全反式维甲酸对肾盂肾炎大鼠肾脏纤维化的影响

目的探讨全反式维甲酸（atRA）对肾盂。肾炎大鼠肾脏纤维化的影响。方法将40只大鼠随机分为正常对照组（A组）、假手术组（B组）、模型组（C组）和治疗组（D组）,每组10只。用致肾盂肾炎大肠杆菌制备大鼠肾盂肾炎模型。观察肾脏大体观改变和光境下HE、PAS染色肾组织纤维化的变化。结果A、B组大鼠尿细菌培养细菌数均〈1^5CFU／ml;C、D组大鼠尿细菌培养细菌数均〉10^5CFU／ml。A、B组大鼠肾脏的大体观和光镜下均正常,但D组较C组在肾脏大体观上肿胀程度减轻,光镜下纤维化程度减轻、肾盂肾盏扩张变形不明显。结论atRA能抑制肾盂肾炎大鼠肾脏炎症反应和纤维化的进展。     

The effect of prostacyclin on cerebral vasospasm an experimental study

Summary Prostacyclin (PGI₂), a strong vasodilator of cerebral vessels and potent inhibitor of platelet aggregation, was infused intravenously into seven cats after induction of prolonged vasospasm by hourly application of oxyhaemoglobin solution into the subarachnoid space round the basilar artery. PGI₂, at a concentration of 50 ng/kg/min, was effective in releasing the vasospasm in the seven cats. It did not produce significant hypotension. This report gives our results and the probable mechanism of action of PGI, in cerebral vasospasm.     

Influence of adenosine and prostacyclin on hypoxia-induced pulmonary hypertension in the anaesthetized pig

The effects of adenosine and prostacyclin (PGI2) infusions on hypoxia-induced pulmonary hypertension in the pulmonary and systemic circulatory systems of nine pigs were compared. The animals received the drugs in random order, and they were allowed to recover between each experimental sequence. Hypoxia was induced by reducing FiO2 to 0.12-0.13 so as to result in an arterial PO2 of approximately 6 kPa. Dose rates of adenosine or PGI2 during hypoxia were individualized in order to achieve a maximal reduction of 15% in the mean arterial blood pressure. Adenosine and PGI2 produced a fall in pulmonary vascular resistance of 36 +/- 4% (s.e.mean P less than 0.01) and 37 +/- 6% (P less than 0.01), respectively. The mean pulmonary artery pressure was reduced by 19 +/- 3% (P less than 0.01) during adenosine infusion and by 36 +/- 4% (P less than 0.01) during PGI2 infusion. The systemic haemodynamic responses to the two drugs were similar but adenosine produced a 7 +/- 2% (P less than 0.01) increase in cardiac output. Arterial PO2 during hypoxia and vasodilator treatment did not differ from the hypoxic situation without drug infusion. It is concluded that adenosine and PGI2 counteract hypoxia-induced increases in pulmonary vascular resistance similarly, but the reduction in pulmonary artery pressure was greater with PGI2 at infusion rates, causing minor systemic haemodynamic changes.     

Assessment of trans, trans-muconic acid in human seminal plasma

Trans, trans-muconic acid (tt-MA) is one of the most important metabolites of benzene, a pollutant ubiquitously distributed in ambient air and classified in 1982 as a group I carcinogen. For its sensitivity and specificity, tt-MA excreted in urine is considered a good biological marker of benzene exposure. In this study, seminal tt-MA levels in occupationally nonexposed subjects (n = 32) have been determined. The seminal fluid of normozoospermic subjects contained an average tt-MA concentration (170 +/- 100 ng ml-1) significantly lower than that of teratozoospermic (310 +/- 180 ng ml-1; P < 0.01), oligozoospermic (400 +/- 180 ng ml-1; P < 0.001), and oligoasthenozoospermic (430 +/- 230 ng ml-1; P < 0.01) subjects. A negative correlation existed between tt-MA levels and sperm concentration (r = - 0.62; P < 0.001), percentage of normal spermatozoa (r = - 0.41; P < 0.05), and percentage of vital spermatozoa (r = - 0.89; P < 0.001). Average tt-MA levels detected in seminal plasma were higher in smokers (350 +/- 160 ng ml-1) than in nonsmokers (280 +/- 210 ng ml-1). These results show that seminal plasma tt-MA content could be an important biological indicator for evaluating the negative effects of benzene on spermatogenesis.     

