多聚肌苷酸在兔动物模型中抗动脉粥样硬化的作用及对血管组织LOX-1表达的影响

目的探讨多聚肌苷酸在兔动物模型中抗动脉粥样硬化(AS)的作用以及对血凝素样氧化低密度脂蛋白-1(LOX-1)表达的抑制作用。方法 30只雄性新西兰大白兔随机分为普通饲料喂养组(对照组n=6)、球囊拉伤后高脂饲料喂养组(高脂组n=6)、球囊拉伤后高脂饲料+氟伐他汀喂养组(他汀组n=6)、球囊拉伤后高脂饲料喂养+多聚肌苷酸(polyⅠ)肌注组(polyⅠ组n=6)和球囊拉伤后高脂饲料+氟伐他汀喂养+polyⅠ肌注组(联合组n=6)。除对照组外,其余各组兔均在3%质量浓度的戊巴比妥钠全麻下经股动脉行腹主动脉球囊拉伤术损伤动脉内膜,术后开始给予高脂饲料喂养制备AS模型。各组动物均喂养12周,喂养同时每天分别给予polyⅠ[1%的质量浓度1 mL/(kg.d)]肌肉注射和氟伐他汀[10 mg/(kg.d)]喂养干预。12周后处死动物取其腹主动脉观察病理变化,用逆转录聚合酶链反应(RT-PCR)测定LOX-1 mRNA的表达;免疫组化测定LOX-1蛋白的表达。结果各组兔腹主动脉组织病理学变化:①对照组动脉血管内膜内皮细胞完整,无明显脂质沉淀;②高脂组动脉血管内膜内皮细胞脱落,可见粥样斑块形成,纤维帽下含大量无定形的坏死崩解产物,其内含大量胆固醇结晶、泡沫细胞和少量淋巴细胞;③他汀组AS程度较高脂组明显减轻,内皮细胞部分脱落,内膜下散在不规则隆起的斑块,可见数量不等的泡沫细胞;④PolyⅠ组较高脂组AS程度亦减轻,血管内膜内皮细胞部分脱落,血管可见纤维斑块和粥样斑块并存,斑块表面有纤维组织覆盖,内膜纤维帽下含大量泡沫细胞,并伴炎细胞浸润;⑤联合组病变较高脂组减轻最明显,内膜稍增厚,可见少量泡沫细胞,内弹力板完整,中膜平滑肌排列整齐。对照组兔腹主动脉血管组织中有少量的LOX-1蛋白及mRNA的表达;高脂组较其他组表达最为明显,他汀组以及联合组LOX-1蛋白和mRNA的表达较高脂组均明显减少(P均<0.01),PolyⅠ组LOX-1蛋白和mRNA的表达与高脂组差异无统计学意义(P>0.05)。结论 PolyⅠ可能具有一定的抗AS发生发展的作用,但PolyⅠ抑制LOX-1蛋白和mRNA表达的作用不显著。氟伐他汀抗AS的同时可明显地抑制血管AS斑块中LOX-1蛋白及mRNA的表达。     

Regional tyrosine hydroxylase and choline acetyltransferase concentrations in the brains of lymphocytic choriomeningitis-infected mice

The neurotransmitter biosynthesis enzymes tyrosine hydroxylase and choline acetyltransferase were investigated in selected brain areas of Nya : NYLAR mice infected with lymphocytic choriomeningitis (LCM) virus. Statistically significant alterations in the concentrations of both enzymes occurred in the olfactory, caudate, and neocortical regions at 5 days postinfection. No such alterations occurred in mice given cytoxan (150 mg/kg) 3 days postinfection and examined 5 days postinfection. At 10 days postinfection, however, the cytoxan-treated animals had significantly altered enzyme concentrations in the olfactory region, though not in the caudate or neocortex. This alteration appeared to be transitory, since it was not found in cytoxan-treated animals 60 days postinfection. A possible explanation is that virus production or interference in a brain region cycles over a period of hours or days. Still undetermined is whether these neurochemical changes are a primary effect of the virus or a secondary effect due to the immune response. It is noteworthy that cytoxan caused a marked increase in the enzyme activities studied in most of the brain areas.     

