川芎嗪在豚鼠离体气管螺旋条中的作用

目的：研究川芎嗪在豚鼠离体气管螺旋条中的作用。方法：在浴槽内加入川芎嗪从10^-7 mol/L至10^-2 mol/L，观察气管螺旋条张力的变化，并检测浴槽中NO₂^-/NO₃^-含量，气管螺旋条组织cAMP、cGMP含量的变化。结果：加入川芎嗪气管螺旋条张力下降，与川芎嗪浓度呈剂量依赖性，未去皮组舒张度显著大于去皮组（P<0.01）。浴槽内NO₂^-/NO₃^-含量增加，未去皮组(2.3±0.37) mol/L升至(5.4±0.42) mol/L（P<0.05），去皮组(1.12±0.12) mol/L升至(2.29±012) mol/L（P<0 05）。气管螺旋条组织cAMP 含量增加，未去皮组(17.6±1.19) nmol/g protein升至(36.48±7.20) nmol/g protein（P<0.05） , 去皮组(8.20±2.30) nmol/g protein 升至(18.34±2.30) nmol/g protein（P<0.05），cGMP 含量增加，未去皮组(0.33±0.11) nmol/g protein 升至(0.67±0.27) nmol/g protein（P<0.05），去皮组(0.16±0.03) nmol/g protein 升至(0.33±0.16) nmol/g protein（P<0.05）。结论：川芎嗪有舒张气管螺旋条的作用。     

树鼩2型糖尿病加剧缺血性脑损伤的可能机制

目的 建立树鼩2型糖尿病（T2DM）合并脑缺血模型,探讨代谢异常加剧缺血性脑损伤的可能机制。 方法 将36只健康成年树鼩随机分为4组,即对照组、脑缺血组、T2DM组及T2DM +脑缺血组(每组n=9)。采用高脂饲养联合链脲佐菌素（STZ）注射建立实验性糖尿病模型,通过光化学反应诱导树鼩局部血栓形成,以临床症状最突出的缺血后24 h作为观察的时间点,通过血清生化指标的检测了解机体代谢状态,采用2,3,5-氯化三苯基甲氮唑（TTC）、HE染色及透射电子显微镜观察超微结构对缺血性脑损伤进行评价。 结果 树鼩T2DM和T2DM合并脑缺血组树鼩的体重有所降低［(120.29±13.82) g］,但差异无统计学意义,而血糖（FBG）、总胆固醇（TC）、低密度脂蛋白固醇（LDL-C）及甘油三酯（TG）明显升高,分别为（26.75±10.60）mmol/L、（7.40±3.26) mmol/L、（2.93±0.70）mmol/L、（1.93±0.63）mmol/L（P<0.05）和（32.29±6.08）mmol/L（7.80±3.41) mmol/L、（3.06±0.95）mmol/L和（1.73±0.29）mmol/L,（P<0.01）; 血清C-反应蛋白（CRP）水平明显升高［（1.43±0.53）mg/L,P<0.01］。糖尿病树鼩合并脑缺血时上述指标的改变更为明显,神经元受损及脑梗死面积明显增加［（19.56±1.25）%,P<0.01］。 结论 T2DM树鼩代谢异常可加剧缺血性脑损伤,其机制可能与高血糖及CRP协同作用引起的炎症反应有关。     

糖尿病肾病患者血清IL-1、IL-6含量测定

目的：检测糖尿病肾病患者血清白介素-1、白介素-6的水平,为进一步探讨与糖尿病肾病的关系提供资料。方法：2型糖尿病69例,尿白蛋白排泄率（UAE）在20-200 μg/min的21例患者为DN₁组,UAE>200 μg/min 22例患者为DN₂组,UAE<20 μg/min的26例为DM组,正常对照组20例,用免疫放射法测定血清IL-1、IL-6水平。结果：DN₂组血清IL-1含量为(31.23±6.69) ng/L,高于正常对照组[(21.37±8.24) ng/L]及DM组[(26.45±7.19) ng/L)], P<0.01, P<0.05。DM组血清IL-6含量为(1.50±0.79) μg/L,明显高于对照组（P<0.01）,DN₁组含量(1.02±0.77) μg/L,DN₂组为(0.97±0.67) μg/L,均低于DM组（两者P<0.05）。结论：糖尿病合并肾病患者血清IL-1水平高于正常对照及DM组,血清IL-6低于DM组提示其与糖尿病肾病的发病可能有一定的关系。     

