Diet Rich in Saturated Fat Decreases the Ratio of Thromboxane/prostacyclin in Healthy Men

Objective To investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane 62 (TXB2) and 6-keto prostaglandin F la (PGF la) in 27 healthy free-living male subjects aged 30 to 55 years. Methods It 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. Results Serum 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 lα (P<0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2. Conclusions Diet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

Effects of thromboxane and prostacyclin imbalance on hemodynamics and hemorrheology in severely burn patients

Fifty-seven bum patients were dosdy observed for 28 d postburn.In general,plasma levelof thromboxane B2（TXB2）,6-keto-PGFlx and TXB2/6-keto-PGFlx ratio all rose up abruptly tothe peak in the first half day after burns and then declined gradually.However the patterns of theirchanges were different:6-keto-PGFlx returned to the control level in the 2nd day postburn,remained in a higher level than the control even in the 5th day postburn,and the increase ofTXB2/6-keto-PGFlα ratio was especially pronounced in the first 3 d postbum.It was also shownthat the changes of hemodynamics and hemorrheology occurred simultaneously with the imbalanceof thromboxane and prcstacyclin in the early postburn stage.The extent of the imbalance accordedwith the severity of hemodynamical and hemorrheological changes and was closely correlated withthe changes with the stroke volume,cardiac output,systemic vascular resistance,circulatory plateletaggregate ratio,platelet count and blood vinery.These findings suggest that the imbalance be-tween thromboxane and prostacyclin plays an important role in the changes of hemodynamics andhemorrheology in severe burn cases.

RELATION OF MALIGNANT TUMOR TO PROSTACYCLIN AND THROMBOXANE

The level of 6-keto-PGF1αand thromboxane B2(TXB2) in Plasma was determined with radioimmunoassay in 58 normal subjects and 92 Patients with various cancers(including lung,hepatic,gastric,esophageal and pancreatic carcinoma).The results showed that 6-keto-PGF1α.In plasma was 10.21±2.75 Pg/ml,and TXB2 146.03±37.31 Pg/ml in normal individuals,the ratio of 6-keto-PGF1α to TXB2 was 0.07;while in cancer Patients 6-keto-PGF1αwas 27.5±16.9 Pg/ml and TXB2 315.4±173.4 Pg/ml, the ratio of 6-keto-PGF1αto TXB2 was 0.08.The values of 6-keto-PGF1αand TXB2 in plasma of cancer patients were 2.69 folds and 2.16 folds higher than that of the two groups,respectively.The difference between the two groups was statistically significant(P<0.01).It indicates that the synthesis and release of PGI2 and TXA2 of cancer tissues increases greatly as compared to the normals.The study also revealed that the size of tumor,metastasis and histological classification had no obvious relation to PGs.

Effect of Intra-arachnoid Space Perfusion on Thromboxane A and Prostacycline in Experimental Spinal Cord Injury

In order to understand the relation between TXA2- PGI2 and secondary trauma and the effect of intra-arachnoid perfusion of dexamethasone and verapamil on alteration of TXA,-PGI, following spinal cord injury, TXB2 and 6-keto-PGFconcentration and pathological changes in injured site 1, 2, 4 and 6 h after injury were studied using a rabbit spinal cord injury model by Allen's weight drop method.

Changes of thromboxane and prostacyclin in the pathogenesis of multiple organ failure in severe burns

Fifty-seven severely burned patients were divided into 2 groups:16 withmultiple organ failure（MOF）,and 41 without MOF.It was found that the levelof thromboxane B2（TXB2）and the ratio between TXB2 and 6-keto-prostaglandinF1α(TBX2/6-keto-PGF1α)in plasma and in visceral tissues were increased and re-mained significantly high in the first 5～7 d postburn in patients with MOF but notso in those without MOF.The circulatory platelet aggregate ratio（CPAR）wasmarkedly decreased in the same period in MOF group.Myocardial enzymes（CPK,LDH,and GOT）were markedly increased in the first 3d and remainedsignificantly high within 7 d postburn.Degeneration,structural destruction,edema,hemorrhage and thrombosis were revealed in cardiac,pulmonary,renal andhepatic tissues succumbing to functional failure.Thirteen out of the 16 cases de-veloped MOF during the 3rd to 7th day posthurn and 11 died in that period.These findings substantiate that persistent increase of thromboxane andthromboxane/prostacyclin ratio is closely related to the origin and development ofMOF after burn injury.

