The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

Study Progress in Signaling through Thromboxane A2 Receptors in Platelet and Anti-platelet Drugs / 中国药师

Thromboxane A2 receptors (TPs) widely distribute in different organ systems and localize both on cell membranes and in intracellular structures.TPs are the members of seven-transmembrane G-protein-coupled receptor (GPCR) super family.Historical-ly, the involvement of TPs in platelet functions has received the greatest attention .TPs have the capacity to activate different signaling cascades which regulate platelet shape change , aggregation and secretion response .Currently , anti-platelet drugs primarily act on re-ceptors and /or signaling molecules in activation pathways .The signaling transduction of TPs in platelet contributes to the investigation of the effects of extracts of traditional Chinese medicine on antiplatelet aggregation and the exploration of the action mechanisms .

Effects of Icariin on Partial Vasoactive Substances in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model / 医药导报

Objective To investigate the effects of icariin (ICA) on partial vasoactive substances in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model.Methods Sixty male SD rats were randomly divided into five groups:normal control group,model control group,ICA low-,middle-and high-dose (20,40,80 mg · kg-1 · d-1) group,12 rats in each group.Except for normal control group,the rats were injected with MCT (50 mg · kg-1 · d-1) to establish PAH model.After 1 week MCT-injection,ICA was given by intragastric administration for 3 weeks according to different groups.Mean pulmonary artery pressure (mPAP) was recorded through catheter connected with Power Lab system.Except for normal control group,the right ventricular hypertrophy index (RVHI) was calculated using formula:right ventricle weight/the weight of left ventricle with septum× 100％.The morphology of lung artery was assessed by HE staining.Concentration of angiotensin Ⅱ (Ang Ⅱ),endothelin (ET),prostaglandine F2α(PGF2α),thromboxane A2(TXA2) and prostacyclin (PGI2) in serum was measured by ELISA kit assay.The protein levels of angiotensin converting enzyme (ACE),cyclooxygenase-2 (COX-2) and thromboxane A2 synthetase (TXAS) were analyzed by Western blotting,expression of ACE,COX-2 and TXAS mRNA was measured by real time RT-PCR.Results Compared with the normal control group,mPAP [(48.5±5.2) mmHg] and RVHI (33.3±3.8)％in model control group were significantly increased (P ＜ 0.05),the morphology revealed there was obvious artery remodeling at distal artery,the contents of Ang Ⅱ,PGFA2,TXA2 in serum were elevated,and ACE,COX-2 and TXAS gene expression was up-regulated in rats treated with MCT.ICA (40,80 mg · kg-1 · d-1) treatment significantly attenuated mPAP,RVHI and pulmonary artery remodeling (P ＜ 0.05),and decreased the contents of serum Ang Ⅱ,ET,PGF2β,TXA2,and PGI2,and inhibited the gene expression of ACE,COX-2 and TXAS.Conclusion ICA decreases the contents of AngⅡ,ET,PGI2,PGF2α and TXA2 in the serum of MCT-induced PAH rats,which may be one of the mechanisms underlying ICA inhibiting PAH.

Effect of Different Doses of Oxycodone on Plasma Thromboxane A2, Plasma Endothelin Levels and Immune Function of Patients Underwent Laparoscopic Cholecystectomy / 现代生物医学进展