丙酮酸乙酯对缺氧缺血性脑损伤新生大鼠脑组织的保护作用

 目的： 探讨丙酮酸乙酯（ethyl pyruvate, EP）对缺氧缺血性脑损伤（hypoxic-ischemic brain damage, HIBD）新生大鼠脑组织的作用及其可能机制。方法：165只7日龄SD大鼠随机分为3组:假手术组（n=43）、HIBD模型组（n=61）和HIBD+EP处理组（n=61）,造模前30 min腹腔注射EP（50 mg/kg）1次,此后每天1次,3 d后测定脑组织匀浆超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量以及脑组织含水量,TUNEL法检测脑组织凋亡细胞数;14 d后检测缺血侧和非缺血侧脑重量以判别脑萎缩程度。结果：HIBD+EP组脑组织SOD活性为(125.78±18.35)×103 U/(g protein),较HIBD模型组［(97.84±15.50)×103 U/(g protein)］明显增强（P<0.05）;MDA含量为(4.42±1.04) μmol/(g protein),较HIBD模型组［(6.02±0.89) μmol/(g protein)］明显降低（P<0.05）。此外,HIBD模型组缺血侧（左侧）的脑组织含水量高于非缺血侧（右侧）（P<0.05）,EP治疗后两侧的脑组织含水量无显著差异（P>0.05）,提示EP减轻了缺血侧的脑水肿。同时HIBD+EP组缺血侧脑皮质和海马每个视野的凋亡细胞数目分别为96.63±10.08和41.91±9.96,较模型组（111.54±1.64和51.73±1.77）明显减少,但仍多于假手术组（P<0.05）。HIBD+EP组左脑萎缩程度为(13.25±5.19)%,较HIBD模型组［(20.32±5.10)%］明显减轻（P<0.05）。结论：EP具有抗氧化功能,能减轻脑水肿,减少脑细胞凋亡,减轻脑萎缩,对HIBD新生大鼠脑组织具有保护作用。     

山楂对冠心病同型半胱氨酸血症的影响

目的：观察口服山楂对冠心病同型半胱氨酸血症及高脂血症的影响。方法：随机选择53例经荧光探测仪测定空腹血确诊为高同型半胱氨酸血症及高脂血症的冠心病患者，均在常规治疗基础上给予山楂（河北产）每日30 g，分三次口服，治疗期间规律饮食、戒烟。治疗后第4周、8周、12周，各取清晨空腹静脉血3 mL（0.1% EDTA抗凝），测定用药后各阶段血浆HCY水平及第12周血浆TC、TG的浓度。结果：治疗前空腹血HCY浓度为(43.36±8.81) μmol/L，血浆TC浓度为(6.26±0.62) mmol/L，TG为(2.45±0.73) mmol/L。口服山楂后血浆HCY浓度第4周为(35.14±8.34) μmol/L（P<0.01），第8周为(21.96±5.76) μmol/L（P<0.01），第12周为(13.21±3.39) μmol/L（P<0.01）；第12周血浆TC的浓度为(5.28±0.57) mmol/L（P<0.01），TG为(16.8±0.60) mmol/L（P<0.01）。结论：山楂可显著降低冠心病患者血浆HCY和TC、TG的浓度。     

