前列环素及Dazmegrel对急性出血坏死性胰腺炎大鼠肺损伤的防治作用

前列环素及Ｄａｚｍｅｇｒｅｌ对急性出血坏死性胰腺炎大鼠肺损伤的防治作用王兴鹏徐家裕袁耀宗应用血栓素（ＴＸＡ＿２）合成酶抑制剂Ｄａｚｍｅｇｒｅｌ（Ｄａ）及外源性ＰＧＩ＿２调节ＴＸＡ＿２、ＰＧＩ＿２平衡，观察其对大鼠急性出血坏死性胰腺炎（ＡＨＮＰ）并发肺...     

一氧化氮与门脉高压性肠病关系的实验研究

目的探讨ＮＯ在门脉高压性肠病发病机理中的作用。方法制作大鼠四氯化碳门脉高压模型。第１２周末，在冰冻切片上进行结肠ＮＡＤＰＨ黄递酶组织化学染色；应用化学发光法测定ＮＯＳ活性；ＲＴ－ＰＣＲ反应测定ＮＯＳｍＲＮＡ表达量。结果（１）ＮＡＤＰＨ黄递酶组化染色：模型组大鼠结肠粘膜下小血管内皮细胞和神经纤维的ＮＯＳ染色强度显著高于正常对照组。而表层上皮细胞ＮＯＳ染色减弱。（２）化学发光法测定ＮＯＳ活性：模型组大鼠结肠粘膜ＮＯＳ活性较正常对照组显著增加，其中ｉＮＯＳ活性增加更为明显。（３）ＲＴ－ＰＣＲ：模型组大鼠结肠粘膜ＮＯ－ＳｍＲＮＡ表达量较正常对照组显著增加。结论ＮＯ可能由于其扩张血管的特性，而参与门脉高压性肠病血管病变的发病过程，并与门脉高压性肠病粘膜病变、可能存在的运动功能异常亦有一定的关系。     

电针足三里穴对应激性胃溃疡大鼠一氧化氮和儿茶酚胺的影响

本文对电针足三里穴抗“束缚－冷冻”应激性胃溃疡大鼠一氧化氮（ＮＯ）、多巴胺（ＤＡ）和去甲肾上腺素（ＮＥ）的含量进行了分析，结果如下：①应激性胃溃疡大鼠血清ＮＯ含量比对照组非常显著下降， Ｐ＜０． ０１，胃窦粘膜ＤＡ含量显著下降， Ｐ＜０． ０５，胃体粘膜ＤＡ呈增高趋势；②电针足三里穴引起应激性胃溃疡大鼠ＮＯ水平回回升，与应激组相比， Ｐ＜０．０１。电针引起胃窦和胃体粘膜ＤＡ、ＮＥ含量改变，有双向调节作用。即原降低者上升、原升高者下降，分别与应激组相比，均为Ｐ＜０． ０１。提示电针对胃粘膜的保护作用是通过对ＤＡ和 ＮＥ的双向调节，发挥了ＤＡ的调控作用，影响ＮＥ的水平，通过ＮＯ的舒血管作用，调节血流量，增强粘膜防御能力而实现的。     