肝硬变门脉高压症病人门体分流术后血浆前列环素含量变化的研究

用放射免疫分析方法观察了１５例肝炎后肝硬变门静脉高压症病人血中前列环素含量的变化。结果显示，门体分流术后，门静脉及周围静脉血中前列环素含量分别下降了４９．６３％（Ｐ＜０．０１）和２１．６４％（Ｐ＜０．０５）。门静脉血中前列环素含量的下降与门静脉压的下降呈正相关（ｒ＝０．７４，Ｐ＜０．０５）。表明肝硬变病人体内前列环素含量的增加主要是由于内脏血管内皮细胞合成增加所致，前列环素对门静脉高压症的形成以及维持其高压状态持续存在起一定作用。     

An outcome study of severe traumatic head injury using the "Lund therapy" with low-dose prostacyclin

Background: There are two independent head injury outcome studies using the “Lund concept”, and both showed a mortality rate of about 10%, and a favourable outcome (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at controlling intracranial pressure, and improving microcirculation around contusions. Intracranial pressure is controlled by maintaining a normal colloid osmotic pressure and reducing the hydrostatic capillary pressure. Microcirculation is improved by ensuring strict normovolaemia and reducing sympathetic discharge. The endogenous substance prostacyclin with its antiaggregatory/antiadhesive effects may further improve microcirculation, which finds support from a microdialysis‐based clinical study and an experimental brain trauma study. The present clinical outcome study aims at evaluating whether the previously obtained good outcome with the Lund therapy can be reproduced, and whether the addition of prostacyclin has any adverse side‐effects. Methods: All 31 consecutive patients with severe head injury, Glasgow coma scale (GCS) ≤8, admitted to the University Hospital of Umeå during 1998 were included. The Lund therapy including prostacyclin infusion for the first three days at a dose of 0.5 ng kg^?1 min^?1. Outcome was evaluated according to the GOS >10 months after the injury. Results: One patient died, another suffered vegetative state and 7 severe disability. Of the 22 patients with favourable outcome, 19 showed good recovery and 3 moderate disability. No adverse side‐effects of prostacyclin were observed. Conclusion: The outcome results from previous studies using the Lund therapy were reproduced, and no adverse side‐effects of low‐dose prostacyclin were observed.     

全反式维甲酸在小肠缺血再灌注中的炎症抑制效应及机制

目的探讨全反式维甲酸（ATRA）对大鼠小肠缺血再灌注的炎症抑制作用和机制。方法24只雄性SD大鼠,每组8只,随机分为假手术组、阻断组和ATRA组。ATRA组术前以ATRA15mg·kg-1·d。灌胃,阻断组以等体积溶媒二甲基亚砜（DMSO）灌胃,共5d。术中阻断肠系膜上动脉60rain后再灌注120min,收集各组大鼠末端回肠和血清。光学显微镜下观察回肠病理学改变、行肠黏膜Chiu氏评分;比色法测定血清二胺氧化酶（DAO）含量和回肠组织髓过氧化物酶（MPO）活性;ELISA法测定回肠组织肿瘤坏死因子仅（TNF-a）及白介素1B（IL-1β）水平;Westernblot检测回肠组织中胞核NF—KBp65蛋白和胞质NF—KB抑制蛋白d（IKBd）的表达量。结果与阻断组相比,ATRA组回肠黏膜病理损伤减轻,Chiu氏评分下降[（2．54±0．69）US．（3．86±0．83）,P〈0．05],血清DAO含量减少[（18．09±4．21）U／LUS．（24．56±4．92）U／L,P〈0．05],组织TNF-d[（61．37±18．66）pg／g135．（97．21±24．67）Pg／g]、IL—1β水平[（115．24±30．82）pg／gcs．（219．83±54．31）pg／g]和MPO活性[（4．62±1．18）U／gUS．（7．16±1．50）U／g]降低,均P〈0．05;胞核NF—KBp65蛋白表达下调[（3．71±0．83）vs．（6．59±1．05）,P〈0．051,胞质IKB仪蛋白含量增加[（0．56±0．12）vs．（0．26±0．05）,P〈0．05]。结论ATRA预处理可以抑制NF—KB的激活,减轻组织的过度炎症反应,对大鼠小肠缺血再灌注损伤具有保护作用。     

