细胞相互作用对PAF、系膜细胞paf-R基因表达的影响及阿托伐他汀的干预作用

目的:探讨高糖高脂条件下内皮细胞与系膜细胞相互作用对PAF产生、系膜细胞paf-R基因表达的影响及阿托伐他汀的干预作用。方法:内皮细胞与系膜细胞共培养和系膜细胞单独培养后随机,分为对照组、甘露醇组、高糖高脂组、阿托伐他汀组,培养24h后,ELISA法检测各组细胞上清液PAF含量,实时荧光定量检测系膜细胞paf-RmRNA表达。结果:(1)高糖高脂促进共培养组和单培养组PAF升高(P0.05),共培养组PAF均较单培养组升高(P0.05);(2)高糖高脂可上调系膜细胞paf-R mRNA表达(P0.05);(3)共培养和单培养条件下,阿托伐他汀可抑制高糖高脂引起的PAF升高(P0.05),并可抑制高糖高脂引起的系膜细胞paf-RmRNA表达上调(P0.05)。结论:(1)高糖高脂环境下,系膜细胞和内皮细胞存在异常的相互作用,这种作用促进PAF产生;(2)高糖高脂促进系膜细胞paf-R基因表达,使PAF的生物效应进一步放大;(3)阿托伐他汀可影响高糖高脂条件下内皮细胞与系膜细胞之间的相互作用。     

高糖高脂对系膜细胞产生细胞外基质及PAF的影响

目的： 探讨高糖高脂对系膜细胞产生细胞外基质（ECM）和血小板活化因子（PAF）的影响。方法：人系膜细胞单独培养,分为对照组、甘露醇组、高糖高脂组、PAF受体拮抗剂BN52021+高糖高脂组, ELISA法检测各组细胞上清液中纤维连接蛋白（Fn）、IV型胶原（Col IV）、血小板活化因子（PAF）含量,实时荧光定量检测系膜细胞血小板活化因子受体（PAF-R） mRNA表达。结果：高糖高脂可引起系膜细胞培养上清液Fn和Col IV含量升高（均P<0.05）,BN52021可抑制高糖高脂引起的Fn和Col IV含量升高（P<0.05）;高糖高脂可引起系膜细胞培养上清液PAF含量升高（P<0.05）;高糖高脂可上调系膜细胞PAF-R mRNA表达（P<0.05）。结论: 高糖高脂刺激系膜细胞Fn、Col IV、PAF产生,高糖高脂刺激的ECM分泌增加部分与PAF有关; 高糖高脂可促进系膜细胞PAF-R基因表达,使PAF的生物效应进一步放大。     

阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响

目的　探讨阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响。 方法　28只成年SD大鼠,给予高脂饮食8周,建立结扎股动脉诱导的高胆固醇血症大鼠侧支血管生长模型。随机将动物分为单纯股动脉结扎组（L组）、高胆固醇血症+股动脉结扎组（HL组）和阿托伐他汀（0.3 mg·kg-1·14 d-1,腹腔注射）+高胆固醇血症+股动脉结扎组（AL组）。存活7 d后,采用血管造影,HE染色和共聚焦免疫荧光术,观察高胆固醇血症情况下,阿托伐他汀应用对侧支血管生长的作用以及重要的促侧支血管生长分子在侧支血管表达模式的变化。 结果　与L组比较,HL组的侧支血管数目减少,侧支血管生长受到损害,表现为血管内膜过度增生,中膜明显增厚,导致血管腔狭窄,且血管壁细胞增殖和外膜炎症细胞减少;AL组应用了阿托伐他汀,侧支血管的生长较HL组明显改善,发育为管腔较大的侧支血管,血管壁细胞的增殖和外膜炎症细胞增多,侧支血管数目增加。其侧支血管数目,血管横截面积和免疫荧光强度差异具有统计学意义（P<0.05）。 结论　高胆固醇血症损害大鼠后肢侧支血管的生长;阿托伐他汀可促进血管壁细胞的增殖和外膜巨噬细胞的增多,从而改善和恢复侧支血管的生长。     

阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响

目的　探讨阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响。 方法　28只成年SD大鼠,给予高脂饮食8周,建立结扎股动脉诱导的高胆固醇血症大鼠侧支血管生长模型。随机将动物分为单纯股动脉结扎组（L组）、高胆固醇血症+股动脉结扎组（HL组）和阿托伐他汀（0.3 mg·kg-1·14 d-1,腹腔注射）+高胆固醇血症+股动脉结扎组（AL组）。存活7 d后,采用血管造影,HE染色和共聚焦免疫荧光术,观察高胆固醇血症情况下,阿托伐他汀应用对侧支血管生长的作用以及重要的促侧支血管生长分子在侧支血管表达模式的变化。 结果　与L组比较,HL组的侧支血管数目减少,侧支血管生长受到损害,表现为血管内膜过度增生,中膜明显增厚,导致血管腔狭窄,且血管壁细胞增殖和外膜炎症细胞减少;AL组应用了阿托伐他汀,侧支血管的生长较HL组明显改善,发育为管腔较大的侧支血管,血管壁细胞的增殖和外膜炎症细胞增多,侧支血管数目增加。其侧支血管数目,血管横截面积和免疫荧光强度差异具有统计学意义（P<0.05）。 结论　高胆固醇血症损害大鼠后肢侧支血管的生长;阿托伐他汀可促进血管壁细胞的增殖和外膜巨噬细胞的增多,从而改善和恢复侧支血管的生长。     

高脂饮食及阿托伐他汀干预对主动脉瓣膜内皮细胞表面超微结构的影响

目的利用原子力显微镜观察高脂饮食及阿托伐他汀干预对主动脉瓣膜内皮细胞表面形态结构的影响。方法新西兰纯种雄性白兔60只,随机分为对照组、高脂饮食组、高脂饮食＋阿托伐他汀干预组,每组各20只。分别于实验开始及第2、4、6、8周末5个时间点,将上述3组动物各随机处死4只,取其心脏主动脉瓣膜,标本经处理后,置于原子力显微镜下扫描观察。结果随着高脂饮食时间的延长,高脂饮食组瓣膜表面内皮细胞的排列从规则的栅栏状密集的排列,逐渐过渡到无序紊乱的疏松排列。细胞形态从长梭形逐渐过渡为短圆形,细胞之间的间隙逐渐扩大。当AFM在内皮细胞表面的扫描范围进一步缩小时,随着高脂饮食时间的延长,内皮细胞表面大小一致,均匀排列的球形隆起结构逐渐变得低平、融合、减少;高脂饮食及阿托伐他汀干预组内皮细胞的改变介于对照组和高脂饮食组两组之间。结论利用AFM能够在瓣膜组织原位清晰显示损伤保护作用后,内皮细胞膜表面三维超微结构的变化;高脂饮食可以使主动脉瓣膜内皮细胞的排列、分布、形态发生明显改变,为后期与高脂血症有关的瓣膜疾病,例如钙化性主动脉瓣膜狭窄的发生提供条件。阿托伐他汀能够缓解高脂饮食所致的主动脉瓣膜内皮细胞形态结构的改变。     

阿托伐他汀改善蛛网膜下腔出血患者的预后分析

目的 对阿托伐他汀可降低脑损伤标记物并减少SAH后脑血管痉挛的发生率进行研究。方法 选取2015年1月~12月本院经血管造影明确诊断血管瘤破裂导致的自发性SAH且发病48 h内的患者40例,将其随机分为对照组和阿托伐他汀组,每组20例。对照组给予保护脑神经,预防脑血管痉挛等常规治疗;阿托伐他汀组在对照组常规治疗的基础上给予阿托伐他汀,每周记录谷丙转氨酶,谷草转氨酶以及肌酸激酶评估肝损伤及肌损伤。每天记录脑损伤标记物变化情况。记录血管造影或经颅多普勒测量大脑中动脉血流峰值超过160 m/sec为发生血管痉挛的指标。结果 阿托伐他汀组与对照组肝损伤及肌损伤发生率比较,差异无统计学意义（P＞0.05）。阿托伐他汀组血清中vWF因子平均浓度11.95 ng/ml,低于对照组21.59 ng/ml,差异有统计学意义（P＜0.05）;阿托伐他汀组血清中S100β因子平均浓度50.8 pg/ml,低于对照组190.5 pg/ml,统计学意义显著（P＜0.01）。经颅多普勒大脑中动脉血流峰值阿托伐他汀组（103.11±41.01)m/sec,低于对照组（149.12±48.12）m/sec,统计学意义显著（P＜0.01）。阿托伐他汀组血管痉挛发生率 25.00%,低于对照组60.00%,差异有统计学意义（P＜0.05）。结论 自发性蛛网膜下腔出血患者及早使用阿托伐他汀可明显较少血管痉挛的发生率,并具有良好的安全性及耐受性。阿托伐他汀可降低血清中SHA脑损伤标记物,减少血管痉挛,减轻迟发型缺血性损伤,改善SAH患者预后。     

