Intraportal perfusion of prostaglandin E1 attenuates hepatic postischaemic microcirculatory impairments in rats

BACKGROUND: The efficacy of intraportal perfusion with prostaglandin E1(PGE1) in decreasing postischaemic hepatic microcirculatory damage was studied in rats. METHODS: An extrahepatic portosystemic shunt was created by attaching the spleen to a subcutaneous site on the left lateral wall of the abdomen in male Wistar rats weighing between 200 and 350 g. Four weeks later, when the shunt was mature, the portal vein and hepatic artery were occluded for 60 min. The animals were divided into the following three groups according to the type of intraportal perfusion during the ischaemic phase: group 1 consisted of untreated animals; group 2, animals perfused with lactated Ringer's solution; and group 3, animals perfused with PGE1 (0.1 microg/kg per min). The hepatic microcirculation was observed under an inverted intravital microscope after the injection of fluorescent dyes to label leucocytes and damaged cells 30 and 60 min after reperfusion. The liver was removed 60 min after reperfusion and stained immunohistochemically using 1A29, an anti-rat intercellular adhesion molecule-1 (ICAM-1) antibody. RESULTS: The leucocyte velocity during reperfusion was lowest in group 1 and highest in group 3. Of the three groups, group 3 showed the least leucocyte adhesion to the sinusoidal walls and terminal venules, the lowest damaged cell count and the lowest ICAM-1 expression on the sinusoidal walls. CONCLUSION: The results of this study suggest that hepatic perfusion with PGE1 markedly alleviates microcirculatory damage associated with ischaemia and reperfusion through the inhibition of leucocyte-endothelium interactions.     

Protective effects of endothelin-1 on acute pancreatitis in rats

Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-1 (100 pmol/kg/hr), cerulein (5 µg/kg/hr), or cerulein plus endothelin-1 for 3.5 hr. In another experiment, cerulein or cerulein plus BQ-123 (3 mg/kg/hr) was infused. Infusion of cerulein caused hyperamylasemia and pancreatic edema. Endothelin-1, when infused with cerulein, decreased the extent of pancreatic edema with a significant increase in the pancreatic dry- to wet-weight ratio. Histological changes induced by cerulein were markedly attenuated when endothelin-1 was given with cerulein. In contrast, endothelin-receptor blockade with BQ-123 further augmented pancreatic edema caused by cerulein. The extent of inflammatory cell infiltration was greater when BQ-123 was given with cerulein. Endothelin-1 or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-1 has protective effects on experimental acute pancreatitis.Supported by a grant from the Ministry of Education, Japan (No. B-04454330).     

Tiaprofenic acid inhibits mucosal prostaglandin E2 synthesis without delaying experimental gastric ulcer healing

Increasing evidence suggests that non-steroidal anti-inflammatory drugs (NSAID) differ in gastrotoxicity. This study aimed to compare the effects of a short-acting NSAID, tiaprofenic acid, with indomethacin on experimental gastric ulcer healing in a rat model. Similar anti-inflammatory and prostaglandin-inhibitory doses of indomethacin (1mg/kg) and tiaprofenic acid (2mg/kg) were administered to rats with acetic acid-induced ulcers. After 2 weeks treatment, rats were killed and ulcer size determined. In addition, histological sections of ulcers were assessed for ulcer contraction and mucosal regeneration. The degree of inhibition of prostagiandin E₂ (PGE₂) synthesis was 72% at 2h after tiaprofenic acid and 64% at 2h after indomethacin administration, respectively. Rats treated with indomethacin for 2 weeks had significantly larger ulcers, both macroscopically and microscopically, than controls. Rats treated with tiaprofenic acid for 2 weeks had ulcers of a similar size to those of controls. Indomethacin-treated ulcers showed a failure in mucosal regeneration. Tiaprofenic acid-treated ulcers had significantly more regeneration than indomethacin-treated ulcers. We conclude that tiaprofenic acid inhibits mucosal prostaglandin levels but does not inhibit experimental gastric ulcer healing. These findings suggest that inhibition of PGE₂ synthesis is not the only factor in generating gastrotoxicity and that a shift to low gastrotoxic NSAID may be clinically worthwhile.     