猪血管内皮细胞上人天然抗体识别的抗原表位的研究

为了测定猪血管内皮细胞膜表面可能存在的碳水化合物抗原表位,5个人工合成的糖结合物(还原胺化法)和猪胃粘膜糖肽片断被用于中和人天然抗体.然后再用这类中和之后的人血清与猪血管内皮细胞行补体依赖的细胞毒反应(MTT法),并与牛血清白蛋白对比.有2个糖结合物能部分和人天然素体,它们是:(1)去唾液酸分枝双糖-牛血清白蛋白;(2)Le~a-Le~x钥孔虫戚血蓝素.这些糖结合物均含有Gal(β1,3)GlcNAc或Gal(β1,4)GlcNAc.猪胃粘膜糖肽片断具有较强地抑制人血清细胞毒性的作用,除含有Gal(β1,3)GlcNAc、Gal(β1,4)GlcNAc之外,它的主要结构为GlcNAc(χ1,4)Gal.用钥孔虫戚血蓝素作载体能加强糖结合物中和人天然抗体的作用.提示天然抗体认别成簇状的糖表位结构.     

外周血维生素D3在原发性干燥综合征患者中的表达及与病情程度的关系

目的：探讨25（OH）D3在原发性干燥综合征患者中的表达及与病情程度的关系。方法：收集2015年3月至2016年3月于我院就诊的98例原发性干燥综合征患者。按照SSDAI积分分为pSS稳定期组（n=49例）和pSS活动期组（n=49例）,同期选择98例在我院体检的健康志愿者作为对照组。采集所有实验者的B淋巴细胞指标（CD27^high浆细胞、CD27⁺记忆性B细胞）和T淋巴细胞指标肿瘤坏死因子（TNF-α）、IL-6、IL-10、IL-17,检测并分析。采用ELISA法检测维生素D3的水平。观察pSS组和对照组B淋巴细胞指标、T淋巴细胞指标对比,pSS活动期组和pSS稳定期组B淋巴细胞指标、T淋巴细胞指标对比。结果：在B淋巴细胞中,pSS组CD27^high浆细胞、CD27+记忆性B细胞显著低于对照组［（0.87±0.23）vs（1.80±0.20）,（21.75±4.32）vs（33.92±3.19）］（P＜0.05）,在T淋巴细胞指标中,pSS组TNF-α、IL-6、IL-17水平显著高于对照组［（135.89±15.83）μg/L vs（69.03±11.07）μg/L,（98.52±20.17）μg/L vs（40.02±9.42）μg/L,（89.36±16.26）μg/L vs（45.92±9.01）μg/L］（P＜0.05）,IL-10水平显著低于对照组［（46.16±17.05）μg/L vs（9689±10.37）μg/L］（P＜0.05）;在B淋巴细胞中,pSS活动期组CD27high浆细胞、CD27+记忆性B细胞显著低于pSS稳定期组［（0.70±0.10）vs（1.23±0.30）,（17.04±1.90）vs（25.10±2.80）］（P＜0.05）,在T淋巴细胞指标中,pSS活动期组TNF-α、IL-6、IL-17水平显著高于pSS稳定期组［（205.86±28.98）μg/L vs（124.57±16.04）,（114.02±20.73）μg/L vs（81.98±7.40）μg/L,（101.86±15.97）μg/L vs（76.39±4.53）］μg/L（P＜0.05）,IL-10水平显著低于pSS稳定期组［（31.92±8.09）μg/L vs（60.86±6.18）μg/L］（P＜0.05）,pSS活动组为(22.45±3.27)pg/ml,pSS稳定组为(39.03±3.21)pg/ml,对照组为(41.64±5.59）pg/ml。活动组25(OH)D3 水平低于稳定组和对照组(P＜0.05),但稳定组与对照组比较差异无统计学意义(P＞0.05)。结论：原发性干燥综合征患者25（OH）D3水平显著低于正常人,25(OH)D3的不足可使T淋巴细胞和B淋巴细胞浸润及活化,造成腺体功能损伤,与原发性干燥综合征的病情程度以及免疫功能之间存在密切的关系。     