阿托伐他汀对脂多糖诱导人脐静脉内皮细胞Toll样受体4及其下游信号转导通路的影响

背景：研究表明Toll样受体4参与了动脉粥样硬化的发生和发展,目前Toll样受体4与MyD88依赖性或MyD88非依赖性信号转导通路在动脉粥样硬化发生和发展中的机制尚不明确。 目的：观察阿托伐他汀对脂多糖诱导的人脐静脉内皮细胞Toll样受体4及其下游信号转导通路主要元件MyD88、TRAF-6、TRAM及TRIF表达的影响,分析阿托伐他汀防治动脉粥样硬化的机制。 方法：体外培养人脐静脉内皮细胞,用脂多糖刺激并加入阿托伐他汀干预24 h,收集细胞,用荧光定量PCR方法测定TLR4、MyD88、TRAF-6、TRAM及TRIF mRNA表达;用Western blotting法测定TLR4、MyD88及TRAF-6蛋白表达。 结果与结论：用脂多糖刺激人脐静脉内皮细胞后,引起TLR4、MyD88、TRAF-6、TRAM和TRIF的高表达(P < 0.01),用阿托伐他汀干预后可显著抑制TLR4、MyD88及TRAF-6的表达(P < 0.01)。提示阿托伐他汀可阻断Toll样受体4高表达,同时阻断Toll样受体4胞内信号转导的MyD88依赖性途径,这可能是阿托伐他汀抗动脉粥样硬化的作用机制之一。     

香烟提取物损伤人脐静脉血管内皮细胞及阿托伐他汀的干预

背景：吸烟是诸多血管缺血性疾病如动脉硬化闭塞、血栓闭塞性脉管炎等疾病的重要危险因素,但其确切机制尚不清楚。 目的：探讨香烟提取物对人脐静脉内皮细胞的影响以及阿托伐他汀对该作用的干预。 方法：将体外培养的人脐静脉内皮细胞分为3组,分别以含体积分数10%胎牛血清的DMEM培养基对照组、体积分数10%胎牛血清+10%香烟提取物的DMEM培养基、含体积分数10%胎牛血清+10%香烟提取物+10 μmol/L阿托伐他汀的DMEM培养基培养。 结果与结论：香烟提取物组人脐静脉内皮细胞形态较对照组不规则,存活率、细胞上清液中的一氧化氮水平和细胞一氧化氮合酶活性降低(P < 0.05);香烟提取物+阿托伐他汀组使人脐静脉内皮细胞形态改善,存活率、细胞上清液中的一氧化氮水平和细胞一氧化氮合酶活性升高(P < 0.05)。说明阿托伐他汀能拮抗香烟提取物对血管内皮细胞的损伤作用,其机制可能与内皮细胞的生长、一氧化氮合成酶活性及一氧化氮释放有关。     