Protective effects of MCP-1 inhibitor on a rat model of severe acute pancreatitis

BACKGROUND:Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis.This study aimed to establish a rat model of severe acute pancreatitis(SAP) for investigating monocyte chemotactic protein-1(MCP-1) expression in the pathogenesis of the disease.We assessed the effects of the inhibitor of MCP-1,Bindarit,on SAP and explored the mechanisms underlying SAP. METHODS:Seventy-two Sprague-Dawley rats were randomly divided into a saline control group(group S),an SAP group (group P),and...     

Jejunal release of prostaglandin E2 in Crohn's disease: Relation to disease activity and first-degree relatives

Patients with Crohn's disease of the distal ileum show increased permeability to hyaluronan and increased release of histamine and complement components in uninvolved parts of the proximal jejunum. These abnormalities are related to disease activity, and are not found in first-degree relatives. Increased synthesis of prostaglandins has been observed in inflamed areas of the intestine in active Crohn's disease. Our purpose was to measure luminal prostaglandin release in patients with active and inactive Crohn's disease and their first-degree relatives. Twenty-four patients with Crohn's disease of the distal ileum (10 in remission and 12 with inflammatory activity) and 17 of their first-degree relatives were included and compared with healthy control subjects (n= 39). Ten centimetres of the proximal jejunum was isolated between balloons as described previously and perfused with a balanced electrolyte glucose-containing solution. Luminal concentrations of PGE₂ and albumin were measured and their luminal release was calculated. Luminal release of PGE₂ was significantly higher in patients with Crohn's disease than in control subjects [69.7 ± 11.5 and 34.0±4.7 pg/cm per h (3.7±0.6 and 1.8±0.3 ng/L), respectively, P <0.01]. The PGE₂ levels, however, were not positively correlated to disease activity. Furthermore, there was a modest, but significant increase in luminal PGE₂ in first-degree relatives [53.6±7.0 pg/cm per h (2.9±0.4 ng/L), P <0.05]. These changes were not accompanied by significant changes in luminal permeation of albumin. The stimulated jejunal synthesis of prostaglandins observed in patients with Crohn's disease and to some extent in their relatives may constitute a response to altered genetic mucosal characteristics.     

The effects of a prostaglandin E1 analogue, misoprostol, on gastric mucosal blood volume index and haemoglobin oxygenation in humans

A double-blind placebo-controlled parallel design study was conducted in 12 healthy male volunteers to examine the effects of misoprostol, a newly synthesized prostaglandin E₁ analogue, on gastric mucosal haemodynamics in human. The indices of mucosal blood volume (expressed as ΔEr) and mucosal blood haemoglobin oxygenation (Hb-SO₂) were measured at 20 locations in the stomach prior to and after administration of misoprostol or its placebo using reflectance spectrophotometry during endoscopy. It was found that after misoprostol administration, mucosal blood volume was increased by approximately 10–25% throughout the stomach without any significant change in mucosal blood Hb-SO₂. Administration of placebo produced no significant change in these parameters. The results suggest that misoprostol has the potential to accelerate healing of gastric ulcers by increasing the gastric mucosal blood volume and oxygenation in addition to its gastric acid antisecretory activity.     

16, 16-dimethyl prostaglandin E2 modulates aflatoxin B1-induced injury of rat hepatocytes in primary culture: Possible role of cAMP