硝基酪氨酸和诱导型一氧化氮合酶在大鼠胎粪吸入性肺损伤中表达的研究

目的：观察大鼠胎粪诱导肺损伤时肺组织硝基化酪氨酸和诱导型一氧化氮合酶（iNOS）表达的改变，探讨两者在此种损伤中的作用。 方法： 16只雄性SD大鼠，随机分为对照组和胎粪组，分别由气管插管注入生理盐水或20%胎粪生理盐水混悬液1 mL/kg。24 h后取材，观察支气管肺泡灌洗液（BALF）细胞计数，比色法检测肺组织匀浆髓过氧化物酶（MPO）活性、一氧化氮（NO）含量，Western blot法测定硝基酪氨酸和iNOS蛋白表达改变。 结果： 胎粪组BALF细胞计数、肺组织MPO活性、NO含量分别为(4.04±1.01)×109cells/L、(1.49±0.22)U/g wet lung tissue、(12.77±5.00)mmol/g protein，对照组BALF细胞计数、肺组织MPO活性、NO含量分别为(0.53±0.19)×109cells/L、(0.62±0.16)U/g wet lung tissue、(4.89±1.32)mmol/g protein，两组比较差异显著（均P<0.01）；Western blot结果显示胎粪组肺组织硝基酪氨酸和iNOS蛋白表达明显强于对照组，分别为0.46±0.19和1.49±0.60，与对照组（0.15±0.04和0.09±0.04）比较, 差异显著（均P<0.01）。 结论： 胎粪可诱导iNOS表达增强并产生过量的硝基酪氨酸，两者可能在胎粪性肺损伤发病机制中发挥重要作用。     

急性冠状动脉综合征患者血浆基质金属蛋白酶及其抑制因子的变化

目的：研究急性冠状动脉综合征患者血浆基质金属蛋白酶（MMP-9）及其抑制因子（TIMP-1）的变化。方法：采用夹心酶免疫定量分析技术，测定30例急性冠状动脉综合征患者、29例稳定型心绞痛患者和17例正常对照血浆MMP-9和TIMP-1的变化。结果：3组间年龄、性别、总胆固醇、甘油三脂、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇无显著差异。急性冠脉综合征组高敏C反应蛋白(4.336±1.334) mg/L、MMP-9 (13.145±9.796) μg/L、TIMP-1 (1.363±0.605) μg/L、MMP-9/TIMP-1 (10.013±7.195) 显著高于稳定型心绞痛组[ 分别为(2.205±0.458) mg/L、(2.206±1.996) μg/L、(0.688±0.389) μg/L和(3.249±1.987) ]和正常对照组[ 分别为(1.625±0.434) mg/L、(1.663±1.271) μg/L、(0.583±0.421) μg/L和(5.169±7.416) ]，MMP-9与hs-CRP、TIMP-1、MMP-9/TIMP-1呈正相关。结论：急性冠脉综合征患者存在着由炎症反应导致的以MMP-9升高为主的MMP-9/TIMP-1失衡状态，血浆MMP-9/TIMP-1有可能作为反映急性冠脉综合征患者脆性斑块的指标。     