心脉神口服液抑制低密度脂蛋白体外氧化效应的实验研究

目的　探讨中成药制剂心脉神口服液 (XMSol)抑制低密度脂蛋白 (LDL)的体外氧化效应。方法　分别将不同浓度XMSol原液稀释液和服不同药量兔含XMSol血清与配好的CuSO4溶液加入LDL中共同孵育 ,测定脂质过氧化产物丙二醛 (MDA)含量 ,以评价LDL过氧化程度以及XMSol抑制LDL体外氧化效应。结果　随着XMSol原液稀释液浓度的升高MDA含量呈下降趋势 ;兔摄入XMSol药量越大 ,该组MDA生成量越少 ;各组与无XMSol的对照组相比MDA含量显著较低 (P <0 .0 1)。结论　心脉神口服液能抑制LDL的体外氧化 ,其抑制作用呈剂量依赖性。     

阿托伐他汀对不稳定型心绞痛患者巨噬细胞集落刺激因子及氧化低密度脂蛋白的影响

目的观察阿托伐他汀对不稳定型心绞痛患者巨噬细胞集落刺激因子及氧化低密度脂蛋白的影响。方法采用酶联免疫法检测试验组和对照组的血清MCSF、OX—LDL水平。结果2组治疗后各指标较治疗前有显著性差异（P〈0．05），而试验组血清MCSF、OXLDL下降幅度明显大于对照组（P〈0.05）。试验组治疗前M—CSF与OXLDL成正相关（r=0．49，P〈0．05），治疗后M—CSF下降幅度与OXLDL下降幅度亦呈正相关（r=0．61，P〈0．05）。结论阿托伐他汀可明显降低不稳定型心绞痛患者血清MCSF、OX—LDL水平，抑制了炎症过程．稳定了斑块。     

普伐他汀抑制氧化低密度脂蛋白诱导人单个核细胞TNF 和IL-8的分泌

为探讨普伐他汀对氧化修饰低密度脂蛋白（oxLDL）诱导的人外周血单个核细胞（PBMs）分泌功能的影响。在体外分离培养人PBMs，应用放免及ELISA法，检测不同浓度普伐他汀对经oxLDL诱导的单个核细胞分泌TNF-α、IL-8的影响，以及甲羟戊酸的逆转作用。普伐他汀在50μmol/L即可抑制oxLDL诱导的PBMs 分泌TNF-α、IL-8(P＜0.01)，呈浓度依赖方式；甲羟戊酸可对抗此抑制作用。普伐他汀可抑制循环血单个核细胞分泌TNF-α、IL-8，具有抗炎作用；其机制可能与普伐他汀抑制胆固醇前体物质甲羟戊酸生成有关。     

Protein in oxidized low density lipoprotein may cause injury to mitochondria of mouse peritoneal macrophages

Thedeathoffoamcellsderivedfrommacrophagescontributesmuchtotheoriginandslowenlargementofthelipidcoreofatheroma,butthecauseofthedeathofmacrophagefoamcellIsnotyetcertainllj.MacrophagesareknowntotakeupoxidizedLDL(Ox--I-DL)andsomechemicaflymodifiedLDLviascavengerreceptorstoformfoamcellsinvitroLZds4J.ComparedtochemicallymodifiedLDL,ox--LDLhasmanyadditionalcharacteristics,oneofwhichisitstoxicitytoculturedcells,suchasfibroblasts,endothelialandsmoothmusclecellsLS,6:.Ox--LDLhasalsobeenfoundtob…     

Isolation and characterization of the C3b-binding entity of C3b-receptor from human erythrocytes

Applying 2 M KBr, membranes of E^hu were solubilized. By C3-affinity chromatography an activity could be isolated that inhibited the immune adherence reaction and C3b-dependent rosette formation. Since this material did not agglutinate EAC14^oxy 23b we termed it monovalent C3b receptor (mC3bR). PAGE and SDS-PAGE and staining with Coomassie brillant blue and PAS reagent revealed a single glycoprotein band with a mol. wt. of 55,000–60,000 daltons and an electrophoretic mobility comparable to ovalbumin. This mC3bR proved to be antigenetically related to gp 205 [17]. The potential of mC3bR to react with C3b-carrying particles was not destroyed by heat and trypsin treatment but by neuraminidase or periodic acid treatment suggesting that mC3bR reacted by its carbohydrate moiety with C3b. As by mC3bR, immune adherence could be inhibited by D-glucose and D-galactose but not by their optical antipodes, L-glucose and L-galactose.     

Protection of methamphetamine nigrostriatal toxicity by dietary selenium

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (< 0.01 ppm Se) or selenium-replete (0.2 ppm Se) diets for 90 days. MA treatment decreased the dopamine (DA) levels in the striatum and substantia nigra (SN) of both Se-replete and Se-deficient animals. However, in Se-replete animals, this DA depletion was significantly attenuated in both the striatum and SN. A novel observation is that MA administration resulted in increased activity of Cu,Zn-SOD in the brains of both Se-deficient and Se-replete animals. However, MA administration to Se-deficient animals exhibited a higher Cu,Zn-SOD activity in the nigrostriatal system than the control animals. Elevated malondialdehyde (MDA) levels in the striatum and SN were also observed in Se-deficient MA-treated animals. Se repletion significantly increased the glutathione peroxidase (GPx) activity and the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the MA-treated animals. In conclusion, we have shown that dietary Se attenuated methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.