The hepatocellular cytoprotective effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), an analogue of PGE2, were investigated using primary cultures of rat hepatocytes and aflatoxin B1 as the hepatotoxin. Lactic dehydrogenase (LDH) release by hepatocytes was used as an index of hepatotoxicity. When aflatoxin-treated hepatocytes were co-cultured with 16,16-dmPGE2 (0.01-0.5 micrograms/mL) LDH release was significantly reduced and ultrastructural changes of hepatocellular injury were markedly diminished. The magnitude of the cytoprotective effect was not dependent on the concentration of the prostaglandin over the range tested. A significant cytoprotective effect was also induced when hepatocellular cyclic AMP (cAMP) levels were increased by the addition of dibutyl-cAMP. In contrast to 16,16-dmPGE2, PGF2 alpha Tromethamine, an analogue of PGF2 alpha, which does not stimulate cAMP, induced insignificant changes in cytoprotection. These findings indicate that only a low concentration of 16,16-dmPGE2 (> or = 0.01 micrograms/mL) is necessary to induce a maximal hepatocellular cytoprotective effect and suggest that this effect may be dependent on activation of cAMP.     

Duodenal mucosal histology and histochemistry in active, treated and healed duodenal ulcer: Correlation with duodenal prostaglandin E2 production

We investigated whether impaired duodenal mucosal prostaglandin E₂ (PGE₂) production previously observed in duodenal ulcer (DU) was a primary pathophysiological abnormality or secondary to mucosal architectural changes that accompany ulceration. One hundred patients were studied: at endoscopy, paired duodenal biopsies were taken in patients with normal endoscopies and from the ulcer edge or scar and background mucosa in active or healed DU. One of the pair of biopsies was used to estimate PGE₂ synthesis ability, the other was processed for histology and histochemistry. The following features graded: goblet cell numbers and staining with Periodic acid-Schiff reagent (PAS), epithelial staining with PAS, villous atrophy, columnar cell height, inflammatory cell infiltrate and micro-erosions and gastric metaplasia taken as a whole. Patients were found to have normal endoscopy (n= 31), active untreated DU (n= 20), active DU on treatment with either cimetidine or ranitidine (n= 13), healed DU on maintenance treatment (n= 27) and healed DU off treatment (n= 9). Active duodenal ulceration was found to be associated with decreased numbers of goblet cells, loss and blunting of villi, increased columnar cell height, increased epithelial cell PAS staining and with gastric metaplasia. After healing, only villous blunting remained. These changes were present, but less marked, at sites removed from the ulcer and were not apparent in the patient groups with healed ulcers. A strong correlation between overall gastric metaplasia and epithelial cell PAS staining and the reduced ability to synthesize PGE₂ (P < 0.001) was only apparent when biopsies from all patients were grouped together, but not within individual patient subgroups. There was no consistent correlation between PGE₂ generation and individual parameters of pathological change in the duodenum. We conclude that, although inflammatory and mucosal changes may contribute, the evidence suggests that the impaired PGE₂ generation in DU disease is, to a large extent, independent of histological and histochemical features.     

Effect of nizatidine and ranitidine on 24 hour intragastric pH, pepsin, prostaglandin E2 and serum gastrin concentrations in healthy volunteers

In order to achieve possible greater therapeutic efficacy, ranitidine 300 mg bid (R₂) may be given rather than 300 mg qhs (R₁), or nizatidine 300 mg bid (N₂) may be given rather than 300 mg qhs (N₁). A randomized placebo-controlled crossover study was performed in six healthy volunteers (four males, two females) who ranged in age from 23 to 43 years, comparing R₁ R₂, N₁, and N₂ versus placebo (P), measuring 24 h intragastric pH by the aspiration technique, gastric juice pepsin and prostaglandin E₂ (PGE₂) concentrations, as well as serum gastrin concentrations. In all treatment groups, 24-h intragastric pH was higher than with P; the 24 h and daytime (0800–2200 h) pH was higher with N₂ than with N₁ but not with R₂ versus R₁. The percentage pH ≥ 3 was greater with N₂ than with N₁ during the daytime. Night-time (2200–0800 h) and 24 h pepsin concentrations were higher in R₂ than in R₁, were similar in N₁ and N₂, and were lower in these treatment groups than in P. The gastric juice PGE₂ concentration at night-time, but not at daytime, was increased in the four treatment groups compared with P. Despite the higher pH values at night-time in the treatment groups, the night-time concentrations of serum gastrin were unchanged, and yet during the daytime the higher values of pH were associated with increased gastrin concentrations when R₂ or N₂ were given, but not with R₁ and N₂. There was a negative correlation between intragastric juice pH and pepsin concentration during the daytime, and a positive correlation between pH and PGE₂ concentration during the night-time. The slopes and y-axis intercepts between pH and pepsin or PGE₂, concentrations differed between the placebo and the treatment groups, suggesting that these H₂-receptor antagonists may have an effect on lowering pepsin and raising PGE₂ concentrations in addition to their effects on pH. As the percentage of time over the 24 h period and night-time periods when the pH was greater than 3 was not different between ranitidine and nizatidine, the two regimens will likely have similar clinical efficacy.     

Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate-induced pancreatitis

Abstract The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasaemia, high amylase activity in ascitic fluid, hyperendotoxaemia and a high serum level of fibrin degradation products (FDP) and redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. Sodium taurocholate injection into the pancreatico-biliary duct also caused the bacterial growth in the pancreas. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and Shiomarin was significantly more protective than E3123 therapy alone.
These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis.     

Changes in the proteome of human bronchial epithelial cells following stimulation with leucotriene E4 and transforming growth factor-β1

Background and objective: Activated bronchial epithelial cells exert considerable potential to maintain a microenvironment in the airway wall that promotes airway inflammation and remodelling. Cysteinyl leucotrienes (CysLT) and transforming growth factor‐β₁ (TGF‐β₁) are both increased in asthmatic airways and may influence the pathophysiology of disease. However, the consequences of activation of bronchial epithelial cells by these mediators are not fully understood. A proteomic‐based approach was used to characterize the inflammatory pathways in bronchial epithelial cells after stimulation with CysLT and TGF‐β₁. Methods: Human bronchial epithelial cells (BEAS‐2B) were stimulated with 1 ng/mL TGF‐β₁ and 50 nmol/L leucotriene E₄ (LTE₄) for 48 h and whole‐cell lysates were subjected to two‐dimensional gel electrophoresis. Proteins showing statistically significant differential expression were identified by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and database searching. Results: Stimulation with LTE₄ increased the expression of three proteins and five proteins showed decreased expression. Of the latter group, two were definitively identified as heat shock protein (Hsp90α) and stress‐70 protein. Hsp90α forms a heterocomplex with the glucocorticoid receptor (GR) and a significant decrease in GR following LTE₄ stimulation was confirmed. TGF‐β₁ downregulated 18 intracellular proteins, including lamin A/C, glyceraldehyde‐3‐phosphate dehydrogenase, protein DJ‐1, voltage‐dependent calcium channel gamma‐7 subunit, heterogeneous nuclear ribonucleoprotein A2/B1 and stress‐70 protein. Conclusions: The current findings suggest that by downregulating GR and Hsp90α, CysLT may interfere with the action of glucocorticoids. Overall, the results confirm the complex role of bronchial epithelium in aspects of airway inflammation and remodelling.     

Hepatoprotective action of prostaglandin A2 analogs under CCl4-induced liver injury in vitro

Aim: The cytoprotective effects of six novel synthetic prostaglandin A(2) analogs against carbon tetrachloride (CCl(4)) as a toxic agent were studied with isolated rat liver hepatocytes in vitro. Results: It was found that hepatocytes treatment with CCl(4) induced: (i) a significant increase of lactic dehydrogenase (LDH) release from cytoplasm; (ii) leakage of glutamate dehydrogenase (GDH) and acid phosphatase from mitochondria and lysosomes, respectively; (iii) 10-fold increase of trien conjugates formation; and (iv) a reduction of free SH-groups by 50%. Prostanoids U-26, U-9 and U-34 decreased cytotoxic index of CCl(4) on average by 1.5-2.0 times and were more effective than PGI(2), the well-known hepatoprotector of prostanoids type. The protective action of the prostanoids was not a cAMP- or Ca(2+)-dependent process. However, prostanoids U-26, U-9 and U-34 normalized intracellular content of SH-groups, reduced trien conjugates formation by 60-80% and strongly prevented enzyme leakage through cellular membranes. They were also able to inhibit CCl(4) effects via decreasing cytochrome P(450)2E1 activity. Conclusion: The results obtained demonstrate that prostanoids provide cytoprotective effects on liver hepatocytes through the prevention of lipid peroxidation of the plasma and the cellular membranes and maintenance of their barrier function.     

