after operation in patients with hypertensive intracerebral hemorrhage (HICH). The aim of this study was to explore the changes and the roles of some vasoactive polypeptides during postoperative hypertensive crisis in patients with HICH.

METHODSA total of 31 patients, who were admitted for craniotomy, were enrolled into this study. After the operation, the patients were divided into three groups. Group I consisted of 9 patients with postoperative hypertensive crisis, and group II was composed of 13 patients without postoperative hypertensive crisis. Nine patients, who denied history of hypertension or HICH, were set as group III. The levels of some vasoactivators in the three groups were measured before and after the operation. The differences in the results among the groups were analyzed using the ANOVA. The data collected before and after the operation in the group I was compared by Wilcoxon test.

RESULTSThe concentration of endothelin in group I was significantly higher than that in group III (P < 0.05). The level of thromboxane A2 and the ratio of thromboxane B2 to 6-keto-PGF1a in group I were significantly higher than those in the other two groups (P < 0.05). In group I, the levels of plasma renin activity, angiotensin II, aldosterone, catecholamine, and endothelin before the operation were significantly higher than those determined after the operation (P > 0.05).

CONCLUSIONSPostoperative hypertensive crisis may be due to the increased thromboxane A2 and relatively inadequate prostacyclin, especially 6-keto-PGF1a. The increased level of endothelin and intraoperative stimulation also play a certain role in the development of postoperative hypertensive crisis.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Aged ; Endothelins ; blood ; Female ; Humans ; Hypertension ; blood ; etiology ; Intracranial Hemorrhage, Hypertensive ; blood ; physiopathology ; surgery ; Male ; Middle Aged ; Postoperative Complications ; blood ; Thromboxane B2 ; blood

To evaluate the changes of 3', 5'-cyclic adenosine monophosphate (cAMP), thromboxane A2(TXA2) and prostacyclin (PGI2) in cerebrospinal fluid (CSF) in the asphyxiated newborn and explore their roles in hypoxic-ischemic brain damage (HIBD). Thirty-six full term newborns were divided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13 with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB2 (TXA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite) in CSF and plasma were measured 36-72 h after birth by RIA, and the concentrations were expressed as nM/L (cAMP), ng/L(TXB2 and 6-keto-PGF1 alpha). The infants were followed-up at 6 and 12 month of age and Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using Bayley Scales of Infant Development (BSID). The CSF cAMP level in moderate-severe HIE group was 8.60 +/- 2.40, significantly lower than that of the mild HIE group (14.83 +/- 2.84) and the control group (24.43 +/- 2.39) (for both P < 0.01). The levels of TXB2 and 6-keto-PGF1 alpha in CFS in the moderate-severe HIE group (206.06 +/- 29.74, 168.47 +/- 23.02, respectively) were significantly higher than in the mild HIE group (83.37 +/- 28.57, 131.42 +/- 16.57, respectively, P < 0.01) and the control group (41.77 +/- 21.58, 86.23 +/- 13.05, respectively, P < 0.01). The level changes of cAMP, TXB2 and 6-keto-PGF1 alpha in plasma in all groups were similar to those in CSF, but no significant difference was found between mild HIE group and the control group (P > 0.05). The follow-up results showed that MDI and PDI of the moderate-severe HIE group were the lowest (84.79 +/- 13.34, 83.50 +/- 13.28, respectively), followed by mild HIE group (102.19 +/- 7.02, 99.94 +/- 9.08, respectively), with the control group being the highest (116.63 +/- 12.08, 116.69 +/- 10.87, respectively). Univariate analysis showed some significant difference (the moderate-severe HIE group vs. the mild HIE group or the control group, P < 0.01; the mild HIE group vs. the control group P < 0.05). The results suggested that the concentration of cAMP, TXA2 and T/K ratio in CSF after neonatal asphyxia might be sensitive markers in evaluating the severity of brain damage in early stage and predicting the future outcome.
6-Ketoprostaglandin F1 alpha ; cerebrospinal fluid ; Asphyxia Neonatorum ; cerebrospinal fluid ; Biomarkers ; Cyclic AMP ; cerebrospinal fluid ; Epoprostenol ; cerebrospinal fluid ; Female ; Follow-Up Studies ; Humans ; Hypoxia-Ischemia, Brain ; cerebrospinal fluid ; Infant, Newborn ; Male ; Thromboxane A2 ; cerebrospinal fluid ; Thromboxane B2 ; cerebrospinal fluid