Clinical studies on the vasodilating and anti-platelet effects of OP-41483, a prostacyclin derivative

The vasodilating and anti-platelet actions of OP-41483 was studied to determine the effective dose of this drug for the treatment of ischemic lower limbs. The compound was given to 11 patients intravenously at rates of 2.5, 5.0 and 10.0 ng/kg/min. Infusion at a rate of 10 ng/kg/min increased the mean flow rate of the tibial arteries from 3.15±1.77 ml/min before the infusion, to 7.89±2.51 ml/min (p<0.001) and to 6.38±3.19 ml/min (p<0.001), at the time of, and 60 minutes after the cessation of the infusion, respectively. The peripheral flow resistance of the tibial arteries was reduced from 2.1±1.12×10⁵ dyne·sec/cm⁵ before the infusion to 0.9 ±0.33×10⁵ dyne·sec/cm⁵ (p<0.001) and to 1.2±0.78×10⁵ dyne·sec/cm⁵ (p<0.05), at the time of, and 60 minutes after the cessation of the infusion. ADP-induced platelet aggregation was reduced from 73.3±17.6% before the infusion to 50.7±24.5% (p<0.01) and to 64.0±23.5% (p<0.05), at the time of, and 60 minutes after the cessation of the infusion, respectively. Collageninduced platelet aggregation was also reduced from 71.4±24.0% to 66.6±21.5% before and after the infusion (p<0.05).     

Effects of autologous mesothelial cell seeding on prostacyclin production within Dacron arterial prostheses

Canine abdominal aortas have been replaced with Dacron arterial prostheses to assess the effects of mesothelial cell seeding on graft prostacyclin and thromboxane A2 release. At both 2 weeks and 6 weeks after surgery, three seeded and two unseeded control grafts were examined for prostacyclin release. In addition, thromboxane release was assessed in one seeded and one unseeded graft. Sections of aorta and graft were removed and incubated in PBS containing either 10 microM calcium ionophore A23187 or 20 microM arachidonic acid. The incubation mixture was sub-sampled at 5 min intervals over a 20 min period to assess the progressive release of prostacyclin and thromboxane A2 using a radioimmunoassay for 6-keto-prostaglandin F1 alpha and thromboxane B2 respectively. In seeded grafts, 6-keto-prostaglandin F1 alpha release averaged 15 per cent compared with aorta at 2 weeks and 45 per cent compared with aorta at 6 weeks. By contrast, release from unseeded grafts was undetectable at 2 weeks; however, by 6 weeks there was some release amounting to 15 per cent compared with aorta. There was a statistically significant increase in the release of 6-keto-prostaglandin F1 alpha from mesothelial cell seeded grafts at 6 weeks compared with unseeded grafts (P less than 0.01). Thromboxane release from the graft sections was variable and unrelated to whether the grafts had been seeded or not. These preliminary results, showing that grafts seeded with autologous peritoneal mesothelial cells release more prostacyclin than unseeded grafts, further highlight the role of the mesothelial cell as an alternative to the endothelial cell for improving the patency of arterial Dacron prostheses in the early postoperative days.     