通心络超微粉对高脂饮食兔主动脉内皮保护机制的实验研究

目的： 探讨通心络超微粉对高脂饮食兔主动脉内皮损伤的干预作用及其可能机制。方法： 健康雄性新西兰白兔32只随机分为空白对照组、模型组、阿托伐他汀组、通心络组4组。空白对照组饲以普通饲料；模型组饲以高脂饲料；阿托伐他汀组饲以高脂饲料同时阿托伐他汀3 mg·kg^-1·d^-1灌胃；通心络组饲以高脂饲料同时通心络超微粉0.31 g·kg^-1·d^-1灌胃，连续给药，于6周末酶法检测各组血脂水平，比色法检测各组血清NO、MDA水平及SOD活性，免疫组织化学染色法检测主动脉内皮细胞NF-κB核转位情况及ICAM-1 蛋白表达，RT-PCR法检测ICAM-1 mRNA表达。结果：模型组血清TC、TG、LDL-C、HDL-C及MDA水平均显著高于空白对照组(P<0.01)，NO水平及SOD活性低于空白组(P<0.01)；主动脉内皮细胞NF-κB核转位、ICAM-1基因及蛋白表达明显多于空白组（P<0.01）。两药物干预组TC、TG、LDL-C及MDA水平均显著低于模型组(P<0.01)，NO水平和SOD活性则高于模型组（P<0.05, P<0.01），主动脉内皮细胞NF-κB核转位、ICAM-1基因及蛋白表达亦明显少于模型组（P<0.05，P<0.01），通心络组HDL-C显著高于模型组（P<0.05），且通心络组对上述指标的作用均优于阿托伐他汀组（P<0.05，P<0.01）。结论： ① 高脂血症可使血管内皮细胞受损，其机制可能与氧化应激、NF-κB的激活及ICAM-1基因与蛋白的表达异常有关。② 通心络超微粉可在一定程度上减轻上述病理损伤，可能与其抗氧化、抑制NF-κB核转位进而降低ICAM-1基因及蛋白表达有关。     

利拉鲁肽抑制高糖诱导大鼠肾小球系膜细胞株TNF-a和ICAM-1表达

 目的 探讨高糖对大鼠肾小球系膜细胞(RGMC) 中TNF-a和ICAM-1表达影响以及利拉鲁肽的干预作用。方法 将培养的RGMC 株分为6 组,分别为：对照组、高糖刺激组、Liraglutide（Li）低 、中和高浓度( 10、100和1 000nmol /L) 干预组,以及吡咯烷二硫代氨基甲酸盐( PDTC) 干预组。用ELISA 法测定肾小球系膜细胞TNF-a 以及ICAM-1蛋白表达,用RT-PCR法测定系膜细胞TNF-a 以及ICAM-1基因表达。结果高糖可上调RGMC 中TNF-a、ICAM-1蛋白及基因表达（P均<0.05）,利拉鲁肽可抑制高糖诱导下RGMC 中TNF-a、ICAM-1蛋白及基因表达（P均<0.05）。与高糖刺激组比较,PDTC组TNF-a、ICAM-1表达量减少（P<0.05）。结论 利拉鲁肽在一定程度上减轻高糖诱导下RGMC 中TNF-a和ICAM-1的表达,可能发挥一定的肾脏保护作用。     

血小板活化因子受体在SAP胰腺组织的变化及银杏苦内酯B的影响

目的探讨血小板活化因子受体(PAF-R)在重症急性胰腺炎(SAP)胰腺组织的动态变化及银杏苦内酯B(BN52021)干预前后的影响。方法Wistar大鼠随机分为阴性对照组(NC组)、SAP模型组(SAP组)、BN52021治疗组(BN组),每组按手术后不同时相点(1、2、3、6、12和24h)分为6小组,分别测定血淀粉酶的变化,并对胰腺组织进行病理学观察和评分,用Westernblot检测胰腺组织PAF-R蛋白质表达的变化。结果BN52021能降低SAP的血淀粉酶和改善其病理变化;SAP组和BN组胰腺组织PAF-R在3h达到高峰(P<0.05),除1h外其余各时相点与NC组有显著性差异(P<0.05);BN组与SAP组之间无显著性差异。结论PAF-R在SAP过程中显著升高,对SAP的病情发展有重要意义,BN52021对PAF-R蛋白表达无显著影响,可能通过竞争性抑制上升的PAF与表达量同时上升的PAF-R相结合,实现它的治疗作用。     

The effect of the platelet-activating factor antagonist, BN 52021, on human natural killer cell-mediated cytotoxicity.