Neuroprotective Effect of a Prostacyclin Agonist (ONO-1301) with Thromboxane Synthase Inhibitory Activity in Rats Subjected to Cerebral Ischemia

ONO-1301 has been developed as a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. In the present study, we investigated the cerebroprotective effect of ONO-1301 on post-ischemic injury induced by cerebral ischemia in rats. ONO-1301 (1 and 10 mg/kg) was administrated orally at reperfusion and then twice a day for 42 days. The cell damage induced by cerebral ischemia in the hippocampal CA1 was evaluated using both Nissl staining and proliferating cell nuclear antigen (PCNA) staining on the 42 days after cerebral ischemia. Activated astrocytes were evaluated using immunofluorescence staining with GFAP on the 42 days after cerebral ischemia. Spatial learning was assessed using a Morris water maze (MWM) task on the 56 days (i.e. after a 14 days washout period). ONO-1301- treated rats (1 and 10 mg/kg) significantly improved cell death in the hippocampal CA1, the number of PCNA-positive cells and astrocyte activation. The spatial learning of ONO-1301-treated rats compared with vehicle- treated rats in the MWM task. These results suggest that repeated treatment with oral ONO-1301 could prevent or limit post-ischemic brain damage. In particular, treatment with ONO-1301 within 7 days after ischemia is most effective to improve ischemic damage.

Platelet thromboxane(11-dehydro-Thromboxane B_2) and aspirin response in patients with diabetes and coronary artery disease

Aspirin(ASA) irreversibly inhibits platelet cyclooxygenase-1(COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes(DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2(11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls(P = 0.024): female subjects(DM and controls) had 50.9% higher baseline 11dhTxB2 than males(P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM(71.7%) and controls(75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders(ASA "resistant") in DM than in controls(14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome(ACS) patients was 28.6 and 28.7%, in spite of a significant(81.6%) inhibition of urinary 11dhTxB2(P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.

Associations between thromboxane A synthase 1 gene polymorphisms and the risk of ischemic stroke in a Chinese Han population

Thromboxane A synthase 1 （TBXAS1） catalyses the synthesis of thromboxane A2 （TXA2）, which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls （P 〈 0.01 and P = 0.02）. Furthermore, compared with the GG ＋ GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke （odds ratio （OR） = 1.80, 95% confidence interval （CI）： 1.16–2.79, P 〈 0.01）. Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke （OR = 1.94,95% CI ： 1.13–3.33, P = 0.02）. The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis （OR = 1.49, 95% CI： 1.10–2.00, P 〈 0.01）. These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry （registration number： ChiCTR-COC-17013559）.

Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation

瞄准：为了调查起作用的仙子，氮的氧化物变化(没有) 并且 endothelin (et ) ， thromboxane A2 (TXA2 ) 和在在结束阶段肝疾病病人的肝移植期间的前列腺素(PGI2 ) 。方法：有经历肝移植的结束阶段肝硬化的 27 个病人在这未来的研究被注册。血样品在五个不同外科的阶段从优异静脉被获得。硝酸盐和亚硝酸根的血浆集中决心反映血浆没有层次。ET-1,6-keto-PGF1 高山的血浆层次哈并且 thromboxane B2 (TXB2 ) ，后者二分别地是 PGI2 和 TXA2 的稳定的代谢物，被测量。结果：没有水平在脉管的跨 clamping 以后显著地减少了并且在灌注以后在 30 min 显著地增加了。当在在夹钳以后并且在灌注以后的 30 min 的 ET 层次显著地被提高时。NO/ET 的比率在脉管的跨 clamping 以后并且在外科的结束在 30 min 显著地减少了。PGI2 水平和 TXA2 在肝移植期间比基线水平显著地高，但是 TXA2/PGI2 的比率在夹钳以后在 30 min 显著地减少了。结论：NO/ET 和 TXA2/PGI2 在肝移植期间变化。尽管精确机制仍然保持未知，他们可以在许多肝的病理学起一个作用移植, 移植物, 移植片相关的过程。

Inhibition of Cyclooxygenase and Thromboxane Synthetase on Oxygen Delivery and Utilization in Acute Respiratory Failure Canine