Suppression of pseudointimal hyperplasia by a novel prostacyclin analogue: Beraprost

The aim of this study was to evaluate the effect of a novel prostaglandin I₂ analogue, beraprost (BPT), on the pseudointimal hyperplasia (PIH) of polytetrafluoroethylene (PTFE) prostheses. A total of 12 rabbits were equally divided into three groups. The control group was given a placebo daily, group 1 was given BPT orally 2 mg/kg per day, and group 2 was given BPT orally 4 mg/kg b.i.d. Exactly 1 cm of the inferior vena cava was resected and replaced by a 3-cm PTFE tube graft. All the grafts were patent when harvested 4 weeks after implantation, but the lumens were narrowed to various extents by PIH. PIH, determined by the dry weight of the intraluminal tissue deposit, was significantly (P<0.01) suppressed in groups 1 and 2 compared with the control group. High-magnification light microscopy with various staining methods revealed the PIH to be composed mainly of smooth muscle cells (SMCs) and collagen fibrils in all three groups. Transmission electron microscopy revealed that the majority of SMCs in groups 1 and 2 were contractile in form, in contrast with the synthetic form seen in the control group. In conclusion, BPT attenuated the PIH of PTFE grafts by inhibiting the phenotype change in the SMCs.     

全反式维甲酸联合干扰素-β对人骨肉瘤细胞株MG-63的生长抑制作用

目的 观察全反式维甲酸(ARTA)联合干扰素(IFN)-β对人骨肉瘤细胞株MG-63的生长抑制试验以及对干扰素/维甲酸联合应用诱导凋亡的相关基因19( GRIM-19)和原癌基因信号转导与转录激活因子-3( STAT3)的表达的影响.方法 噻唑蓝(MTT)比色法检测不同药物浓度的ATRA/IFN-β,单用或联合应用对MG-63的增殖抑制率；流式细胞仪AnnexinV-FITC/PI法检测MG-63的凋亡；逆转录-聚合酶链反应(RT-PCR)检测MG-63中STAT3与GRIM-19基因的扩增情况；Western blot检测MG-63中STAT3与GRIM-19蛋白的表达.结果 ARTA和IFN-β单用或联合应用均可抑制MG-63的增殖,呈浓度依赖性并与作用时间有关；联合应用抑制作用明显增强,与其他组比较差异有统计学意义(P＜0.05).ARTA、IFN-β单独作用,可诱导MG-63凋亡；联合应用时,诱导凋亡作用显著增强.ARTA联合IFN-β作用,GRIM-19 mRNA的表达明显增强(1.620±0.095),GRIM-19蛋白明显升高(1.850±0.060),与其他组比较差异有统计学意义(P＜0.01).STAT3 mRNA的表达明显降低(0.120 ±0.032),STAT3蛋白明显降低(0.540±0.075),与其他组比较差异有统计学意义(P＜0.01).结论 ARTA/IFN-β作用,可明显抑制MG-63的增殖并诱导其凋亡,其机制可能是诱导GRIM-19高表达,特异性结合于STAT3的转录活性区域,使原癌基因STAT3的表达降低.     

Possible role of arachidonic acid in the regulation of lactate production in rat Sertoli cells

