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

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World Journal of Gastroenterology 2005年第2期11卷 232-236页

作者： Chi-JenChu Ching-ChinHsiao Teh-FangWang Cho-YuChan Fa-YauhLee Full-YoungChang Yi-ChouChen Hui-ChunHuang Sun-SangWang Shou-DongLee DivisionofGastroenterology DepartmentofMedicineTaipeiVeteransGeneralHospitalTaipeiTaiwanChina ArmedForcesSungshanHospital TaipeiTaiwanChina DepartmentofMedicalResearchandEducation TaipeiVeteransGeneralHospitalTaipeiTaiwanChina//NationalYang-MingUniversitySchoolofMedicineTaipeiTaiwanChina DivisionofGastroenterology DepartmentofMedicineTaipeiVeteransGeneralHospitalTaipeiTaiwanChina//DivisionofGeneralMedicineDepartmentofMedicineTaipeiVeteransGeneralHospitalTaipeiTaiwanChina TaipeiMunicipalGan-DauHospital TaipeiTaiwanChina//NationalYang-MingUniversitySchoolofMedicineTaipeiTaiwanChina DivisionofGastroenterology DepartmentofMedicineTaipeiVeteransGeneralHospitalTaipeiTaiwanChina//NationalYang-MingUniversitySchoolofMedicineTaipeiTaiwanChina

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 intraperitoneal injection of TAA (350 mg/(kg·d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg·d), n = 20) or normal 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%, P0.05), 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 live

关键词： Hepatic Encephalopathy Fulminant hepatic failure prostacyclin Indomethacin

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Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin

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Acta Pharmacologica Sinica 2005年第9期26卷 1063-1068页

作者： He HU~1 Xiao-xue ZHANG~1 Yin-ye WANG~(1,2) Shi-zhong CHEN~31 Department of Molecular and Cellular Pharmacology Beijing University Beijing 100083,China 3 Department of Natural Medicinal Chemistry,School of Pharmaceutical Sciences,Peking University Beijing 100083,China DepartmentofMolecularandCellularPharmacology BeijingUniversityBeijing100083China

Aim:To study the effect of honokiol on arterial thrombosis and endothelial ***:Rabbit platelet aggregation was performed with Born's turbid *** was produced by the endothelial injury stimulated with electric *** aortic endothelial cells（RAEC）were cultured and cell viability was assessedusing the MTT *** oxide（NO）concentrations in serum-free media ofRAEC were determined using the kinetic cadmium-reduction *** stablemetabolite prostacyclin was measured in serum-free media of RAEC ***:Honokiol（37.6-376 lamol/L）decreased rabbit plate-let aggregation in vitro in a concentration-dependent manner,while intravenouslyinjection of honokiol（0.12-12 μg/kg）significantly inhibited rabbit platelet aggre-gation induced by collagen ex *** the electrical current-stimulated carotidthrombosis model in rats,honokiol（5-50 μg/kg,iv）prolonged the thrombus oc-clusion time in a does-dependent *** vitro honokiol（0.376-37.6 μmol/L）effectively protected cultured RAEC against oxidized low density lipoprotein（ox-LDL ）injury,and significantly increased 6-keto-PGF1α（the stable metabolite ofprostacyclin）in serum-free media of *** also increased NO level inRAEC serum-free medium at a lower concentration range（0.0376-0.376 μmol/L）,but honokiol 3.76 μmol/L decreased NO ***:Honokiol is a potentarterial thrombosis *** cell protection and the stimulation ofprostacyclin release may be its main anti-thrombosis *** ofNO release in endothelial cells may play a role,but it is not a key factor.

关键词： honokiol platelet aggregation thrombosis cultured cells endothelium prostacyclin nitric oxide

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RELATION OF MALIGNANT TUMOR TO prostacyclin AND THROMBOXANE

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Chinese Journal of Cancer Research 1995年第1期7卷 75-78页

作者：谈亚英王彬刘富光周连妹刘俊 Department of Nuclear Medicine The 2nd Affiliated Hospital Zhejiang Medical University Hangzhou

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 *** 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,*** 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 *** study also revealed that the size of tumor,metastasis and histological classification had no obvious relation to PGs.

