硝苯吡啶抗动脉粥样硬化的实验研究——Ⅰ对主动脉壁病变的影响

我们观察了硝苯吡啶对饲喂高胆固醇饮食诱发实验性兔动脉粥样硬化的作用。结果发现,硝苯吡啶(10mg/kg/day,皮下注射,共8周)对高脂饮食诱导的高胆固醇血症没有作用,但对主动脉粥样病变有影响,高脂对照组主动脉病变面积平均达9.620±1.267%,动脉壁干组织胆固醇含量12.697±1.239mg/g;而采用硝莱吡啶处理的动物(?)分别为2.866±1.872%(P<0.01)和6.442±1.133mg/g(P<0.005),表明硝苯吡啶具有明显的抗动脉粥样硬化作用。     

番茄红素对动脉粥样硬化兔血脂的调节作用

目的研究番茄红素(lycopene)对动脉粥样硬化兔血脂的调节作用。方法21只新西兰大白兔,♀♂不拘,随机分为正常对照组、高脂模型组(胆固醇组)、番茄红素预防干预组(药物组),分别饲喂标准、标准+胆固醇、标准+胆固醇+番茄红素的颗粒饲料,于实验开始前1d和开始后第4、8、10wk末取空腹血,检测血清甘油三酯(TG)、总胆固醇(TC)和高密度脂蛋白胆固醇(HDLC)。10wk末取血后处死,取主动脉、肝脏做病理形态学观察。所有数据经SPSS10.0软件进行统计分析。结果与胆固醇组比较,药物组的TG在第10wk时降低(P<0.01)。病理分析,主动脉的苏丹Ⅳ大体观察显示,药物组的主动脉脂质斑块面积较胆固醇组减少,脂肪肝的程度也较胆固醇组减轻。结论番茄红素可以防止或延缓新西兰兔大血管动脉粥样硬化病变的形成,其机制除抗氧化以外,还可能与调血脂、降低甘油三酯浓度有关。     

硝苯吡啶抗动脉粥样硬化的实验研究——Ⅲ、对血清、主动脉和心肌 Ca~(2+)含量的影响

本实验观察了硝苯呲啶对实验性动脉粥样硬化家兔血清、主动脉和心肌 Ca~(2+)的影响。结果表明硝苯吡啶对血清和心肌 Ca~(2+)影响较小,但能降低高脂刺激所增加的主动脉 Ca~(2+)水平,这可能是硝苯呲啶抗动脉粥样硬化的机制之一。     

复方旱莲叶碳化剂止血机理的实验性研究──Ⅰ、对凝血机制和血小板功能的影响

本文从凝血机制和血小板功能方面探索复方旱莲叶碳化剂止血作用的可能机理。结果表明，复方旱莲叶碳化剂导致止血过程所需时间缩短，不是通过影响凝血机制所致，而与诱导血小板ＭＤＡ产生增多有关。     

肥大细胞对平滑肌源性泡沫细胞Ⅰ型胶原和Ⅲ型胶原表达的影响

目的　检测大鼠腹腔肥大细胞(mastcell,MC)对平滑肌源性泡沫细胞Ⅰ型胶原和Ⅲ型胶原表达的影响。方法　SD大鼠体重约2 0 0g ,雌雄不限,供采集MC和原代培养平滑肌细胞(smoothmusclecell,SMC)。采用梯度密度离心分离MC ,提取MC上清液(含MC释放的各种炎症介质)。用MC上清液和氧化型低密度脂蛋白(oxLDL)处理SMC ,实验分四组:对照组SMC在5mL含10 %小牛血清的DMEM中培养4 8h ;oxLDL组SMC在5mL含10 %小牛血清的DMEM中(含oxLDL ,终浓度为10 0mg L)培养4 8h ;MC上清液组SMC在5mL含10 %小牛血清的MC上清液(由含1×10 6 个MC的细胞悬液提取)中培养4 8h ;MC上清液+ox LDL组SMC在5mL含10 %小牛血清的MC上清液(由含1×10 6 个MC的细胞悬液提取)中(含oxLDL ,终浓度为10 0mg L)培养4 8h。采用油红O染色检测SMC泡沫化。RT PCR检测SMCⅠ型胶原和Ⅲ型胶原mRNA的表达,PCR引物序列Ⅰ型胶原为5′GACACTGAACCCTTTGTAATG 3′和5′GTGAAACTCCCGTCTGCT 3′,扩增片段长度为399bp ;Ⅲ型胶原引物序列为5′AGCGGAGAATACTGGGTT 3′和5′TGTAATGTTCTGGGAGGC 3′,扩增片段长度为2 88bp ;内参照采用βactin ,引物序列为5′GTGGGGCGCCCCAGGCACCA 3′和5′CTCCTTAATGTCACGCACGATTTC 3′,扩增片段长度为5 4 8bp。免疫细胞化学染色检测SMCⅠ型胶原和Ⅲ型胶原蛋白表达。结果　油红O染色显示MC上清液可加速SMC泡沫化。RT PCR结果发现,与对照组SMC相比,用oxLDL或MC上清液分别单独处理SMC 4 8h后,Ⅰ型胶原和Ⅲ型胶原的mRNA表达均降低,用oxLDL和MC上清液同时处理SMC 4 8h后,Ⅰ型胶原和Ⅲ型胶原的mRNA表达降低更明显。免疫细胞化学染色显示,对照组SMC细胞浆内有大量棕色颗粒,颗粒粗大而染色深,说明对照组Ⅰ型胶原和Ⅲ型胶原的蛋白表达为强阳性;用oxLDL或MC上清液分别单独处理SMC 8h后,细胞浆内棕色颗粒少而染色浅,说明Ⅰ型胶原和Ⅲ型胶原的蛋白表达均明显降低;用oxLDL和MC上清液同时处理SMC 4 8h后,Ⅰ型胶原和Ⅲ型胶原的蛋白表达降低更明显。结论　MC在体外抑制SMCⅠ型胶原和Ⅲ型胶原表达,并且能协同oxLDL对Ⅰ型胶原和Ⅲ型胶原表达的抑制作用。因此MC释放的炎症介质也许参与了动脉粥样斑块纤维帽的重构。     