The aim of the study was to determine whether arachidonic acid (AA) is involved in the regulation of Sertoli cell lactate production and if this fatty acid participates in follicle-stimulating hormone (FSH) regulation of Sertoli cell function. In a first set of experiments the effect of AA and porcine pancreas phospholipase A2 (PLA2) on lactate production, glucose uptake, lactate dehydrogenase (LDH) activity and LDH A mRNA levels in Sertoli cell cultures obtained from 20-day-old rats was evaluated. In a second set of experiments the effect of two PLA2 inhibitors--quinacrine (Q) and AACOCF3--on FSH stimulation of the above-mentioned parameters of Sertoli cell function was investigated. Treatment with PLA2 and AA increased Sertoli cell lactate production. The observed action of exogenously added PLA2 involved its catalytic properties responsible for AA release. PLA2 and AA treatments also stimulated Sertoli cell glucose uptake, LDH activity and LDH A mRNA levels. In order to determine whether AA participates in FSH regulation of Sertoli cell lactate production cells were incubated with FSH in the absence or presence of the PLA2 inhibitors Q and AACOCF3. Both drugs partially inhibited the ability of FSH to stimulate lactate production, glucose uptake and LDH activity. The present investigation suggests that AA is involved in the regulation of lactate production, glucose transport, LDH activity and LDH A mRNA levels. In addition, these results suggest that cytosolic PLA2 and AA may participate in FSH-regulation of Sertoli cell energetic metabolism.     

The effects of activated protein C and prostacyclin on arterial oxygenation and protein leakage in the lung and the gut under endotoxaemia in the rat

Background: Based on the anti-adhesive/anti-aggregatory and permeability-reducing properties of activated protein C (APC) and prostacyclin (PGI₂), we analysed and compared these substances regarding their efficacy in counteracting transcapillary leakage of albumin in the lung and the gut, and in improving arterial oxygenation under a condition of inflammation.
Methods: The randomized and blinded study was performed on 31 adult male Sprague-Dawley rats. Inflammation was induced by continuous infusion of Escherichia coli endotoxin (lipopolysaccharide, LPS). Six hours after the start of the LPS infusion (240,000 U/kg/h), a simultaneous infusion of saline (control group) or 8 μg/kg/min of human recombinant APC or 2 ng/kg/min of PGI₂ was started and continued for 24 h ( n =8 per group). The study also included a sham group. Transcapillary leakage of albumin was measured from the ratio between tissue radioactivity [counts per minute (cpm)/g tissue] and actual amount of radioactivity given (cpm/g body weight of ¹²⁵I-albumin). Oxygenation was assessed from arterial and central venous blood samples.
Results: LPS induced albumin leakage in the gut and the lung, and impaired blood oxygenation. In the lung, the leakage was lower in the PGI₂ group than in the APC and the control groups ( P <0.05). In the gut, it was lower in the APC and the PGI₂ groups than in the control group ( P <0.05). Oxygenation was better in the APC and PGI₂ groups than in the control group.
Conclusion: Our data suggest that both APC and low-dose PGI₂ are beneficial in LPS-induced inflammation in the rat, by reducing albumin leakage and improving blood oxygenation.     

全反式维甲酸对结肠癌不同增殖能力细胞株iNOS表达的影响

目的探讨全反式维甲酸 (alltransretinoicacid ,ATRA)对结肠癌不同增殖能力细胞株i NOS表达的影响。方法采用MTT方法确定结肠癌细胞株CW 2和LS174T的生长增殖状况 ,用RT PCR和Northernblot方法检测结肠癌中iNOSmRNA的表达量 ;用Westernblot确定iNOS蛋白的表达。结果结肠癌细胞株LS174T的生长增殖比CW 2快 ;CW 2细胞株和LS174T细胞株均有iNOS的表达 ;在CW 2中有较高的iNOS表达 ;ATRA对结肠癌CW 2和LS174T细胞株iNOSmRNA和蛋白的表达量无明显影响。结论iNOS对结肠癌细胞株增殖有双重作用 ,即在低增殖结肠癌CW 2呈高表达 ;在高增殖结肠癌LS174T呈低表达。ATRA可以抑制结肠癌细胞株的生长 ,但ATRA对iNOSmRNA和蛋白的表达量无明显影响。     