Inhibitory effect of prostaglandin E1 on intimal thickening following photochemically induced endothelial injury in the rat femoral artery

The inhibitory effect of prostaglandin E₁, which has an anti-platelet action and a vasodilating action via intracellular cyclic AMP elevation, was studied on intimal thickening in the rat femoral artery. A segment of the femoral artery was occluded by a platelet and fibrin-rich thrombus due to photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after endothelial injury, intimal thickening occurred at the irradiated site. Prostaglandin E₁ (0.3 μg/kg per min), administered as a continuous infusion 10 min before photochemical reaction significantly (P<0.05) prolonged the time to occlusion of the femoral artery. In a separate experiment, prostaglandin E₁ (0.3 μg/kg per min) administered as a continuous infusion for 7 days just after endothelial injury significantly (P<0.05) inhibited intimal thickening compared with a control group. In cultured rat-derived vascular smooth muscle cells, prostaglandin E₁ produced concentration-dependent inhibition of migration and proliferation, stimulated by platelet-derived growth factor. These results suggest that prostaglandin E₁ may be effective in preventing vascular restenosis after vascular surgery and angioplasty.     

吡格列酮对急性胰腺炎肝损伤的保护作用研究

目的:探讨吡格列酮对急性胰腺炎(AP)患者肝损伤的保护作用及其机制。方法:选取AP患者144例,使用数字表法随机分为观察组和对照组,每组72例。速率法检测血丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST),ELISA法检测外周血炎性因子:肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)、白介素-10(IL-10)。结果:治疗前2组血TNF-α、IL-6和IL-10水平以及ALT和AST等肝功能指标差异无统计学意义(均P0.05),治疗后观察组TNF-α和IL-6水平及ALT和AST均显著低于对照组(均P0.05),观察组血IL-10显著高于对照组(P0.05)。治疗前2组空腹血糖差异无统计学意义(P0.05),治疗后观察组的空腹血糖显著低于对照组(P0.05)。对照组不良反应发生率为5.6%(4/72),观察组不良反应发生率为6.9%(5/72),2组比较无统计学差异(P0.05)。结论:吡格列酮可以升高AP患者血IL-10表达,抑制炎症反应,发挥肝损伤保护作用,临床使用安全。     

The Effect of Prostaglandin E1 on Platelet Function in Vitro and in Vivo

S ummary Low concentrations of prostaglandin E₁ (PGE₁) inhibit ADP-induced aggregation in pig and rabbit citrated platelet-rich plasma and in suspensions of washed platelets. Higher concentrations also inhibit the initial change in shape induced by ADP and the release of platelet ATP, ADP and serotonin caused by stimuli such as collagen, thrombin, antigen-antibody complexes and gamma-globulin-coated polystyrene particles. PGE₁ is not taken up by platelets and its effects can be removed by resuspending platelets in fresh medium. Immediately following an intra-arterial injection, ADP-induced platelet aggregation is suppressed, but after 5 min the response returns to normal. PGE₁ inhibits haemostasis in rabbits when given as a continuous infusion. It is concluded that the effect of PGE₁ on haemostasis involves inhibition of the release of ADP from platelets exposed to collagen and thrombin, and inhibition of ADP-induced aggregation.     