Objective:To study the effect of different doses of oxycodone on the serum thromboxane A2 (TXA2),plasma endothelin (ET) levels and immune function of patients underwent laparoscopic cholecystectomy.Methods:90 patients of elective laparoscopic cholecystectomy who were treated from August 2013 to August 2016 in our hospital were selected and divided into 3 groups by random number table,with 30 cases in each group.At the beginning of operation,they were given intravenous oxycodone,group A was given 0.1 mg/kg oxycodone,group B was given 0.2 mg/kg oxycodone,group C was given 0.3 mg/kg oxycodone.The changes of hemodynamics,serum TXA2 and ET levels were compared between the three groups at T0 (after admission),T1 (after anesthesia induction),T2 (after intubation),T3 (gallbladder separation),T4 (end of surgery) and the changes of immune function was compared at T0,T5 (postoperative 2h),T6(postoperative 1d),T7 (postoperative 3d);and the extubation time,recovery time,hypotensor,additional analgesics situationin and adverse reactions were recorded.Results:The diastolic pressure (DBP),systolic blood pressure (SBP),heart rate (HR) in three groups at T2,T3 point was significantly higher than T0 point(P＜0.05),the DBP,SBP and HR in the B,C groups were significantly lower than the A group at T2 and T3 point(P＜0.05);the TXA2 in three groups at T2,T3,T4 point was significantly higher than T0 point(P＜0.05),and A group＞B group＞C group,there was significant difference between the two groups (P＜0.05);the ET in three groups at T2,T3 point was significantly higher than T0 point(P＜0.05),the ET in the B,C group was significantly higher than the A group at T2,T3 point(P＜ 0.05);the CD3+,CD4+,CD8+ and CD4+/CD8+ of the three groups at T5 point were significantly lower than that ofT0 point (P＜0.05),the CD3+,CD4+,CD8+ and CD4+/CD8+ in A group were significantly lower than that of B,C group at T5 point (P＜0.05);the extubation time in C group was significantly longer than that of A,B group(P＜0.05);the total incidence of adverse reactions in C group was significantly higher than that the A,B group (P＜0.05).Conclusion:In the laparoscopic cholecystectomy,application of 0.2 mg/kg oxycodone had little effect on hemodynamics,serum TXA2,ET levels and immune function with higher safety.

Effects of traditional Chinese medicine syndrome differentiation quadruple therapy on serum vascular active substance in patients with acute pancreatitis / 中国中西医结合急救杂志

Objective To observe the effects of traditional Chinese medicine (TCM) syndrome differentiation quadruple therapy on serum thromboxane A2 (TXA2), prostacyclin (PGI2) and platelet activating factor (PAF) levels in patients with acute pancreatitis (AP). Methods Ninety patients with AP admitted to the First Affiliated Hospital of Henan University of TCM from January 2016 to March 2017, and they were divided into an observation group and a control group according to the random numbers generated by computer inpatients, 45 cases in each group. The control group was given routine treatment of western medicine, and the observation group was given TCM syndrome differentiation quadruple therapy according to the patient's disease individual situation and on the basis of western medicine treatment. The TCM syndrome differentiation quadruple therapy included the following methods: intragastric administration of TCM decoction [gastrointestinal excess heat syndrome (rhubarb, sodium sulfate, aurantii fructus immaturus, magnolia bark, etc.), damp heat syndrome of liver and gallbladder (radix bupleuri, aurantii fructus immaturus, baical skullcap root, rhubarb, etc.), each group of above agents immersed in water and decocted to make juice 400 mL, once 100 mL taken orally, every 4 hours]; retention enema with TCM decoction [rhubarb, magnolia bark, aurantii fructus immaturus, sodium sulfate (dissolved) etc, each dose of agents forming decoction 400 mL, 200 mL taken for proctoclysis, once every 6 hours]; Chinese medicine package (boswellin, myrrha, dandelion, coptidis rhizoma and so on crushed and mixed with honey, then applied to the body surface of the pancreas and its periphery, 1 dose each time for 4 hours, once a day ); intravenous drip of blood-activating and stasis-resolving TCM (Dengzhanhuasu injection 100 mg added to 5% glucose solution 250 mL for intravenous drip). The times of disappearance of abdominal distension, abdominal pain, and the recovery times of bowel sound, blood amylase, lipase, C-reactive protein (CRP), white blood cell count (WBC) levels to normal were compared between the two groups; the modified CT severity index (MCTSI) score and the changes of serum TXA2, PAF and PGI2 levels were observed before and after treatment in the two groups. Results The abdominal pain and abdominal distension disappearance times in observation group were shorter than those in control group [abdominal pain (days): 5.07±1.88 vs. 6.02±1.89, abdominal distension (days): 3.50±1.49 vs. 4.40±1.53, both P < 0.05]; the recovery times of bowel sounds, WBC, CRP, amylase and lipase to normal were shorter than those of the control group [bowel sounds (days): 4.05±1.79 vs. 5.00±1.55, WBC (days): 3.93±1.49 vs. 5.98±2.90, CRP (days): 6.17±2.46 vs. 7.92±2.84, blood amylase (days): 3.5 (3.0, 5.0) vs. 5.0 (3.0, 5.5), lipase (days): 5.0 (3.0, 7.0) vs. 6.5 (5.0, 9.0), all P <0.05]; the scores of MCTSI in the two groups were lower than those before treatment and the degree of decrease in the observation group was more significant than that in the control group [2 (0, 4) vs. 4 (0, 6), P < 0.05]. The TXA2 and PAF levels of the two groups were significantly lower than those before treatment and the level of PGI2 was significantly higher than that before treatment; after treatment for 3 days, the differences between the two groups showed statistical significance and on the 7th day after treatment, the degrees of improvement in observation group were more obvious than those of the control group [TXA2 (ng/L): 276.81±31.48 vs. 345.42±47.27, PAF (ng/L): 72.65±17.61 vs. 89.77±15.59, PGI2 (ng/L): 104.43±18.67 vs. 94.37±17.91, all P < 0.05]; on the 14th day after treatment, the values of the two groups were very close and there were no statistically significant differences (all P >0.05). Conclusions The TCM differentiation syndrome quadruple therapy for treatment of AP is beneficial to the disappearance of clinical symptoms of patients with different syndromes, recovery of abnormal signs and improvement of laboratory indexes, and its early use can significantly reduce the serum levels of TXA2, PAF and increase the level of PGI2 in patients with AP.