The influence of the platelet-activating factor (PAF) antagonist, BN 52021, on human natural killer (NK) cell cytotoxicity against K 562 target cells was determined. Cytotoxicity was measured by a short-term (4 hr) 51Cr-release assay. The cytotoxicity was significantly reduced in the presence of PAF antagonist at concentrations from 30 to 120 microM. This reduction of killing was not due to the impairment of binding of effector cells to target cells. Pretreatment of K 562 target cells with the PAF antagonist led to a greater inhibition of NK cell cytotoxicity compared with that observed when the effector cells were preincubated with BN 52021. Thus, the inhibition of cytotoxicity appears to be due to an effect of BN 52021 on target cells rather than on lymphocytes. Furthermore, the increase in NK activity induced by interferon was less pronounced when BN 52021 was added in the incubation medium. The natural cytotoxicity of platelet-depleted or large granular lymphocyte-enriched effector cell populations was inhibited by the PAF antagonist in a similar manner. The effect of BN 52021 appears to be related to its specific PAF antagonistic activity since a similar action on NK cells was noted with two other structurally unrelated PAF antagonists, BN 52111 and WEB 2086. In contrast, Ginkgolide J (BN 52024), which is structurally related to BN 52021 but lacks PAF antagonistic activity, was ineffective in inhibiting NK cell cytotoxicity. Finally, synthetic PAF induces a dose-dependent cytotoxic action on K 562 cells and this effect of the autacoid is inhibited by BN 52021. These observations provide indirect evidence that PAF could play a role in the mechanism(s) of NK cytotoxity.     

Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor

Platelet-activating factor (PAF), a bioactive lipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A(2) and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 +/- 14%, mean +/- SE; n = 32) when compared with that in wild-type mice (219 +/- 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 microM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 microM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity.     

Effects of the platelet-activating factor antagonist BN 52021 on anti-islet cytotoxicity of mononuclear cells and serum from type 1 (insulin-dependent) diabetic patients

The effect of platelet-activating factor (PAF) antagonist BN 52021 (0.06-2.5 mM) on the cytotoxic activity of mononuclear cells (MNC) from newly diagnosed type 1 diabetic patients against 51Cr-labeled Langerhans islets from neonatal rats was investigated in a 6-hour cytotoxicity test. A dose-dependent inhibition of anti-islet cytotoxicity by BN 52021 was observed. The suppression of the islet lysis was significant at a concentration of 0.6 mM BN 52021. During a 4-day cell culture, BN 52021 had no inhibitory effect on the antigen-mediated triggering of immunocytes with anti-islet cytotoxicity. The results suggest that the drug is only effective during immunocytolytic reactions of MNC against pancreatic islets. A PAF-independent action of BN 52021 can not be excluded at present.     

Effect of the platelet-activating factor antagonist BN 52021 on human natural killer cell cytotoxicity

The possible role of platelet-activating factor (PAF) in natural killer (NK) cell cytotoxicity was investigated by examining the effect of the PAF antagonist BN 52021 in NK cytotoxicity towards 51Cr-labelled K 562 target cells. When BN 52021 (30-120 microM) was added during the assay, a dose-dependent inhibition of NK activity was observed. The inhibition of cytotoxicity by BN 52021 was not due to an alteration of the binding of lymphocytes to K 562 cells. When lymphocytes were preincubated with BN 52021 (60 microM) for 60 min before the target cells were added, the inhibitory effect of the drug was similar to that observed when it was added at the start of the reaction. Inhibition was more pronounced when the target cells were pretreated for 60 min before the start of the assay. BN 52021 (60 microM) also inhibited gamma interferon induced NK activity. These studies provide indirect evidence that NK cells can generate PAF and that this mediator is involved in cytotoxic processes.     

霉酚酸酯对高糖培养下人肾小球系膜细胞MCP-1和FN表达的影响

目的:探讨高糖以及霉酚酸酯(MMF)对人肾小球系膜细胞(HMCs)单核细胞趋化蛋白-1(MCP-1)和纤维连接蛋白(FN)表达的影响。方法:将培养的HMCs分为正常对照组(5 mmol/L葡萄糖);高糖组(30 mmol/L葡萄糖);甘露醇渗透压对照组(5 mmol/L葡萄糖+25 mmol/L甘露醇);高糖+MMF-10组(30 mmol/L葡萄糖+10μg/mL MMF);高糖+MMF-100组(30 mmol/L葡萄糖+100μg/mL MMF),采用RT-PCR检测每组不同时间点(24、48、72 h)MCP-1 mRNA的表达,ELISA法检测培养上清液MCP-1及FN蛋白的表达。结果:高糖组HMCs MCP-1 mRNA、蛋白的表达及FN的分泌较正常对照组显著增加(P<0.01),且48 h表达最高;不同浓度的MMF均能下调MCP-1 mRNA、蛋白及FN的表达(P<0.01);不同浓度的MMF对MCP-1 mRNA、蛋白的表达及FN分泌的抑制程度不同,呈时间剂量依赖性(P<0.05)。结论:MMF可以阻抑MCP-1的表达及FN的分泌,可能对延缓肾小球硬化及间质纤维化有一定作用。     