电针足三里穴对应激性胃溃疡大鼠一氧化氮和儿茶酚胺的影响

目的研究电针足三里穴对束缚———冷冻应激性胃溃疡大鼠一氧化氮、多巴胺和去甲肾上腺素的影响．方法应用生物化学方法分析胃窦、胃体粘膜和血液中ＮＯ、ＤＡ和ＮＥ含量在电针前后的变化，随机分为四组：应激性胃溃疡组、应激后电针组、先电针后应激组和对照组进行观察．结果①应激性胃溃疡大鼠血清ＮＯ含量（ｘ±ｓ，５７８±１４９μｍｏｌ／Ｌ）比对照组（１３３０±２７５）非常显著下降，Ｐ＜００１；胃窦粘膜ＤＡ含量显著下降（３３１±０６７ｖｓ６７８±４６５），Ｐ＜００５，胃体粘膜ＤＡ呈增高趋势．②电针足三里穴引起应激性胃溃疡大鼠ＮＯ水平回升（７９１±１１１），与应激组相比，Ｐ＜００１．电针引起胃窦和胃体粘膜ＤＡ及ＮＥ含量改变，有双向调节作用，即原降低者上升、原升高者下降，分别与应激组相比，均为Ｐ＜００１．结论电针对胃粘膜具有保护作用，它是通过针刺对ＤＡ和ＮＥ的双向调节，发挥了ＤＡ的调控作用，影响ＮＥ的水平，通过ＮＯ参与的舒血管作用，调节血流量、增强粘膜防御能力而实现的．     

射频消蚀术前后血清心肌酶变化的研究

对３３例患者射频消蚀术（简称ＲＦＣＡ）前后的血清心肌酶（ＣＫ、ＣＫ－ＭＢ．ＡＳＴ、ＬＤＨ、ＬＤＨ１）进行动态观察。结果表明：ＲＦＣＡ后血清心肌酶活性均有不同程度的升高（Ｐ＜０．０１）；ＣＫ及ＣＫ－ＭＢ于术后６小时达到峰值，２４小时恢复至正常水平，ＡＳＴ于术后１２小时达峰值、时达峰值，７２小时恢复正常，ＬＤＨ及ＬＤＨ，的达峰及恢复时间分别为２４小时和１２０小时；多元线性相关分析显示心肌酶活性的升高程度与消蚀靶点个数呈高度正相关（ｒ＝０．８１３６，Ｐ＜０．００１）．揭示ＲＦＣＡ对心肌组织有不同程度的损伤，影响心肌损伤范围的主要因素是消蚀靶点的多少。因此，在ＲＦＣＡ中，应力求标测定位准确，尽量减少试探性放电，以最大限度地减少心肌损伤。     

血小板活化因子受体拮抗剂BN50739脑保护作用的实验研究

目的观察血小板活化因子（ＰＡＦ）特异性受体拮抗剂ＢＮ５０７３９对实验性脑缺血的脑保护作用。方法采用光化学诱导鼠大脑中动脉闭塞及再通模型，观察ＢＮ５０７３９对脑缺血大鼠局部脑组织血流量、脑含水量、脑组织抗氧化剂活性、超氧化物歧化酶（ＳＯＤ）活性以及脑组织超微结构的改变。结果ＢＮ５０７３９治疗组大鼠局部脑组织血流量较单纯缺血组增加３０％以上（Ｐ＜０．０１），同时ＢＮ５０７９３明显改善了脑缺血再灌注期脑组织抗氧化剂活性及ＳＯＤ活性，减轻缺血脑组织水肿及神经元的坏死（均为Ｐ＜０．０５）。结论血小板活化因子是脑缺血病理损害过程中的一个重要活性介质，其受体拮抗剂ＢＮ５０７３９对实验性脑缺血组织有明确的脑保护作用     

粒细胞弹力蛋白酶是重症胰腺炎并发急性肺组织损伤的关键因素

目的应用大鼠牛磺胆酸钠重症胰腺炎模型探讨粒细胞弹力蛋白酶（ＰＭＮＥ）和磷脂酶Ａ２（ＰＬＡ２）在重症胰腺炎（ＳＡＰ）并发急性肺组织损伤中的作用。方法测定发病后３、６、１２小时肺组织内ＲＭＮＥ和ＰＬＡ２的活性变化，同时观察肺组织的光镜、电镜病理改变。结果实验组ＰＭＮＥ的活性皆高于对照组（Ｐ＜０，０５），３小时活性最低。６小时最高，１２小时的酶活性降低。但仍高于３小时。ＰＭＮＥ的活性与肺内ＰＭＮ浸润数目呈正相关（ｒ＝０．９６４）。３小时和６小时的ＰＬＡ２活性较对照组有显著升高（Ｐ＜０．０５），但１２小时的活性低于对照组。ＰＬＡ２的活性与肺内ＰＭＮ浸润数目无相关性。肺组织的病理改变随时间而加重，可见粒细胞浸润、激活和肺Ⅱ型上皮细胞损伤和间质水肿。结论粒细胞肺内浸润激活和其释放的ＰＭＮＥ是重症胰腺炎并发肺组织损伤的关键因素，ＰＬＡ２和肺损伤无明显关系。     