Effects of traditional Chinese medicine syndrome differentiation quadruple therapy on serum vascular active substance in patients with acute pancreatitis / 中国中西医结合急救杂志

Objective To observe the effects of traditional Chinese medicine (TCM) syndrome differentiation quadruple therapy on serum thromboxane A2 (TXA2), prostacyclin (PGI2) and platelet activating factor (PAF) levels in patients with acute pancreatitis (AP). Methods Ninety patients with AP admitted to the First Affiliated Hospital of Henan University of TCM from January 2016 to March 2017, and they were divided into an observation group and a control group according to the random numbers generated by computer inpatients, 45 cases in each group. The control group was given routine treatment of western medicine, and the observation group was given TCM syndrome differentiation quadruple therapy according to the patient's disease individual situation and on the basis of western medicine treatment. The TCM syndrome differentiation quadruple therapy included the following methods: intragastric administration of TCM decoction [gastrointestinal excess heat syndrome (rhubarb, sodium sulfate, aurantii fructus immaturus, magnolia bark, etc.), damp heat syndrome of liver and gallbladder (radix bupleuri, aurantii fructus immaturus, baical skullcap root, rhubarb, etc.), each group of above agents immersed in water and decocted to make juice 400 mL, once 100 mL taken orally, every 4 hours]; retention enema with TCM decoction [rhubarb, magnolia bark, aurantii fructus immaturus, sodium sulfate (dissolved) etc, each dose of agents forming decoction 400 mL, 200 mL taken for proctoclysis, once every 6 hours]; Chinese medicine package (boswellin, myrrha, dandelion, coptidis rhizoma and so on crushed and mixed with honey, then applied to the body surface of the pancreas and its periphery, 1 dose each time for 4 hours, once a day ); intravenous drip of blood-activating and stasis-resolving TCM (Dengzhanhuasu injection 100 mg added to 5% glucose solution 250 mL for intravenous drip). The times of disappearance of abdominal distension, abdominal pain, and the recovery times of bowel sound, blood amylase, lipase, C-reactive protein (CRP), white blood cell count (WBC) levels to normal were compared between the two groups; the modified CT severity index (MCTSI) score and the changes of serum TXA2, PAF and PGI2 levels were observed before and after treatment in the two groups. Results The abdominal pain and abdominal distension disappearance times in observation group were shorter than those in control group [abdominal pain (days): 5.07±1.88 vs. 6.02±1.89, abdominal distension (days): 3.50±1.49 vs. 4.40±1.53, both P < 0.05]; the recovery times of bowel sounds, WBC, CRP, amylase and lipase to normal were shorter than those of the control group [bowel sounds (days): 4.05±1.79 vs. 5.00±1.55, WBC (days): 3.93±1.49 vs. 5.98±2.90, CRP (days): 6.17±2.46 vs. 7.92±2.84, blood amylase (days): 3.5 (3.0, 5.0) vs. 5.0 (3.0, 5.5), lipase (days): 5.0 (3.0, 7.0) vs. 6.5 (5.0, 9.0), all P <0.05]; the scores of MCTSI in the two groups were lower than those before treatment and the degree of decrease in the observation group was more significant than that in the control group [2 (0, 4) vs. 4 (0, 6), P < 0.05]. The TXA2 and PAF levels of the two groups were significantly lower than those before treatment and the level of PGI2 was significantly higher than that before treatment; after treatment for 3 days, the differences between the two groups showed statistical significance and on the 7th day after treatment, the degrees of improvement in observation group were more obvious than those of the control group [TXA2 (ng/L): 276.81±31.48 vs. 345.42±47.27, PAF (ng/L): 72.65±17.61 vs. 89.77±15.59, PGI2 (ng/L): 104.43±18.67 vs. 94.37±17.91, all P < 0.05]; on the 14th day after treatment, the values of the two groups were very close and there were no statistically significant differences (all P >0.05). Conclusions The TCM differentiation syndrome quadruple therapy for treatment of AP is beneficial to the disappearance of clinical symptoms of patients with different syndromes, recovery of abnormal signs and improvement of laboratory indexes, and its early use can significantly reduce the serum levels of TXA2, PAF and increase the level of PGI2 in patients with AP.