调节性T细胞促进球囊损伤颈动脉内皮化的作用及机制

目的 探讨调节性T细胞（Treg细胞）促进球囊损伤颈动脉内皮化的作用及机制。 方法 使用Treg细胞分选试剂盒分选大鼠脾脏Treg细胞;构建大鼠颈动脉损伤模型;模型制作成功后分为对照组（尾静脉注射相同体积的生理盐水）、血管内皮生长因子（VEGF）组（尾静脉注射VEGF, 20 μmol/kg）和Treg细胞组（尾静脉注射1×105个Treg细胞）。HE染色检测内皮化情况;ELISA和免疫组织化学法检测血清中白细胞介素（IL）-10、转化生长因子-β（TGF-β）、IL-1β和肿瘤坏死因子α（TNF-α）的含量;流式细胞术检测单核细胞、T细胞和内皮祖细胞（EPC）的比例。 结果 组织学染色结果显示,对照组未见内皮细胞层的形成,Treg细胞组可见较多内皮细胞覆盖在颈动脉内层;免疫组织化学结果显示,对照组与Treg细胞组IL-10、TGF-β、IL-1β和TNF-α蛋白表达差异均有统计学意义（t=8.252,P<0.01;t=3.254,P<0.05;t=6.237,P<0.01;t=7.529,P<0.01）。ELISA结果显示,对照组IL-10、TGF-β、IL-1β和TNF-α的含量分别为（17.38±2.595）μg/L、（4.750±1.549）μg/L、（11.65±1.908）μg/L和（1.163±0.3333）μg/L;Treg细胞组的含量分别为（58.43±6.060）μg/L、（14.17±2.250）μg/L、（1.550±0.3819）μg/L和（0.2100±0.06938）μg/L,差异有显著性（t=6.170,P<0.01;t=3.558,P<0.01;t=5.191,P<0.01;t=2.800,P<0.05）;流式细胞术的结果显示,对照组CD34+VEGFR-2+EPC比例为（0.2838±0.01975）%,Treg细胞组为（0.5667±0.05993）%,差异有显著性（t=4.483,P<0.01）;IL-10阻断组EPC比例为（0.4807±0.03067）%,相对于Treg细胞组,差异不具有统计学意义（t=1.278,P>0.05）;TGF-β阻断组EPC比例为(0.3082±0.02291)%,相对于Treg细胞组,差异有显著性（t=4.029,P<0.01）。 结论 Treg细胞通过诱导EPC动员,促进球囊损伤颈动脉的快速内皮化。     

Glycosylated components of African swine fever virus particles

Extracellular African swine fever (ASF) virus particles were specifically agglutinated by several lectins, suggesting the presence of surface glycosylated component(s) containing at least glucose, mannose, or both; galactose, N-acetylgalactosamine, or both; N-acetylneuraminic acid and N-acetylglucosamine, but not fucose. When virions were purified from infected Vero cells labeled with [14C]glucosamine, [14C]galactose and analyzed by polyacrylamide gel electrophoresis, no major structural glycoproteins were detected. However, several species of glycolipids were found when virions were extracted with organic solvents and analyzed by thin layer chromatography. These, plus two minor glycosylated structural components, of apparent mol wt 230K and 95K, could account for the agglutination of ASF virions with concanavalin A.     

血小板膜外周型苯二氮卓受体在初发脑梗死后抑郁中的作用

 目的：观察卒中后抑郁（PSD）患者血小板膜外周型苯二氮卓受体（PBRs）的变化,探讨PBRs在PSD中的作用。方法：卒中后抑郁组为初发脑梗死后PSD患者43例、脑梗死组为初发脑梗死患者59例、对照组为健康献血者46名。采用Hamilton抑郁量表（HAMD）评定患者抑郁程度。提取外周血血小板膜,应用放射性配基［3H］PK11195结合实验测定PBRs特异结合活性。结果：［3H］PK11195结合活性3组之间有显著差异（P<0.01）。与对照组［（298.2±25.1) pmol/（g protein）］比较,脑梗死组［3H］PK11195结合活性［（1 410.8±41.4） pmol/(g protein)］显著升高（P<0.01）。与脑梗死组比较,PSD组［3H］PK11195结合活性［（361.7±30.6） pmol/g protein］显著降低（P<0.01）。PSD组男性、女性患者之间比较,［3H］PK11195结合活性差异不显著。PSD组［3H］PK11195结合活性与患者病程无显著相关性（r=0.27,P＞0.05）,与HAMD评分呈显著负相关（r=-0.44,P＜0.01）。结论:PSD患者血小板膜PBRs结合活性下降, PBRs影响抑郁程度。     

Serum lipid and lipoprotein levels in Ghanaians with diabetes mellitus and hypertension.