一氧化氮供体对离体大鼠心脏心肌缺血再灌注损伤不同时间的作用

目的：探讨在心肌缺血再灌注过程的不同时期补充一氧化氮（ＮＯ）对心肌损伤的影响。方法：以离体灌流大鼠心脏作为缺血（３０分钟）再灌注（６０分钟）模型。４８只心脏分为４组：Ａ组（ｎ＝１１）仅于再灌注期初２０分钟内给予硝酸甘油（ＮＯ供体）；Ｂ组（ｎ＝１２）于低流量缺血期及再灌注期初２０分钟内均给予硝酸甘油；Ｃ组（ｎ＝１４）为缺血再灌注对照组；Ｄ组（ｎ＝１１）仅于低流量缺血期给予硝酸甘油。测定心功能及肌酸激酶漏出量，同时测定心脏ＮＯ释放量。结果：Ｂ组及Ｄ组缺血后心功能的恢复明显低于Ｃ组和（或）Ａ组。Ｂ组缺血后冠状动脉流量的恢复显著低于Ａ组。Ｂ组及Ｄ组缺血再灌注期肌酸激酶漏出量明显大于Ｃ组及Ａ组。结论：Ｂ组对心肌组织的损伤最重；Ｄ组可损伤心肌细胞；Ａ组对心肌组织无损害。     

急性坏死性胰腺炎肠粘膜屏障功能障碍及生长激素的作用

目的 探讨急性坏死性胰腺炎（ＡＮＰ）肠粘膜屏障形态和功能的变化及生长激素（ＧＨ）的作用。方法 采用胰胆管内逆行注射５％牛磺胆酸钠溶液诱导大鼠ＡＮＰ。实验分３组：假手术组、ＡＮＰ＋生理盐水（ＮＳ）组、及ＡＮＰ＋ＧＨ组。术后２４h取末端回肠,观察病理形态变化;应用＾１２５Ⅰ－白蛋白测定肠壁通透性;ＲＴ－ＰＣＲ检测胰岛素样生长因子（ＩＧＦ－１）mＲＮＡ表达。结果 ＡＮＰ大鼠肠粘膜间质充血水肿,炎症细胞浸     

活动期,愈合期及瘢痕期球溃疡患者胃酸及胃窦粘膜胃肠…

作者比较了活动期、愈合期及瘢痕期球溃疡患者和非溃疡对照，患者的基础胃酸分泌量，高峰胃酸分泌量及胃窦粘膜内胃泌素，生长抑素，血管活性肠肽，Ｐ物质的含量，发现各球溃疡患者ＰＡＯ均明显高于ＮＵ组；ＡＤＵ组胃窦粘膜Ｇａｓ及ＳＰ含量比ＮＵ组明显增加；ＳＤＵ组胃窦粘膜内ＳＳ较ＮＵ组明显增加。本文结果说明壁细胞泌酸能力增加是ＤＵ发病的重要病理生理基础，基础胃酸高分泌状态是ＤＵ患者溃疡活动的重要条件，ＡＤＵ患者Ｂ     