The puapose of this study was to evaluate the effects of cyclooxygenase inhibitor (Ibuprofen)and thromboxane synthetase inhibitor (OKY-046) on oxygen metabolism in acute respiratory failure.Intratracheal instillation of hydrochloric acid was produced in 18 dogs, six dogs were pretreated with ibuprofen (IBU), six dogs with OKY-046 (OKY),and the remaindere used as control (CTR). After acid aspiration oxygen delivery (DO_2) fell in all groups as a results of decreased PaO_2 and cardiac output.However, oxygen consumption (VO_2)was maintained in all animals by the end of experiments except in CTR group. Arterial oxygen content maintained at baseline level throughout the experiments in IBU group. Meanwhile a significantly decreased mixed venous oxygen tension was found in OKY group after acid challenge. Liner regression of _vO_2 and DO_2 was confirmed in both CTR and OKY group. However,the dependent relationship between VO_2 and DO_2 was not identified in IBU group, which may indicate that the body oxygen metabolism was maintained rather well in acute rcspiratory failure dogs treated with ibuproten.

Effects of procainamide on adenosine diphosphate-induced platelet aggregation and thromboxane B_2 production in rabbits in vitro

Turbidimetry and radioimmunoassay were used to study the effects of procainamide (PA ) onadenosine diphosphate (ADP)-induced rabbit platelet aggregation and thromboxane B2 (TXB2) production invitro. PA 8. 5--544. 0 μmol L-1 inhibited ADP-induced platelet aggregation and TXB2 production, and theinhibition rates were 26. 7% -- 66. 7 % and 21. 4 % -- 70. 1 %, respectively. There was positive correlation between PA concentration and its efficiency in inhibiting the platelet aggregation and TXB2 production, and alsobetween the inhibition rates of platelet aggregation and that of TXB2 production. The three linear equationsand main parameters were The results indicate that PA could significantly inhibit ADP--induced platelet aggregation and TXB2 production in rabbits.

倍他司汀联合氢溴酸山莨菪碱治疗眩晕症的疗效

目的研究倍他司汀联合氢溴酸山莨菪碱治疗眩晕症患者的疗效、安全性以及对患者血流动力学、血清血小板活化因子(platelet activated factor,PAF)和血栓素B(2 thromboxane B2,TXB2)的影响。方法将80例眩晕症患者用随机数字表法分为倍他司汀组和对照组,各40例。对照组采用氢溴酸山莨菪碱治疗,倍他司汀组在对照组治疗的基础上加用倍他司汀治疗,治疗周期为14 d。治疗后通过眩晕症状评分简化量表(vertigo symptom score-short form,VSS-SF)和眩晕残障程度评定量表(dizziness handicap inventory,DHI)评估患者的眩晕程度;通过经颅多普勒(transcranial doppler,TCD)结果评价患者左椎动脉、右椎动脉和椎基底动脉的血流情况;测定患者血清PAF和TXB2水平;统计治疗后总有效率;观察2组患者不良反应(呕吐、过敏反应、睡眠障碍、肝功能异常和凝血功能异常)的发生情况。结果治疗后,倍他司汀组患者的总有效率高于对照组(P<0.05);倍他司汀组的VSS-SF、DHI量表评分均低于对照组(P<0.05),患者左椎动脉、右椎动脉和椎基底动脉血流情况均优于对照组(P<0.05),患者PAF、TXB2水平均低于对照组(P<0.05);2组不良反应发生率比较差异无统计学意义。结论倍他司汀联合氢溴酸山莨菪碱治疗眩晕症有较好的临床效果,可以改善患者的眩晕症状及眩晕程度,降低患者的炎性因子水平,对于患者脑部血流动力学有较好的改善作用。

Comparing the efficacy and safety of low,medium,and high dosages of selexipag for treating pulmonary hypertension:A systematic review and meta-analysis

Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.

Apigenin is an anoikis sensitizer with strong anti-metastatic properties in experimental breast cancer

Loss of susceptibility to anoikis signals is a crucial step in metastasis.Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management.In this study,we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods.Among 19 tested dietary phytochemicals,the best results were obtained with apigenin,a natural component of celery.Phenotypically,apigenin sensitized breast cancer cells to anoikis,lowered the number of circulating tumor cells,and protected against breast cancer metastasis to lung in mice.Mechanistically,we demonstrated that the thromboxane A_(2)(TXA_(2))-TXA_(2)receptor(TP)axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway.Blockage of TXA_(2)signaling up-regulated p53 as well as its target gene p21,caused a G1 phase arrest,and finally led to apoptosis in breast cancer cells.TXA_(2)level was positively correlated with breast cancer cell anoikis rate,and apigenin significantly inhibited TXA_(2)biosynthesis in vitro and in vivo.Collectively,we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer,and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.