OBJECTIVETo explore the protective effect and mechanism of ligustrazine (LGT) and propofol (PRO) on peri-operational liver ischemia-reperfusion injury (HIRI).

METHODSThirty-six patients scheduled for hepatic surgery were randomly divided into the control group, the LGT group, the PRO group and the LGT + PRO group, 9 patients in each group. Changes of superoxide dismutase (SOD), lipid peroxide (LPO), ratio of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), alanine aminotransferase (ALT) activity, and the ultrastructure of liver tissue were dynamically observed.

RESULTSCompared with the control group, SOD activity was significantly higher, LPO concentration, TXB2/6-keto-PGF1alpha ratio and ALT value were significantly lower (P < 0.05 and P < 0.01) in the LGT group, the PRO group and the LGT + PRO group during HIRI, with the abnormal changes of hepatic ultrastructure 25 min after reperfusion significantly alleviated in the three treated group.

CONCLUSIONCombination of ligustrazine and propofol shows protective effect on liver by decreasing oxygen free radical level, reducing lipid peroxidation and adjusting TXA2/PGI2 imbalance after hepatic ischemia-reperfusion in patients undergoing hepatic cancer surgery.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Drug Therapy, Combination ; Female ; Humans ; Lipid Peroxides ; blood ; Liver ; blood supply ; Liver Neoplasms ; surgery ; Male ; Middle Aged ; Propofol ; therapeutic use ; Pyrazines ; therapeutic use ; Reperfusion Injury ; prevention & control ; Superoxide Dismutase ; blood

OBJECTIVETo investigate the effects and possible mechanisms of puerarin on the vascular active factors correlated to cerebral vasospasm (CVS) after aneurysm subarachnoid hemorrhage (aSAH).

METHODSFifty-four patients with aSAH were randomly assigned to the puerarin group (30 cases) and the control group (24 cases) by lot. On the basis of routine treatment, the patients in the puerarin group were intravenously dripped with 0.5 g puerarin by adding in 250 mL glucose injection once daily. The injection was given starting from the 3rd day of the disease course, for 14 successive days. The plasma levels of nitric oxide (NO), endothelin-1 (ET-1), thromboxane B, (TXB2), 6-Keto-prostaglandin F1alpha (6-K-PGF1alpha) were compared between the two groups pre- and post-therapy. The incidence of cerebral vasospasm (CVS) was observed using transcranial Doppler (TCD). The Glasgow outcome scale (GOS) were compared at discharge between the two groups.

RESULTSCompared with the control group, the plasma levels of NO, ET-1, and 6-K-PGF1alpha increased in the puerarin group (P < 0. 05), the TXB2 level decreased (P < 0.05), the incidence of CVS decreased (P < 0.05), the mean MCA velocity increased (P < 0.05), and the GOS at discharge increased (P < 0.05).

CONCLUSIONSPuerarin is an effective agent for the prophylaxis and treatment of the CVS in patients after aSAH. Moreover, it can improve the prognosis. The mechanism might be correlated with improving the levels of the vascular active factors, i.e., increasing the plasma levels of NO and PGl2, decreasing TXA, in plasma, increasing the cerebral blood flow, and improving cerebral perfusion.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Aged ; Endothelin-1 ; blood ; Female ; Humans ; Isoflavones ; therapeutic use ; Male ; Middle Aged ; Nitric Oxide ; blood ; Prognosis ; Subarachnoid Hemorrhage ; blood ; complications ; drug therapy ; Thromboxane B2 ; blood ; Vasospasm, Intracranial ; blood ; drug therapy ; etiology