活性氧介导高糖负荷致人系膜细胞癌胚纤维连接蛋白的表达

背景：研究发现,癌胚纤维连接蛋白系新合成细胞外基质的重要标志,而高糖环境氧化应激与癌胚纤维连接蛋白的关系尚未见报道。 目的：观察高糖作用对人系膜细胞活性氧和癌胚纤维连接蛋白mRNA表达的影响。 方法：将培养的系膜细胞分为以下各组：正常对照组(5 mmol/L D-葡萄糖);渗透压对照组(5 mmol/L D-葡萄糖+           20 mmol/L L-葡萄糖);高糖组(25 mmol/L D-葡萄糖);α-硫辛酸干预组,分为高糖+LA50组(25 mmol/L D-葡萄糖+        50 μmol/L α-硫辛酸)、高糖+LA100组(25 mmol/L D-葡萄糖+100 μmol/L α-硫辛酸)、高糖+LA200组(25 mmol/L D-葡萄糖+  200 μmol/L α-硫辛酸)。以RT-PCR法检测癌胚纤维连接蛋白mRNA表达水平,荧光显微镜和荧光酶标仪测定细胞内活性氧水平。 结果与结论：高糖促进系膜细胞活性氧的产生,亦增加癌胚纤维连接蛋白mRNA的表达,α-硫辛酸可显著降低高糖负荷下细胞内活性氧水平,同时减少癌胚纤维连接蛋白mRNA的表达,且呈浓度依赖性,提示活性氧介导高糖负荷致人系膜细胞癌胚纤维连接蛋白的表达,α-硫辛酸可部分逆转这一效应。     

Protection of platelet-activating factor-induced acute renal failure by BN 52021.

Although platelet-activating factor (PAF) is a well-known mediator in experimental shock, its precise role in acute renal failure remains to be defined. Male Wistar rats (209 +/- 12 g) were placed in individual metabolic cages for 24 h before i.v. injection of PAF (2-6 micrograms/kg). Injection of 6 micrograms/kg PAF proved lethal and use of such a high dose was thus discontinued. Administration of 2 micrograms/kg and 4 micrograms/kg PAF resulted in a fall of glomerular filtration rate (GFR) associated with a reduction in urinary flow rate (UFR). Rats pretreated with BN 52021 (25 mg/kg p.o.) exhibited values of GFR similar to that of the control group, but not after 4 micrograms/kg PAF. In addition, in the group of BN 52021 pretreated rats and injected with 2 micrograms/kg or 4 micrograms/kg PAF, UFR was not significantly different from that of the control group at 24 h. Examination by electron microscopy revealed the presence of platelets in the glomeruli, as well as loss of fixed anionic charges in PAF injected rats. The presence of these platelets was not observed in rats treated with BN 52021 and injected with PAF. No changes in GFR and UFR were observed at 6 h or 24 h in vehicle or BN 52021 treated rats. Thus, BN 52021 which affords protection against acute renal failure induced by PAF may be of therapeutic value in other types of kidney disease in which this mediator is active.     

Protective effect of the PAF-antagonist BN 52021 on several models of gastro-intestinal mucosal damage in rats

Platelet-activating factor (PAF) has been shown to induce gastro-intestinal damage similar to that evoked by endotoxin, suggesting that this mediator may be involved in the formation of gastrointestinal lesions observed in various pathologies. Thus, the effects of BN 52021, a specific PAF antagonist, were investigated in several experimental models of gastro-intestinal damage in rats. BN 52021 markedly reduced the gastric alterations and almost totally abolished the intestinal lesions induced by PAF. Similarly, BN 52021 reduced gastro-intestinal damage induced by endotoxin, but it afforded less protection against endotoxin-induced changes than those caused by PAF. This difference is probably due to the multicomponent activating effect of endotoxin. In the cold restraint stress model, BN 52021 decreased both gastro-intestinal lesions and the change in plasma transaminase level. The results presented in this paper confirm the role of PAF in gastro-intestinal damage induced by endotoxin but also suggest the involvement of this mediator in stress-induced lesions. PAF-antagonists could thus be of therapeutic use in such pathologies.