复方旱莲叶碳化剂止血机理的实验性研究──Ⅱ、对血管平滑肌收缩功能的影响

本研究观察到，复方旱莲叶碳化剂可引起血管平滑肌收缩，而且不被酚妥拉明阻断。联系以前的工作，复方旱莲叶碳化剂的这种作用，可能是导致其止血效果较好的主要机制。     

昆明种小鼠腹膜巨噬细胞源性泡沫细胞模型的建立

本实验选用昆明种小鼠，探索了其腹膜巨噬细胞的最佳收集时间，并且将这些巨噬细胞置于２０ｇ·Ｌ~（－１）氧化低密度脂蛋白中孵育４天，在电镜下可能观察到细胞的泡沫样改变，提示昆明种小鼠腹膜巨噬细胞在一定条件下可能转变为病理性的巨噬细胞源性泡沫细胞。     

异烟肼和磺胺二甲嘧啶乙酰化的相关性

353名汉族受试者中,INH慢型为74人,占20.96％;快、慢分型无性别差异。服SM_282人,慢型为16人,占18.3％。随机研究本批中的56人,在服SM_2一个月后服INH,两药快慢型吻合率达87.50％。INH和SM_2药代动力学均呈时间节律,两药均在22∶00～2∶00时,代谢比率最低;而在10∶00～14∶00时,代谢比率最高,在INH快型的结核病患者,建议采用晚上顿服INH,可望比白天顿服获得更佳疗效和最小的肝脏毒性。     

微量内毒素对兔血脂水平影响的初步实验研究

本文观察了微量内毒素注射对兔血脂水平的影响。结果表明：一次静脉内毒素注射，兔血浆总胆固醇（ＴＣ）、ＨＤＬ胆固醇（ＨＤＬ－Ｃ）和甘油三酯（ＴＧ）水平无显著改变，重复多次微量内毒素注射可引起高脂兔血浆ＨＤＬ－Ｃ显著降低。提示内在素可通过影响血脂代谢而与动脉粥样硬化的形成和发展存在一定的联系。     

Transgenic mice with overexpression of human scavenger receptor A on endothelial cells

Objectives To establish a new transgenic mouse model for determining the function and role of human scavenger receptor A (SR- A) in atherosclerosis in vivo. Methods Human scavenger receptor minigene- driven mouse tie- 1 promoter was constructed and confirmed by endonuclease digestion and sequence analysis. Transgenic mice were generated via the microinjection method. PCR and Southern blot were used t o screen the positive transgenic mice. RT- PCR and immunohistochemical analysis were used to detect the level and location of human SR- AⅠ expression in transgenic mice. The activity of human SR- AⅠ was determined by morphologi c observation of aortic endothelial cells of transgenic mice under transmission electron microscopy. Results The electrophoresis assay showed the expected 4 fragments of 0. 9 kb, 1. 1 kb, 1. 2 kb and 4. 2 kb in the SmaⅠ digest and 2 fragments of 0. 8 kb and 6 . 7 kb in BglⅡ digest of plasmids pTie- 1/hSR- A. The fragment sequence of tie - 1 p romoter and human SR- A cDNA in plasmids pTie- 1/hSR- A was correct and no A TG b efore the translation initiation sites of human SR- A was found by sequence ana lysis. 561 injected and surviving embryos with the purified human SR- A minigen e were implanted into the oviducts of 19 ICR pseudopregnant mice. Among the 54 surviving pups from 13 foster mothers, 7 were identified by PCR and Sou thern blot analysis. The results of RT- PCR and immunohistochemical analysis sh owed human SR- A was specifically expressed on vascular endothelial cells of the aorta and renal artery, as well as hepatic sinusoidal endothelial cells in tran sgenic mice. Transmmion electron microscope (TEM) of aorta of transgenic mice s howed that a large number of vesicles, multivesicle bodies and swollen mitochond ria filled the plasma of endothelial cells. Conclusions A transgenic mouse model with overexpression of human SR- A in endothelial cells was successfully established. The transgene was integrated and transmitted int o the chromosome of transgenic mice. Tie- 1 promoter controlled the transgene t o express in endothelial cells in mice. Pinocytic activity of aortic endothelia l cells in transgenic mice was higher than that of C57BL/6J mice. Our studies w ill provide a new transgenic model for investigation of atherosclerosis and func tions of human SR- A.