Influence of Thromboxane A₂ on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

BACKGROUND AND OBJECTIVES: Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels play an important role in myocardial protection. We examined the effects of thromboxane A₂ on the regulation of K(ATP) channel activity in single ventricular myocytes. SUBJECTS AND METHODS: Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at -60 mV holding potential during the perfusion of an ATP-free K-5 solution. RESULTS: In the excised inside-out patches, the thromboxane A₂ analog, U46619, decreased the K(ATP) channel activity in a dose-dependent manner; however, the thromboxane A₂ receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced K(ATP) channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced K(ATP) channel activity. CONCLUSION: Thromboxane A₂ may inhibit K(ATP) channel activity, and may have a harmful effect on ischemic myocardium.

Influence of Thromboxane A₂ on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

BACKGROUND AND OBJECTIVES: Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels play an important role in myocardial protection. We examined the effects of thromboxane A₂ on the regulation of K(ATP) channel activity in single ventricular myocytes. SUBJECTS AND METHODS: Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at -60 mV holding potential during the perfusion of an ATP-free K-5 solution. RESULTS: In the excised inside-out patches, the thromboxane A₂ analog, U46619, decreased the K(ATP) channel activity in a dose-dependent manner; however, the thromboxane A₂ receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced K(ATP) channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced K(ATP) channel activity. CONCLUSION: Thromboxane A₂ may inhibit K(ATP) channel activity, and may have a harmful effect on ischemic myocardium.

Efficacy of Seratrodast, a Thromboxane A2 Receptor Inhibitor in a Double Blind Comparative Clinical Trial with Monteluklast.

Aims: To assess the comparative efficacy, safety and tolerability of seratrodast versus montelukast in controlling mild to moderate asthma in adult patients. Study Design: Randomized, comparative, double blind, double dummy, multi-center, parallel group, non inferiority study. Methods: Patients (n=205) with mild to moderate asthma continuing on the lowest dose of inhaled corticosteroid were recruited from 3 different centers across India. Patients were randomly assigned to receive either seratrodast 80 mg (n=103) or montelukast 10 mg (n=102) once daily for 28 days. The treatments were compared for improvement from the baseline values, as per the changes in asthma symptom score (wheezing, shortness of breath, expectoration, cough and chest tightness), lung function parameters (PEF, FVC and FEV1), sputum and mucociliary parameters [fucose, eosinophil cationic protein (ECP) and albumin]. Results: Seratrodast and montelukast showed improvement in the clinical parameters of asthma as well as in the lung function tests and sputum parameters from baseline. Both the treatments significantly increased mean values of PEF, FVC and FEV1 from the baseline after a 4 week treatment but seratrodast produced significantly greater improvement in PEF (0.416 L/s, P=.01). Moreover, there was significantly more reduction in expectoration score (P=.01), sputum concentrations of ECP (P<.001) and albumin (P<.001) in seratrodast group, signifying improvement in asthma condition. The two treatment groups had similar tolerability profiles. Mild increase in hepatic enzymes was seen in both the groups with no clinical significance. No serious adverse events were observed during the study. Conclusions: Seratrodast, a Thromboxane A2 receptor antagonist, was found to be better in the improvement of PEF, reduction in expectoration, ECP and albumin levels as compared to montelukast. Seratrodast can be recommended as a controller medication in mild to moderate asthma.