Both diabetes mellitus and hypertension alter lipid and lipoprotein metabolism and increase the risk of coronary artery disease. We have reported previously on lipid and lipoprotein levels in healthy Ghanaians, and this study deals with the levels of these biochemical parameters in Ghanaians with diabetes mellitus and hypertension. Fasting serum lipoproteins were determined on blood samples drawn from healthy male and female Ghanaians as well as age-matched individuals with either diabetes or hypertension. Cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and fasting blood glucose were measured. Low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) were derived. Total serum cholesterol levels were 4.43 +/- 0.22 mmol/L and 4.67 +/- 0.26 mmol/L for diabetic males and females, respectively. High-density lipoprotein was 1.55 +/- 0.09 mmol/L and 1.50 +/- 0.09 mmol/L for male and female diabetics, respectively. Lipid and lipoprotein levels in the hypertensive patients did not differ from the above values. The levels of cholesterol and lipoprotein obtained in Ghanaians with hypertension and diabetes mellitus were similar to those of their age-matched healthy controls. These results suggest a reduced risk of coronary artery disease from the atherogenic effects of cholesterol in Ghanaians with diabetes mellitus and hypertension.     

高果糖饮食对大鼠肾脏的毒性作用

 [摘要] 目的　观察高果糖饮食诱导的高甘油三酯血症对大鼠肾组织病理形态的影响,探讨脂质肾毒性的作用机制。方法 将32只大鼠分为正常对照组(N组,n=16)及高果糖组(F组,n=16),8及16周时分批处死,检测各组大鼠的肾功能、空腹血糖、血脂及24h尿微量白蛋白;检测大鼠肾皮质甘油三酯含量;采用免疫组化分析IV型胶原及α-平滑肌动蛋白表达和定位,并观察肾脏病理变化。电镜观察肾脏基底膜变化。结果　8周和16周时,高果糖组血中甘油三酯分别达(1.65+0.86)mmol/L、（2.13+0.87）mmol/L,极低密度脂蛋白分别达(0.75+0.39)mmol/L、(0.97+0.40)mmol/L,肾组织中甘油三酯分别达(7.21+2.20)mg/g、(7.92+3.05)mg/g,24h尿微量白蛋白分别达(63.00+12.00)μg、(150.00+48.00) μg,较对照组明显升高（P<0.05）;肾脏病理改变加重,基底膜增厚,肾组织IV型胶原α-SMA表达明显增加（P<0.05）。结论　高果糖饮食可诱导大鼠高甘油三酯血症,并使肾组织油三酯水平增加导致肾脏损伤。     

Myocardial metabolism of triacylglycerol-rich lipoproteins in type 2 diabetes

Cardiac utilisation of very-low-density lipoprotein (VLDL) and chylomicrons (CM) was investigated in the ZDF rat model of type 2 diabetes, in order to define the role of triacylglycerol (TAG) metabolism in the development of contractile dysfunction. Hearts from obese diabetic and lean littermate control rats were perfused with VLDL and CM from diabetic and control rats. Metabolic fate of the lipoprotein TAG and contractile function were examined. Myocardial utilisation of both VLDL- and CM-TAG was increased in the diabetic state. Diabetic hearts oxidised diabetic lipoprotein-TAG to a greater extent than control lipoproteins; glucose oxidation was decreased. There was no difference in lipoprotein-TAG assimilation into diabetic heart lipids; diabetic lipoproteins were, however, a poor substrate for control heart tissue lipid accumulation. Although the proportion of exogenous lipid incorporated into tissue TAG was increased in diabetic hearts perfused with control lipoproteins, this effect was not seen in diabetic hearts perfused with diabetic lipoproteins. Myocardial heparin-releasable lipoprotein lipase (LPL) activity was moderately increased in the diabetic state, and diabetic lipoproteins increased tissue-residual LPL activity. Cardiac hydraulic work was decreased only in diabetic hearts perfused with diabetic CM. Compositional analysis of diabetic variant lipoproteins indicated changes in size and apoprotein content. Alterations in cardiac TAG-rich lipoprotein metabolism in type 2 diabetes are due to changes in both the diabetic myocardium and the diabetic lipoprotein particle; decreased contractile function is not related to cardiac lipid accumulation from TAG-rich lipoproteins but may be associated with changes in TAG-fatty acid oxidation.     