Inhibitory effects of prostaglandin E_1 on activation of hepatic stellate cells in rabbits with schistosomiasis

BACKGROUND: Liver fibrosis is the result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. At the cellular and molecular levels, this progressive process is mainly characterized by activation of hepatic stellate cells (HSCs). Schistosoma japonica is one of the most prevalent causes of liver fibrosis in China. It is characterized by hepatocyte damage, inflammation, and chronic parasite egg-induced granuloma formation leading to fibrosis. This study aimed to investigate the inhibitory effects of prostaglandin E1 (PGE1) on activation of HSCs and the alteration of type Ⅰ and Ⅲ collagen in rabbits with schistosomiasis. The study may promote the clinical application of praziquantel and PGE1 as a combined therapy to reverse hepatic fibrosis caused by schistosomiasis. METHODS: Rabbits were percutaneously infected with cercaria of S. japonicum. Seven rabbits were subjected to intravenous injections of PGE1 (2.5 μg/kg daily) from days 60 to 120 after infection. The ultrastructural changes in activated HSCs were observed under transmission electron microscopy. The expression of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Fibril-forming collagens were detected by picrosirius staining. RESULTS: Activation of HSCs was a characteristic alteration in schistosome-induced hepatic fibrosis. The expression of contraction-related α-SMA and thecontent of collagens were increased. Exogenous PGE1 markedly inhibited the activation of HSCs and reduced the expression of α-SMA around the hepatic sinusoids (P<0.01). The contents of type Ⅰ and Ⅲ collagens were significantly attenuated. The ratio of staining area to the whole field (10×3.3) under a polarized light microscope in the untreated and treated groups was 37.25±9.71 vs. 13.38±4.24 (P<0.01) and 9.66±3.52 vs. 6.23±1.81 (P<0.05), respectively. CONCLUSIONS: Activation of HSCs may play a key role in the progress of schistosome-induced hepatic fibrosis. PGE1 effectively protects rabbit liver from fibrosis, at least in part by inhibiting the activation of HSCs.     

Therapeutic effects of caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis

AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）.
METHODS： Forty-two SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18）; SAP-ICE-i group （n = 18）. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion, in SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum 1L-1β was measured by EUSA. Intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated.
RESULTS： Serum IL-1β levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly （P 〈 0.01, vs HC）. in SAP- ICE-I group, those values were decreased significantly （P 〈 0.01, vs SAP-S）. intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group （P 〈 0.01, vs HC）. The expression of IL-lβ and IL-18 mRNA were decreased significantly in the SAP- ICE-I group （P 〈 0.01, vs SAP-S）, whereas Caspase-1 mRNA expression had no significant difference （P 〉 0.05）. The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly （P 〈 0.05 at 6 h, P 〈 0.01 at 12 h and 18 h, vs HC） and they were decreased significantly in the SAP-ICE-I group （P 〈 0.05, vs SAP-S）.Caspase-1 inhibitors ameliorated the severit     

小剂量前列腺素E1对严重充血性心力衰竭及内皮素的影响

为探讨小剂量前列腺素Ｅ１（ＰＧＥ１）对重度充血性心力衰竭及内皮素（ＥＴ）水平的影响,对２０例经传统治疗无效的心衰患者小剂量静滴ＰＧＥ１１周,观察治疗前后临床症状、血流动力学及ＥＴ变化。结果发现,临床总有效率为９５％。肺动脉压（ＰＡＰ）、肺毛细血管嵌楔压（ＰＣＷＰ）比治疗前明显下降（４．９３±０．５３对４．００±０．５３ｋＰｓ,Ｐ＜０．０１;３．４７±０．５３对２．５３±０．４０ｋＰａ,Ｐ＜０．０１）,体循环阻力指数（ＳＶＲＩ）下降（２０４．８±２１．３对１５０．６±１．３ｋＰａ·ｓ·Ｌ－１·ｍ－２,Ｐ＜０．０５）,心指数（ＣＩ）上升（２．２±０．１对２．８±０．２Ｌ·ｍｉｎ－１·ｍ－２,Ｐ＜０．０５）。内皮素明显降低（１５４．５６±４．４０对１１８．１３±２．２４ｎｇ／Ｌ,Ｐ＜０．０１）。提示ＰＧＥ１可降低ＥＴ水平并通过多种机制对心衰产生有益的作用。