Daño a células endoteliales en cultivo inducido por el isoprostano 8-iso-PGF2a / Damage to cultured endothelial cells induced by isoprostane 8-iso PGF2

INTRODUCCIÓN: el endotelio vascular posee un papel esencial en los procesos asociados a la enfermedad cardiovascular. Existe estrecha relación entre el desbalance redox de estas células y la aparición y evolución de estas enfermedades. Entre los marcadores de daño oxidativo a los lípidos de membranas se encuentra el isoprostano 8-iso-PGF2a, que aumenta en estos pacientes. OBJETIVO: evaluar el efecto del isoprostano 8-iso-PGF2a sobre células endoteliales en cultivo y la protección con la proteína de estrés térmico a-cristalina. MÉTODOS: se cultivaron células endoteliales de la línea H5V y se evaluó el efecto del isoprostano 8-iso-PGF2a y del análogo del tromboxano A2, U46619, sobre la supervivencia celular. Se evaluó el efecto protector de la proteína de estrés térmico a-cristalina a través de la incubación de los cultivos con 1 mg/ml de la proteína previo a la inducción del daño con los compuestos en estudio. RESULTADOS: la supervivencia celular disminuyó proporcional al aumento de la concentración del isoprostano y del U46619. La a-cristalina aumentó la supervivencia celular en un 20 % al preincubar los cultivos sometidos al efecto de ambos compuestos. CONCLUSIONES: el isoprostano 8-iso-PGF2a, además, de ser un marcador de daño oxidativo puede ser considerado un inductor directo de daño a las células del endotelio vascular, efecto mediado a través, de la generación de tromboxano A2 o la activación de su receptor. La proteína de estrés térmico a-cristalina, añadida de forma exógena, puede considerarse un protector endotelial.

INTRODUCTION: the vascular endothelium plays an essential role in processes associated with cardiovascular disease. There is a close relationship between redox imbalance in these cells and the appearance and evolution of such diseases. Increased isoprostane 8-iso PGF2 is among the markers of oxidative damage to membrane lipids in these patients. OBJECTIVE: evaluate the effect of isoprostane 8-iso PGF2 on cultured endothelial cells and the protection provided by -crystallin heat-shock stress protein. METHODS: endothelial cells from line H5V were cultured to evaluate the effect of isoprostane 8-iso PGF2 and thromboxane A2 analog U46619 on cell survival. An evaluation was conducted of the protective effect of -crystallin heat-shock stress protein by incubation of the cultures with 1 mg/ml of the protein prior to damage induction with the study compounds. RESULTS: cell survival decreased as isoprostane and U46619 concentration increased. -Crystallin increased cell survival by 20% upon preincubation of the cultures subjected to both compounds. CONCLUSIONS: besides being an oxidative damage marker, isoprostane 8-iso PGF2 may be considered a direct inducer of damage to vascular endothelial cells. This effect is mediated by the generation of thromboxane A2 or the activation of its receptor. Added exogenously, -crystallin heat-shock stress protein may be considered to be an endothelial protector.

Thromboxane A2 receptor induces proliferation of rheumatoid arthritis synovial cells by up-regulation of cyclooxygenase-2 / 中国病理生理杂志

AIM:To examine the effects of thromboxane A 2 receptor ( TXA2 R) , the downstream product of cy-clooxygenase-2 (COX-2), on the proliferative ability and COX-2 expression in rheumatoid arthritis (RA) synovial cells. METHODS:The effects of TXA2 R antagonist SQ29548 and agonist U46619 on the proliferation of RA synovial cell line MH7A were detected by MTS cell proliferation assay , and their effects on COX-2 mRNA expression in MH7A cells were al-so examined by real-time PCR.In addition, the possible effect of U46619 on the proliferation of MH7A cells, when COX-2 was knocked down by siRNA , was determined by BrdU cell proliferation assay .RESULTS:SQ29548 inhibited the cell proliferation and the mRNA level of COX-2 while U46619 enhanced them.Moreover, U46619 reconstitute the proliferative ability of MH7A cells to some extent that inhibited by COX-2 siRNA.CONCLUSION: In RA synovial cells, TXA2R is able to control COX-2 expression, while it also mediates the effects of COX-2, suggesting that TXA2R might be an ideal candidate for RA treatment .