血小板活化因子在急性胰腺炎大鼠并发肾损伤中病理生理作用

目的:本文旨在观察血小板活化因子在急性出血坏死性胰腺炎(AHNP)大鼠肾损伤发生中作用。方法:159只SD大鼠随机分三组:假手术组、AHNP非治疗组和AHNP BN(52021)治疗祖。采用胰管内注入5％牛磺胆酸钠溶液诱导大鼠AHNP,应用~(86)Rb组织摄取法测定肾脏相对血流量及组织灌注量,并测定血小板聚集率(PAgR)。结果:与非治疗组相比较,BN(52021)治疗组肾脏相对血流量、组织灌注量显著提高;PAgR下降;肾脏病理损害减轻。结论:血小板活化因子参与了急性出血坏死性胰腺炎大鼠肾损害的发生。     

血小板活化因子受体拮抗剂干扰实验性肾炎的疗效观察及机理探讨

实验大鼠均制成加速型抗肾小球基膜（GBM）肾炎模型，分为三组：模型组、血小板活化因子（PAF）受体拮抗剂BN－52021组和血栓素A2（TXA2）合成酶抑制剂UK－38485组，结果BN－52021组大鼠各期尿蛋白量较模型组显著减少（P＜0．01），第21天时血清肌酐、肾皮质内TXB2含量较模型组显著降低（P＜0．01）；光镜和电镜下肾组织病理改变明显较模型组为轻；UK-8485组尿蛋白量也倾向于较模型组减少，担无统计学意义．第21天时血清肌酐、肾皮质内TXB2含量也较模型组显著降低（P＜0．01）．本实验表明，PAF受体拮抗剂干扰该大鼠肾炎有效，其有效机理可能部分是通过减少肾皮质TXA2合成而介导的。     

Interactions between platelet-activating factor and prostanoids during mesenteric ischemia-reperfusion-induced shock in the anesthetized dog.

The effects of platelet-activating factor (PAF) on prostanoid release during mesenteric ischemia-reperfusion-induced shock were investigated in anesthesized dogs 1) by measuring plasma levels of prostaglandin (PG)F2 alpha, 6-keto-PGF1 alpha and thromboxane (TX)B2 in the superior mesenteric vein during reperfusion following 2 hr occlusion of the superior mesenteric artery; 2) by monitoring the effects of BN 52021, a specific PAF receptor antagonist and indomethacin on hemodynamic parameters and prostanoid levels; and 3) by studying circulatory responses to PAF and PGF2 alpha injected into the superior mesenteric vein in the presence of BN 52021 or indomethacin. Restoration of the blood flow following 2 hr ischemia resulted in an immediate dramatic decrease in mean arterial blood pressure, with a concomitant increase in mean portal venous pressure, hematocrit values, and plasma prostanoid levels. Pretreatment of the animals either with BN 52021 (4 mg.kg-1) or indomethacin (2 mg.kg-1 plus 3 mg.kg-1hr-1) prevented the circulatory collapse and the increase in prostanoid levels during reperfusion. Administration of exogenous PAF (0.1 micrograms.kg-1) or PGF2 alpha (10 micrograms.kg-1) into the superior mesenteric vein evoked hypotension similar to that observed during reperfusion. Pretreatment of the animals with BN 52021 completely prevented the effects of PAF but failed to modify the responses to PGF2 alpha. Indomethacin at a dose that inhibited prostanoid formation was highly effective to attenuate the hypotensive response to exogenous PAF. These data suggest that prostanoid formation may be secondary to PAF release in circulatory collapse evoked by intestinal ischemia-reperfusion and give further support to the notion of the importance of PAF prostanoid interaction during ischemia-reperfusion-induced shock.     

Mechanism and dose-effect of Ginkgolide B on severe acute pancreatitis of rats

AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoperation group(SO),SAP model group(SAP),dimethyl sulfoxide(DMSO) contrast group(DMSO),and groups treated with 2.5 mg/kg BN52021(BN1),5 mg/kg BN52021(BN2),10 mg/kg BN52021(BN3),and 20 μg/kg Sandostatin(SS).The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely...     