通络护肾汤对早期2型糖尿病肾病患者微循环指标影响

目的:观察通络护肾汤对早期2型糖尿病肾病患者微循环指标的影响。方法:选取2022-2023年就诊江西省中西医结合医院内分泌科确诊糖尿病肾病患者100例,分为试验组和对照组,每组各50例。两组均予以降糖常规治疗,对照组在常规治疗基础上加用厄贝沙坦片,试验组在对照组基础上加用通络护肾汤。比较治疗前后各组患者尿素氮(BUN)、血肌酐(CREA)、尿微量白蛋白、内皮素-1(ET-1)、血栓素B2(TXB2)的变化。结果:治疗后,两组患者的BUN、CREA、尿微量蛋白、ET-1、TXB2均较治疗前下降,但试验组较对照组下降显著,差异具有统计学意义(P<0.05)。结论:通络护肾汤可有效缓解早期2型糖尿病肾病患者微循环,降低尿蛋白,有保护肾功能的作用。

电针治疗对腰椎间盘突出症患者血清炎症因子和血浆血栓素B2水平的影响

目的:分析电针治疗对腰椎间盘突出症患者血清炎症因子和血浆血栓素B2水平的影响。方法:选取2021年10月—2023年10月沭阳中山医院骨外科收治的110例腰椎间盘突出症患者作为研究对象,依据不同的治疗方案分为常规组和电针组,各55例。常规组实施常规中医针灸治疗,电针组实施电针治疗。比较两组的血清炎症因子、血浆血栓素B2水平及疼痛程度[视觉模拟评分法(VAS)]。结果:治疗前,两组VAS评分、血浆血栓素B2、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平比较,差异无统计学意义(P>0.05);治疗后,两组VAS评分、血浆血栓素B2、IL-6、TNF-α水平均低于治疗前,且电针组低于常规组,差异有统计学意义(P<0.05)。结论:与常规中医针灸治疗相比较,电针治疗腰椎间盘突出症效果较好。

脑脊液中TXB2、S100B水平与高血压脑出血患者预后的相关性

目的探究脑脊液中血栓素B2(thromboxane B2,TXB2)、S100钙结合蛋白B(S100 calcium-binding protein B,S100B)水平与高血压脑出血患者预后的相关性。方法选取2020年5月至2023年5月西安市长安医院急诊收治的高血压脑出血患者96例,均行微创血肿清除术治疗,收集所有患者的病历资料,检测患者术后24 h脑脊液中的TXB2、S100B水平。依据患者术后28 d预后分为预后良好组和预后不良组。分析高血压脑出血预后的影响因素,评价脑脊液中TXB2、S100B水平对高血压脑出血患者预后的预测效能。采用χ^(2)检验、独立样本t检验,影响因素的分析采用多因素logistic逐步回归模型。结果术后28 d,96例高血压脑出血患者中预后良好68例(70.83%),预后不良28例(29.17%)。两组性别、年龄、体重指数等一般资料比较,差异均无统计学意义(均P>0.05);预后良好组美国国立卫生研究院卒中量表(NIHSS)评分、中线移位占比及脑脊液TXB2、S100B水平均低于预后不良组[(15.34±2.61)分比(20.18±3.32)分、19.12%(13/68)比39.29%(11/28)、(156.04±17.31)ng/L比(190.35±18.29)ng/L、(1.72±0.34)μg/L比(1.93±0.47)μg/L],差异均有统计学意义(均P<0.05)。NIHSS评分(OR=3.691,95%CI 1.262~10.799)、中线移位(OR=3.425,95%CI 1.171~10.019)、脑脊液TXB2(OR=5.675,95%CI 1.939~16.602)及S100B(OR=4.486,95%CI 1.533~13.125)是高血压脑出血预后的危险因素(均P<0.05)。脑脊液中TXB2、S100B单一及联合预测高血压脑出血患者预后的灵敏度分别为0.764、0.727、0.799,特异度分别为0.641、0.703、0.782,曲线下面积分别为0.731、0.705、0.823。结论脑脊液中TXB2、S100B水平的变化与高血压脑出血患者预后有关,且两者联合检测对高血压脑出血患者预后的预测效能良好。