A study on correlation between thromboxane A2 receptor gene polymorphism and aspirin resistance / 中国中西医结合急救杂志

Objective To investigate the association between thromboxane A2 receptor(TXA2R)gene C795T, T924C,G1686A,rs2271875,rs768963 polymorphisms and aspirin resistance(AR)in Chinese Han population. Methods 168 in-patients with cerebral infarction who had been given aspirin from Zhejiang Provincial Taizhou Central Hospital from October 2009 to May 2013 were enrolled. The platelet aggregation rate was conducted by optical method. The inspections of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C)were conducted by enzymatic colorimetry,whereas blood glucose was tested by hexokinase method. The genotypes of three exons loci C795T,T924C,G1686A and two promoters loci rs2271875,rs768963 polymorphisms in TXA2R gene were detected by the polymerase chain reaction-ligase detection reaction(PCR-LDR)technique. The patients were divided into aspirin sensitive group(AS group,139 cases) and AR group(39 cases)according to the aspirin sensitive degree. The differences between two groups in age, smoking,serum TG,TC,HDL-C,LDL-C,concentration of blood glucose and blood pressure(systolic pressure, diastolic pressure)were compared,and in the mean time,the differences between two groups of TXA2R C795T, T924C,G1686A,rs2271875,rs768963 genotype distribution were also compared. Results AR group had higher incidences of cigarette smoking〔89.7%(35/39)vs. 69.8%(90/129)〕and high blood sugar(mmol/L:8.086±2.785 vs 5.631±1.662,P0.05). It was shown that there was no correlation between TXA2R gene polymorphism and AR. Conclusion The patients with smoking,high concentration of blood glucose have a higher incidence of AR,no correlation between TXA2R gene polymorphism and AR is found.

COX2-PGI2/TXA2 signal pathway involved in protective mechanism of PDTC pretreatment against global cerebral ischemia reperfusion rat hippocampus injury / 中国药理学通报

Aim To investigate the effects and mecha-nism of nuclear factor-κ B inhibitor, PDTC, on global cerebral ischemia reperfusion ( GCIR ) rat hippocam-pus. Methods Forty-eight adult male Sprague-Daw-ley rats were randomly divided into one control group receiving sham operation and three experimental groups all receiving global cerebral ischemia for 20 min. In PDTC 100 mg·kg-1 group ( P100 ) and PDTC 200 mg ·kg-1 group ( P200 ) , PDTC 100 mg · kg-1 or PDTC 200 mg·kg-1 was injected ip one hour before ischemi-a respectively. Spatial learning and memory function of rats were tested using Morris water maze. HE staining was employed to observe pathological changes of hipp-ocampal neurons. Expression of COX2 was measured by Western blot, and the content of PGI2 and TXA2 in rat hippocampus was detected by enzyme-linked immu-nosorbent assay. Results A significant increase of es-cape latency was observed in GCIR group compared to the sham operation group(P<0.05). PDTC 100 mg· kg-1 and PDTC 200 mg · kg-1 significantly reduced escape latency ( P <0.05 ) and histopathological injury in CA1 region of hippocampus. PDTC 100 mg · kg-1 and PDTC 200 mg · kg-1 also reduced COX2 expres-sion, PGI2 content, TXA2 content and PGI2/TXA2 . Conclusion Pretreatment with PDTC can protect hip-pocampus from GCIR injury through inhibition of COX2 expression and PGI2/TXA2 .

Expression of C3a, C5a, TXA2, LT in pulmonary injury of infant open heart surgery improved with the modified ultrafiltration technique / 中国医师杂志

Objective To study the mechanism of pulmonary injury and protective effect of modified ultrafiltration on lung function in infant open heart surgery.Methods According to the wishes of parents,40 cases of congenital heart disease were divided into without modified ultrafiltration control group (C) and modified ultrafiltration group (M),and parents signed informed consent.The cardiopulmonary bypass (CPB) was used without ultrafiltration in Group C,while with modified ultrafiltration in group M.The pneumodynamic parameters and C3a,C5a,TXA2,LT were measured at specific time points.Results The static pulmonary compliance (Cstat) and oxygen index (OI) were lower,and alveolar-arteria oxygen difference (AaDO2) was higher after CPB in the two groups(P ＜ 0.05).At T3,T4 and T5 time points,the Cstat and OI in Group M was higher than that in Group C; AaDO2 in Group M was lower than that in Group C (P ＜0.05).The levels of C3a and C5a were lower after CPB in the two groups; levels of TXA2,LT were higher after CPB in the C groups.At T2,T3,T4 and T5 time points,the TXA2 and LT in Group M were lower than that in Group C(P ＜0.05).Conclusions The pulmonary injury in pediatric open heart surgery may be concerned with the the alexin(C3a,C5a) activation and I/R.The level of C3a and C5a was considered earlier index of inflammatory reaction and pulmonary injury.Modified ultrafiltration improves pulmonary function due to elevating coloid osmotic pressure and degrading the plasma level of TXA2,LT.