孕期尼古丁暴露致成年子代大鼠中枢对血管紧张素II的高反应性

目的 探讨孕期尼古丁暴露后,子代大鼠中枢对血管紧张素II（AngII）的反应性。方法 对孕期尼古丁暴露的子代大鼠（n =7）脑室内注射AngII、洛沙坦(Los)和PD123319（PD）后,观察尼古丁子代（尼古丁组）平均动脉压（MAP）、血气与正常大鼠子代（对照组,n =7）之间的差异,并检测下丘脑前区（AHA）c-Fos表达,AngII受体1a（AT1aR）、AT1bR和AT2R mRNA的变化,以及AHA区AT1R、AT2R蛋白表达水平。结果 尼古丁组基础MAP与对照组无差异,但脑室内注射 AngII后,尼古丁组大鼠MAP高于对照组［（120.36±6.23） mmHg （109.87±6.86）mmHg,P <0.05］,AHA区的c-Fos表达也明显强于对照组（25.8±2.91 比6.42±1.52,P <0.05）,而Los预处理后,两组MAP无明显变化,但PD预处理后,尼古丁组MAP仍高于对照组。并且尼古丁组AHA区的AT1aR mRNA高于对照组（1.23±0.05 比 1.00, P <0.05）,AT1R蛋白表达也高于对照组（0.581±0.06 比 0.353±0.05,P <0.05）。结论 孕期尼古丁暴露可导致子代大鼠AHA区AT1aR mRNA及AT1R蛋白高于对照组,可能导致中枢对AngII的反应性增强。     

The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury.

The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel-exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low-density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions.     

The Asn9 variant of lipoprotein lipase is associated with the — 93G promoter mutation and an increased risk of coronary artery disease

Two mutations in the lipoprotein lipase (LPL) gene, a T to G transition at position −93 of the proximal promoter region and an Asp9Asn substitution in exon 2, were examined in 762 Dutch males with angiographically-diagnosed coronary artery disease (CAD) and 296 healthy normolipidemic Dutch males. The two mutations exhibited strong linkage disequilibrium (D'=0.975). A significantly higher proportion of cases (4.86%) than controls (1.37%) carried the −93G/Asn9 allele (p=0.008). In the combined sample of cases and controls, adjusted mean plasma total cholesterol (TC) levels were significantly higher in −93G/Asn9 carriers (6.20±0.13 mmol/l) than in non-carriers (5.93±0.03 mmol/l; p=0.048), while mean high-density lipoprotein cholesterol (HDL-C) levels were lower in carriers (0.88±0.03 mmol/l) than in non-carriers (0.98±0.01 mmol/l; p=0.002). There was a trend towards higher triglyceride (TG) levels in carriers (1.96±0.14 mmol/l) compared with non-carriers (1.73±0.03 mmol/l) (p=0.08). Additionally, carrier frequencies in tertiles of TC, HDL-C, TG, and LPL activity, suggested an association of the −93G/Asn9 variant with higher TC and TG levels, and with lower HDL-C and LPL activity levels. Logistic regression revealed a significant odds ratio (OR) for the combined −93G/Asn9 genotype in CAD cases relative to controls (OR: 5.36; 95% CI: 1.57–18.24), with age, body mass index (BMI), smoking, and plasma total- and HDL-cholesterol levels included in the model. In conclusion, we show that the LPL Asp9Asn mutation is in non-random association with a T→G substitution at position −93 of the proximal promoter region and that the combined −93G/Asn9 genotype predisposes to decreased HDL-C levels and an increased risk of CAD.