关键词： Proetaglandin prostacyclin Thromboxane Arachidonic acid

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EFFECTS OF MODULATED LDLs ON THE RELEASE OF ENDOTHELIN-1 AND prostacyclin BY ENDOTHELIAL CELLS IN CULTURE

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Academic Journal of Xi'an Jiaotong University 2001年第1期13卷 1-4,8页

作者：徐仓宝 Lab. for Atherosclerosis Research Med. Sch. of Xi'an Jiaotong Univ. Xi'an 710061 China

Objective To study the releases of endothelin-1 and prostacyclin by endothelial cells in culture and to elucidate how these releases were influenced by smoke-treated low density lipoprotein. Methods We exposed en- dothelial cell cultures to native or oxidized low density lipoproteins,low density lipoproteins treated by dimethylsul- foxide-soluble particles from cigarette smoke or dimethylsulfoxide alones. The release of endothelin-1 was assayed by bioassay and the release of prostacyclin was assayed by radioimmunoassay. Results Low density lipoproteins treated by smoke significantly increased the release or endothelin-1 (Pprostacyclin (P< 0.02) by endothelial cells in culture, contrast to native or dimethylsulfoxide-treated lipoproteins. Conclusion The main part or vasoconstrictor activity in conditioned medium from bovine aortic EC is endothelin-1.

关键词： endothelial cells low density lipoproteins smoke endothelin-1 prostacyclin

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Mechanism of overproduction of plasma prostacyclin in portal hypertensive rats

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Chinese Medical Journal 1998年第12期 8-11页

作者：曹晖吴志勇周健焦哲陈治平邝耀麟

Abstract Objective To evaluate the role of increased portal pressure and portosystemic shunting in elevated level of prostacyclin (PGI 2) in portal hypertension. Methods Thirty six male Sprague Dawley rats were divided into four groups: prehepatic portal hypertension (PHPH, 8 rats), intrahepatic portal hypertension (IHPH, 9), end to side portacaval shunt (PCS, 8), and sham operated controls (SO, 11). Two weeks after surgery, free portal pressure (FPP) was measured; systemic and splanchnic hemodynamics was studied by radioactive microsphere technique and blood sample from the femoral artery was obtained to measure the level of plasma 6 keto PGF 1 α with radio immunoassay. Results The FPP (mmHg) in IHPH, PHPH, PCS and SO rats was 13.10±1.02, 12.10±1.52, 3.0±0.82 and 6.86±0.69, respectively. The value of FPP was significantly increased in IHPH, PHPH rats and significantly decreased in PCS rats when compared to SO rats. Cardiac index (CI) and portal venous inflow (PVI) were in the order of PCS>PHPH>IHPH>SO rats. Portosystemic shunting (PSS) in PCS, PHPH, IHPH was 99.7±0.29%, 76.02±20.62% and 30.34±10.18%, respectively. The concentrations of plasma 6 keto PGF 1α (ng/ml) in PHPH, IHPH, PCS and SO rats were 6.93±2.43, 5.09±2.27, 2.36±1.01 and 1.56±0.61, respectively. The concentrations of plasma PGI 2 in PHPH, IHPH and PCS rats were significantly higher than those in SO rats. Furthermore, the concentrations of plasma PGI 2 in PHPH and IHPH rats were also significantly higher than those in PCS rats. Moreover, a closed positive correlation existed between plasma PGI 2 and FPP (r=0.67, P<0.001). Conclusions The results of the present study suggest that the elevated PGI 2 in portal hypertension is mainly due to the overproduction of PGI 2 in vascular epithelium cells induced by increased portal pressure, whereas portosystemic shunting and liver dysfunction play a secondary role. In addition, the results of this study do not support that P

关键词： overproduction plasma rats portal prostacyclin hypertensive Mechanism

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

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Pharmacology & Pharmacy 2011年第4期2卷 306-314页

作者： Mai Hazekawa Yoshiki Sakai Miyako Yoshida Tamami Haraguchi Takahiro Uchida 不详

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.