Evidence for a role of platelet activating factor in the pathogenesis of irreversible but not reversible myocardial injury after reperfusion in dogs

The role of platelet activating factor (PAF) in myocardial injury after either brief (15 minutes, stunned myocardium) or prolonged (90 minutes, infarcted myocardium) coronary artery occlusion and 3 hours of reperfusion of the left anterior descending coronary artery was investigated in barbital-anesthetized dogs. Regional myocardial blood flow was measured by radioactive microspheres, regional segment shortening by sonomicrometry, and infarct size by the triphenyltetrazolium chloride stain. Infarct size expressed as a percentage of the area at risk was significantly reduced by the intravenous administration of two structurally unrelated PAF antagonists, BN 52021 (10 mg/kg and 1 mg/kg/hr) and CV-3988 (3 mg/kg and 0.3 mg/kg/hr). Infarct size was 38% +/- 5% in the saline (control) group, (n = 7), 22% +/- 5% in the BN 52021 group (n = 7), and 19% +/- 5% in the CV-3988 group (n = 8). However, the intravenous administration of BN 52021 (5 and 10 mg/kg) and CV-3988 (5 mg/kg) had no effect on functional recovery (regional segment shortening) in the stunned myocardium after brief occlusion and reperfusion. Regional myocardial blood flow, hemodynamic data, and the incidence of cardiac arrhythmias were not significantly affected by PAF antagonists in both series of experiments at any time. These data suggest that PAF may play an important role in the pathogenesis of an evolving myocardial infarction that follows a prolonged coronary artery occlusion and reperfusion. Furthermore, PAF antagonists may have a beneficial role in reduction of the injury produced during an acute infarction. Finally, these data indicate that PAF does not appear to be an important mediator of myocardial stunning.     

银杏苦内酯B对急性坏死性胰腺炎大鼠肺组织PAF—R表达的影响

目的观测银杏苦内酯B（BN52021）干预前后ANP大鼠肺组织血小板活化因子受体（PAF-R）mRNA和蛋白质表达的变化,探讨其作用机制。方法180只大鼠随机分为对照组（NC组）、ANP组和BN52021治疗组（BN组）,每组再分为制模后1h、2h、3h、6h、12h、24h6个亚组。逆行胰胆管内注射牛磺胆酸钠诱导ANP。BN组于制模后15min股静脉注入BN52021（0.5mg/100g体重）。各时间点取血检测血清淀粉酶,取胰腺和肺组织行病理学检查,采用RT-PCR和Western blot检测肺组织PAF-R mRNA和蛋白质表达。结果ANP组和BN组各时点血清淀粉酶均高于NC组（P〈0.05）,BN组1h、2h、3h、6h、24h时点均低于ANP组（P〈0.05）。ANP组和BN组胰腺和肺的病理分值均高于NC组,BN组在3h、6h、12h显著低于ANP组（P〈0.05）。ANP组和BN组PAF-R mRNA和蛋白质水平分别在3h和1h显著高于NC组,BN组与ANP组相比无显著差异。结论PAF-R在ANP早期急性肺损伤中起重要作用,BN52021对其表达无显著影响。     

The effect of platelet activating factor antagonist (BN 52021) on acute experimental pancreatitis with reference to multiorgan oxidative stress

Summary Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were treated with platelet-activating factor receptor (PAF) antagonist—BN 52021 (5 mg/kg) and sacrificed at 1 and 3 h after induction of acute pancreatitis. Malondialdehyde and sulfhydryl groups concentration were measured in pancreatic, lung, and liver tissue as a parameters of oxidant-antioxidant balance. We have shown that BN 52021 exerts only partial protecting effect against Na-TC-induced AP in rats. The positive effects of BN 52021 were expressed by: (1) Significant reduction of hyperamylasemia accompanied by lower malondialdehyde accumulation in pancreatic tissue; (2) Prevention of sulfl hydryl groups depletion in lung tissue; (3) Diminution of necrotic and inflammatory changes in pancreatic tissue; and (4) Improvement of survival rate. We suggest that these effects may depend on the inhibition of PAF-mediated activation and oxidant generation by phagocytes.     