Requirement of Pretone by Thromboxane A2 for Hypoxic Pulmonary Vasoconstriction in Precision-cut Lung Slices of Rat

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, K+ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the K+ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine (EC50, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholine-induced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

Effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To investigate the effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion (I/R) in rats. Methods Fifty healthy male Wistar rats weighing 250-280 g were randomly divided into 5 groups (n = 10 each) : sham operation group (group S) , I/R group, sevoflurane preconditioning group (group Spr), sevoflurane postconditioning group (group Spo)and combination of sevoflurane preconditioning and postconditioning group (group Spr + po). Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion in anesthetized rats. In group S the anterior descending branch was only exposed but not ligated. Group Spr received 15 min inhalation of 2.5 % sevoflurane and 15 min wash-out 30 min before ischemia. Group Spo received 5 min inhalation of 2.5% sevoflurane 1 min before reperfusion. Arterial blood samples were taken at 2 h of reperfusion for determination of the levels of MB isoenzyme of creatine kinase (CK-MB) , lactate dehydrogenase (LDH) , cardiac troponin I (cTnI), thromboxane B2(TXB2), and 6-keto-prostaglandin (6-keto-PGF1α) and platelet maximum aggregation rate. TXB2/6-keto-PGF1α ratio was calculated. The myocardial tissues were taken for microscopic examination. Mitochondria] injury was assessed by using Flameng score and stereology (Specific surface, δ and Numerical density on area, NA) .Results Compared with group S, the levels of CK-MB, LDH, cTnI, TXE2 and 6-ketoPGF1α, TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly increased, while δ and NA were significantly decreased in group I/R (P < 0.05 or 0.01) . The levels of CK-MB,LDH and cTnI, TXB2/6-keto-PGF1α ratio and Flameng score were significantly lower, and 6-keto-PGF1α level, δand NA were significantly higher in Spr and Spo groups than in group I/R ( P < 0.05 or 0.01) . The levels of CKMB, LDH, cTnI and TXB2 , TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly lower and 6-keto-PGF1α level,δ and NA were significantly higher in group Spr + po than in Spr and Spo groups(P < 0.05). Conclusion Sevoflurane preconditioning-postconditioning can reduce myocardial I/R injury through inhibiting the release of thromboxane A2 and promoting the release of prostaglandin I2 in rats.

Thromboxane A2 Synthetase Inhibitor Plus Low Dose Aspirin : Can It Be a Salvage Treatment in Acute Stroke Beyond Thrombolytic Time Window

OBJECTIVE: There is no proven regimen to reduce the severity of stroke in patients with acute cerebral infarction presenting beyond the thrombolytic time window. Ozagrel sodium, a selective thromboxane A2 synthetase inhibitor, has been known to suppress the development of infarction. The antiplatelet effect is improved when aspirin is used together with a thromboxane synthetase inhibitor. METHODS: Patients with non-cardiogenic acute ischemic stroke who were not eligible for thrombolysis were randomly assigned to two groups; one group received ozagrel sodium plus 100 mg of aspirin (group 1, n=43) and the other 100 mg of aspirin alone (group 2, n=43). Demographic data, cardiovascular risk factors, initial stroke severity [National Institute of Health Stroke Scale (NIHSS) and motor strength scale] and stroke subtypes were analyzed in each group. Clinical outcomes were analyzed by NIHSS and motor strength scale at 14 days after the onset of stroke. RESULTS: There were no significant differences in the mean age, gender proportion, the prevalence of cardiovascular risk factors, stroke subtypes, and baseline neurological severity between the two groups. However, the clinical outcome for group 1 was much better at 14 days after the onset of stroke compared to group 2 (NIHSS score, p=0.007, Motor strength scale score, p<0.001). There was one case of hemorrhagic transformation in group 1, but there was no statistically significant difference in bleeding tendency between two groups. CONCLUSION: In this preliminary study, thromboxane A2 synthetase inhibitor plus a low dose of aspirin seems to be safe and has a favorable outcome compared to aspirin alone in patients with acute ischemic stroke who presented beyond the thrombolytic time window.