急性脑梗死患者rt-PA静脉溶栓后脑出血转化与血清TXB2、sICAM-1、PTX3水平的相关性研究

目的探讨血清血栓素B2(TXB2)、可溶性细胞间黏附分子-1(sICAM-1)、正五聚体蛋白3(PTX3)水平变化对急性脑梗死(ACI)患者重组组织型纤溶酶原激活物(rt-PA)静脉溶栓后脑出血转化的影响。方法选取本院收治的82例ACI患者为研究对象,rt-PA静脉溶栓后24 h行CT检查,依据是否发生脑出血转化将其分为转化组和非转化组。分析溶栓后脑出血转化的相关影响因素及溶栓后12 h血清TXB2、sICAM-1、PTX3对脑出血转化的预测价值。结果82例患者中,20例发生脑出血转化,62例未发生脑出血转化。转化组的溶栓前美国国立卫生研究院卒中量表(NIHSS)评分、总胆固醇、纤维蛋白原水平高于非转化组(P<0.05)。溶栓后12、24 h,非转化组的血清TXB2、sICAM-1、PTX3水平低于转化组(P<0.05)。Logistic回归分析结果显示,溶栓前NIHSS评分、TXB2、sICAM-1、PTX3为溶栓后脑出血转化的相关危险因素(P<0.05)。血清TXB2、sICAM-1、PTX3联合预测脑出血转化的曲线下面积(AUC)大于单项预测(P<0.05)。结论溶栓前NIHSS评分及血清TXB2、sICAM-1、PTX3为ACI患者接受rt-PA静脉溶栓后发生脑出血转化的危险因素,而血清TXB-2、sICAM-1、PTX3联合检测对脑出血转化具有较高的预测效能。

Prostacyclin decreases splanchnic vascular contractility in cirrhotic rats

BACKGROUND： Prostacyclin has been shown to increase portal hypertension, but the mechanism is unclear. This study aimed to investigate whether the overproduction of prostacyclin（PGI2） in cirrhosis participates in the splanchnic vascular hyporesponsiveness to vasoconstrictors in cirrhotic rats.METHODS： Cirrhotic model was created by subcutaneous injection of 60% carbon tetrachloride（CCl4） corn oil solution combined with intermittent drinking of 5% alcohol, and agematched rats served as controls. The isolated third-generation mesenteric arterioles were used to examine the contractile response to norepinephrine. The changes in vascular diameter were observed under a microscope imaging device. The plasma concentration of 6-ketone-prostaglandin F1α（6-keto-PGF1α, a stable metabolite of PGI2） was tested via enzyme immunoassays and the expression of cyclooxygenase（COX） in mesenteric arteries was detected by Western blotting.RESULTS： In parallel with the increase of plasma 6-ketoPGF1α, the contractile response of arterioles from cirrhotic rats to norepinephrine was significantly impaired compared with that from controls. Inhibition of PGI2 or protein kinase A with indomethacin or Rp-adenosine 3＇, 5＇-cyclic monophosphothioate（Rp-cAMPS） partially reversed the vascular hypo-contractile response to norepinephrine in arterioles from cirrhotic rats.Indomethacin significantly decreased the plasma 6-keto-PGF1α.Furthermore, indomethacin significantly attenuated the effect of Rp-cAMPS on arterioles from cirrhotic rats. COX-1 expression was up-regulated in mesenteric arteries from cirrhotic rats,whereas COX-2 was not detectable in the mesenteric arteries from both cirrhotic and control rats.CONCLUSION： Enhanced COX-1 expression in cirrhotic rats resulted in elevated PGI2 production which partially contributedto the splanchnic vascular hyporesponsiveness to a vasoconstrictor via the protein kinase A pathway.

Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy.Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure.METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by were divided into two groups to receive intraperitoneal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α(TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay.RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P＜0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S:438±102 vs841±145 counts/30 min, P＜0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-α (indomethacin vsN/S: 22±5 vs 10±1 pg/mL, P＜0.05)and lower plasma levels of 6-keto-PGF1α (P＜0.001), but not total bilirubin or creatinine (P＞0.05), as compared with rats treated with N/S.CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.