Effects of PAF antagonist, BN52021, on the PAF-, methacholine-, and allergen-induced bronchoconstriction in asthmatic children

Platelet-activating factor (PAF) is an inflammatory mediator capable of inducing protracted inflammation of the airways and bronchial hyperreactivity. Twenty-one asthmatic children were evenly divided into three groups and each group performed a double-blind, placebo-controlled and crossover study on the effect of aerosolized BN52021, a PAF antagonist, on the bronchoconstriction induced by PAF, methacholine, or specific allergen, respectively. One group of healthy children was included for comparison. Total WBC, neutrophils, and eosinophils were counted before and after PAF challenge. The results showed the following: (1) six of seven asthmatics and one of seven normal subjects gave a positive bronchial provocation with PAF; (2) in asthmatics, prior inhalation of BN52021 could inhibit the bronchoconstriction induced by PAF (6/6) and allergen (3/7), but not by methacholine; and (3) 5 min after inhalation of PAF, there was a marked decrease of peripheral blood eosinophils and neutrophils that could be inhibited by prior inhalation of BN52021 in normal subjects but not in asthmatics. These findings support the idea that PAF may be involved in the pathogenesis of bronchial asthma and PAF antagonist may have a role in the prevention and treatment of this disease.     

The effect of platelet activating factor antagonist (BN 52021) on cerulein-induced acute pancreatitis with reference to oxygen radicals

Acute edematous pancreatitis was induced in Wistar male rats by iv infusion of cerulein (CR) in the dose of 5.10(-6)g.kg-1.h-1 during 3 or 6 h. The effect of BN 52021--platelet activating factor (PAF) receptor antagonist, against this model of disease was examined. BN 52021 was applied iv as a bolus injection in the dose of 5.10(-3)g.kg-1 at 0 time. Treatment with this agent significantly ameliorates cerulein-induced acute pancreatitis in rats. The effect of BN 52021 was expressed by significant reduction of pancreas edema, diminution of hyperamylasemia, lack of superoxide dismutase activity depletion, and inhibition of lipid peroxidation in pancreatic tissue. These changes were accompanied by significant reduction of acinar cells vacuolization and remarkable inhibition of infiltration with inflammatory cells in the interacinar space. We suppose that beneficial effect of BN 52021 against cerulein-induced acute pancreatitis in rats depends on the prevention of inflammatory cells activation and subsequent generation of oxygen radicals within pancreatic tissue.     

Protective effect of BN 52021, a specific antagonist of platelet-activating factor (PAF-acether) against diet-induced cholesteryl ester deposition in rabbit aorta

Platelet-activating factor (PAF-acether), a phospholipid mediator involved in inflammatory reactions, has been reported to induce endovascular surface lesions. We investigated the possible involvement of PAF-acether in the mechanism of arterial cholesterol deposition. Rabbits fed a normal or hypercholesterolic diet were treated orally for 1 month with BN 52021 (20 mg/kg per day), a specific PAF-acether antagonist, and killed at the end of treatment. Cholesterol feeding resulted in a marked (50-fold) increase in plasma cholesterol. However, the drug had no significant effect on the diet-induced hypercholesterolemia. Free and esterified cholesterol were markedly increased (635%) in the aorta of animals receiving the atherogenic diet. This accumulation was reduced by 36% upon simultaneous administration of BN 52021 (P less than 0.02, n = 15). This decrease essentially affected the esterified cholesterol content. Conversely, BN 52021 showed no effect on the cellular cholesterol esterification, since liver acyl-CoA: cholesterol acyltransferase activity remained unchanged. This study indicates that BN 52021 is effective in reducing cholesterol accumulation in rabbit atherosclerotic aorta, without changing the plasma cholesterol levels.