Effects of prostacyclin infusion on renal function during cardiopulmonary bypass

Infusion of prostacyclin inhibits platelet activation during cardiopulmonary bypass (CPB) but also results in systemic arterial hypotension. Therefore, the effects of CPB and prostacyclin on renal function were studied in 36 male patients undergoing aortocoronary bypass. Nineteen patients (Group 1) received prostacyclin, 50 ng per kilogram of body weight per minute, during CPB, and 17 patients (Group 2) served as controls. There was pronounced hypotension in Group 1 only. Urine production during CPB averaged 88 +/- 140 ml and 2,306 +/- 1,112 ml in Groups 1 and 2, respectively. No patient had renal failure. Glomerular filtration rate (GFR), as measured by clearance of chromium 51-labeled ethylenediaminetetraacetic acid, was increased in Group 1 from 86 +/- 14 to 99 +/- 22 ml/1.73 m2/min (p less than 0.05) the day after operation, but remained unchanged in Group 2 (81 +/- 15 to 82 +/- 21 ml/1.73 m2/min). The increased GFR in Group 1 can be regarded as an expected adaptation to the change in body fluids after CPB. Therefore, the unchanged GFR in Group 2 must be regarded as caused by insufficient adaptation or impaired renal function. Proximal tubular function was evaluated by determination of beta 2-microglobulin in urine. In both groups, urinary beta 2-microglobulin and the ratio of urinary beta 2-microglobulin to urinary creatinine were increased the day after operation. The hypotension in Group 1 did not exacerbate the damage to tubular function.     

高渗氯化钠溶液对前列环素和内皮素的影响

比较３０例硬膜外阻滞择期手大患者，输入７．５％ＨＳ和５％ＧＳ后血浆ＰＧＩ２、ＥＴ及血流动力学的变化。输入ＨＳ后ＰＧＩ２明显升高，ＥＴ显著降低，伴主动脉顺应性快速增加。输入ＧＳ后１０分钟ＰＧＩ２和ＥＴ均无明显变化，６０分钟时ＰＧＩ２轻度增加，ＥＴ亦有上升，但较离散；ＴＰＲ持续增加，ＣＯ和ＳＶ短暂降低，血压明显下降。本研究提示ＰＧＩ２和ＥＴ在ＨＳ降低外周血管阻力、改善血流动力学过程中可能起着重要的介导作用。     

Effects of prostacyclin injections and infusions on canine femoral hemodynamics

The use of prostacyclin (PGI₂) infusions has been recommended in the management of patients with severe distal arteriopathy, who are not candidates for conventional bypass procedures. Further clarification regarding the route of administration and the optimal dose of this potent vasodilator, however, is needed before controlled clinical trials are initiated. We measured bilateral femoral arterial blood flow electromagnetically in seven anesthetized adult mongrel dogs. Systemic arterial pressure and cardiac output were also measured. Central venous and femoral arterial injections of PGI₂ were administered in five doses ranging from 10⁻⁴ to 10⁰ μg · kg⁻¹ to study the dose response. PGI₂ was also infused intravenously and intra-arterially for 20 minutes at a dose of 10⁻¹ μg · kg⁻¹ · min⁻¹. Femoral arterial injections of PGI₂ in doses from 10⁻⁴ through 10⁰ μg · kg⁻¹ caused significant (p < 0.05) and dose-dependent increases in ipsilateral femoral arterial blood flow. Intravenous injections of PGI₂ caused no significant changes in the dose range from 10⁻⁴ to 10⁻² μg · kg⁻¹ but resulted in a significant (p < 0.05) reduction in femoral arterial flow and systemic arterial pressure at doses of 10⁻¹ and 10⁰ μg · kg⁻¹. The femoral arterial infusion of PGI₂ produced a significant and sustained increase in femoral arterial flow that was not observed during the intravenous infusion. Arterial pressure was unchanged with intra-arterial PGI₂ but was significantly reduced during the intravenous infusion. The beneficial hemodynamic effects of intra-arterial PGI₂ suggest that further clinical trials should employ this route of administration. On the basis of these data, intravenous administration of the drug will have limited clinical application.