关键词： ONO-1301 prostacyclin Agonist Neuroprotection Cerebral Ischemia Astrocytes

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Changes of Thromboxane and prostacyclin after Smoke Inhalation Injury in Goats

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Military Medical Research 1988年第1期 41-46页

作者：黄跃生黎鳌杨宗城陈发明 Research Institute of Burns Third Military Medical College Chongqing

Thirteen goats with chronic lung lymph fistula were inflicted withsmoke inhalation *** A(TXAin terms of thromboxane BorTXB)and prostacyclin(PGlin terms of 6-keto-prostaglandin For6-keto-PGFx)in plasma,lung lymph and lung tissue were measured withradioimmunoassay(RIA).Extravascular lung water(EVLW),lung lymph flow(QL),the ratio of protein contents between lung lymph and plasma(LIP),hemodynamic parameters,blood gases,platelet and leukocyte counts were ***,QL and L/P increased significantly at the 1st hour,reachedtheir peak values at the 2nd hour,then declined gradually and remained at a levelover the baseline at the 6th hour after *** PGlalso increasedmarkedly and *** of TXAand TXA/PGIratio were in parallel withthose of EVLW,QL and LIP both in degree and in length of *** is possiblethat the increased TXAand TXA/PGIratio might participate in the formationof permeability pulmonary edema through direct injury and for chemical mediatorsreleased by platelet and leukocyte aggregations promoted by *** addition,TXAmight also play a role in the early elevation of pulmonary arterial pressure.

关键词： goat smoke inhalation injury thromboxane A2 prostacyclin extravascular lung water lung lymph flow

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Ligustrizini　promotes　prostacyclin　release　from　cultured　human　umbilical　cord　vein　endothelial　cells

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Journal of Medical Colleges of PLA(China) 1995年第4期10卷 313-316页

作者：何红兵仲剑平马素珍

The endothelial cells derived from human umbilical cord vein were treated with 200 μg/ml ligustrizini. The inhibrtory rate of platelet aggregation of the supernatant from the cultured endothelial cells treated with l... 详细信息

关键词： ligustrizini prostacyclin endothelial cells

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Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome

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World Journal of Critical Care Medicine 2017年第1期6卷 74-78页

作者： Martin Albert Daniel Corsilli David R Williamson Marc Brosseau Patrick Bellemare Stéphane Delisle Anne QN Nguyen France Varin Departments of Intensive Care and Medicine Hopital du Sacré-Coeur de Montréal Research Center Université de Montréal Department of Intensive Care Centre Hospitalier Universitaire de Montréal Université de Montréal Department of Pharmacy Université de Montréal Hopital du Sacré-Coeur de Montréal Research Center Department of Respiratory Care Hopital du Sacré-Coeur de Hopital du Sacré-Coeur de Montréal Research Center Université de Montréal

AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of i NO(20 ppm) or nebulized epoprostenol(10 μg/mL) was done in all patients. Thereafter, inhaled milrinone(1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide(iN O) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen(PaO_2) were recorded before and after each inhaled *** The majority of ARDS were of pulmonary cause(n = 13) and pneumonia(n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass(n = 2), smoke inhalation injury(n = 1), thoracic trauma and pulmonary contusions(n = 2) and aspiration(n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and i NO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO 2 from baseline was 8.8 mmH g [interquartile range(IQR) = 16.3], 6.0 mm Hg(IQR = 18.4), 6 mm Hg(IQR = 15.8) and 9.2 mm Hg(IQR = 20.2) respectively with i NO, epoprostenol, inhaled milrinone, and i NO added to milrinone. Only i NO and the combination of inhaled milrinone and i NO had a statistically significant effect on PaO 2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milr

关键词： Inhaled milrinone Nitric oxide Pulmonary hypertension Hypoxemia Acute respiratory distress syndrome prostacyclin

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前列环素(prostacyclin)的药理研究近况

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国外医学.内分泌学分册 1982年第4期02卷 186-190页

作者：翁福海天津医学院药理教研室

自从Moncada等1976发现前列环素（prostacyclin,PGI2）以来,很多学者研究了前列环素的药理生理作用,发现它是一个很强的抑制血小板聚集及扩张血管的活性物质。对肾脏水盐代谢影响及与肾素-血管紧张素系统关系方面都有研究探讨。前列环... 详细信息

自从Moncada等1976发现前列环素（prostacyclin,PGI2）以来,很多学者研究了前列环素的药理生理作用,发现它是一个很强的抑制血小板聚集及扩张血管的活性物质。对肾脏水盐代谢影响及与肾素-血管紧张素系统关系方面都有研究探讨。前列环素对心血管系统的作用国内已有综述,有关前列环素抗血小板聚集作用也有报道。本文仅对前列环素药理研究近况作一回顾简述。

关键词：前列环素血管壁 prostacyclin 血小板聚集药理研究 PGI 近况

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