Association of thromboxane A2 receptor gene polymorphism with wheezing episode after RSV infection in children / 中国综合临床

Objective To investigate the potential role of respiratory syncytial virus (RSV) in wheezing episode in children, and to assess the association of the thromboxane A2 receptor gene (TBXA2R) T924C polymorphism with wheezing after RSV infection. Methods From may to december in 2008, one hundred and twenty-five asthmatic children who were suffering from acute episode were recruited as cases and 49 healthy children as controls in our Polymerase chain reactions-Restriction fragment length polymorphism (PCR-RELP) techniques were used to detect the TBXA2R SNP. RSV IgM and IgG were measured by ELISA. Results RSV specific antibody was positive in 57 asthmatic patients (45.6% ,57/125) and 8 controls (16.33% ,8/49) ,with significant difference between the two groups ( χ2 = 12. 890, P = 0. age asthmatic group and 76. 92% (30/39) in the <3 years of age asthmatic group, with significant difference between the two groups (χ2 = 22. 420, P = 0. 000 ). The genotypes distribution in the asthmatic patients was significantly different from that in the controls(χ2 = 5. 346, P = 0. 021). The frequency of TC and CC genotypes in the cases was significantly higher than that in the control group. The allele frequencies of T and C allele were similar in the two groups ( χ2 =2.660, P=0.103). Conclusions RSV infection was one of the factors that associated with asthma acute episode, especially in children younger than 3 years. The TC,CC genotypes increase the chance of wheezing in children infected by RSV.

Study of batroxobin on improving microcirculation in patients with severe acute pancreatitis / 中国医师进修杂志

Objective To explore the effects of batroxobin on the microcirculation of patients with severe acute pancreatitis (SAP). Methods A total of 38 patients with SAP were randomly divided into group A (21 cases) and group B (17 cases). Patients in group A were treated with routine method andpatients in greup B were treated with routine method plus batroxobin injection. Another 18 normal individuals were used as control. The levels of plasma endothelin (ET), thromboxane B_2 (TXB_2) and 6-keto-PGF_(1α)were measured by radioimmunoassay. At the same time, the ratio of TXB_2/6-keto-PGF_(1α) was observed. The Balthazar CT and APACHE Ⅱ scores were monitored and compared between group A and group B. Results The levels of plasma 6-keto-PGF_(1α) were significantly higher while the levels of plasma ET, TXB_2 and the ratio of TXB_2/6-keto-PGF_(1α) were significantly lower in group B at 6 days after admission [(129.3 ± 12.9) ng/L, (93.8 ± 9.9) ng/L, (254.4 ± 24.9) ng/L and 1.83 ± 0.31]as compared with those in group B on admission [(98.9 ± 10.7) ng/L, (140.3 ± 13.1) ng/L, (311.4 ± 31.5) ng/L and 3.16 ± 0.54]and group A at 6 days after admission [(108.2 ± 11.6) ng/L, (120.3 ± 11.4) ng/L, (308.5 ± 31.1) ng/L and 2.84 ± 0.43](P < 0.05). The Balthazar CT and APACHE Ⅱ scores in group B at 6 days after admission were significantly lower than those in group B on admission and group A at 6 days after admission (P< 0.05 or < 0.01). Conclusion Batroxobin is an effective way to improve the microcirculation in SAP.

Thromboxane A2 modulates migration, proliferation, and differentiation of adipose tissue-derived mesenchymal stem cells

Prostanoid metabolites are key mediators in inflammatory responses, and accumulating evidence suggests that mesenchymal stem cells (MSCs) can be recruited to injured or inflamed tissues. In the present study, we investigated whether prostanoid metabolites can regulate migration, proliferation, and differentiation potentials of MSCs. We demonstrated herein that the stable thromboxane A2 (TxA2) mimetic U46619 strongly stimulated migration and proliferation of human adipose tissue-derived MSCs (hADSCs). Furthermore, U46619 treatment increased expression of alpha-smooth muscle actin (alpha-SMA), a smooth muscle marker, in hADSCs, suggesting differentiation of hADSCs into smooth muscle-like cells. U46619 activated ERK and p38 MAPK, and pretreatment of the cells with the MEK inhibitor U0126 or the p38 MAPK inhibitor SB202190 abrogated the U46619-induced migration, proliferation, and alpha-SMA expression. These results suggest that TxA2 plays a key role in the migration, proliferation, and differentiation of hADSCs into smooth muscle-like cells through signaling mechanisms involving ERK and p38 MAPK.