多不饱和脂肪酸不同构成及配比对ApoE－/－小鼠动脉粥样硬化的影响

目的观察多不饱和脂肪酸不同构成及其配比对ApoE~(-/-)小鼠动脉粥样硬化(As)的预防作用,为合理使用脂肪酸预防As提供科学依据。方法设置对照组、模型组、3组实验油组,按饱和脂肪酸(SFA)∶单不饱和脂肪酸(MUFA)∶多不饱和脂肪酸(PUFA)=0.25∶1∶1比例配制3种实验油定制饲料。设计实验油1和油2中ω-6/ω-3 PUFA比例为2.5∶1,实验油3中ω-6/ω-3 PUFA比例为10∶1。其中实验油1中ω-3 PUFA来源为α-亚麻酸(ALA),实验油2及实验油3中ω-3 PUFA来源为二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)和α-亚麻酸(ALA)。记录小鼠体质量变化,主动脉大体油红O染色及主动脉窦HE染色观察主动脉内膜斑块形成情况;肝脏油红O染色观察肝脏脂质蓄积情况;酶法检测肝脏甘油三酯(TG)和总胆固醇(TC)水平;酶法检测血清TG、TC、低密度脂蛋白胆固醇(LDLC)和高密度脂蛋白胆固醇(HDLC)水平。结果与模型组比较,3组实验油均能减少主动脉As斑块形成(P0.05),降低肝脏TG、TC(P0.05),降低血清TG、TC、 LDLC(P0.05),改善肝脏脂质蓄积。与实验油1组及实验油3组比较,实验油2组更能有效抑制主动脉As斑块形成(P0.05),显著降低肝脏TG、TC(P0.05),降低血清TG、TC、LDLC,升高血清HDLC(P0.05),改善肝脏脂质蓄积。结论减少SFA摄入,增加MUFA和PUFA摄入具有抗动脉粥样硬化的作用,EPA、DHA和ALA共同作为ω-3 PUFA的供体比ALA单独提供ω-3 PUFA抗动脉粥样硬化效果更好,低比例ω-6/ω-3PUFA比高比例ω-6/ω-3PUFA抗动脉粥样硬化效果更好。     

诺衡调节血脂水平后

51例原发性高脂血症患者,其血清总胆固醇(TC)≥5.72mmol/L(220mg%)及/或甘油三酯(TG)≥1.65mmol/L(150mg%)。治疗组36例,服诺衡(gemfibrozil)600mg,每天两次,共4周。对照组15例,不用任何血脂调节剂。治疗组服用诺衡4周后,血清TC、TG较服药前明显降低,高密度脂蛋白胆固醇(HDL-C)明显上升,同时伴有血清6-酮-前列腺素F_(1a)(6-Keto-PGF_(1a))及血浆纤维蛋白自然溶解活性(FA)明显上升,而血清血栓素B_2(TXB_2)及血浆纤维蛋白原(Fg)明显下降。对照组各项指标自始至4周末均无明显变化。     

普伐他汀对红细胞膜n-6、n-3脂肪酸成分影响的研究

目的　观察普伐他汀对原发性高脂血症患者红细胞膜 n3、n6脂肪酸成分的影响。方法　 32例原发性高脂血症患者应用普伐他汀 10 m g qd,采用自身对照的方法分别于治疗前、治疗后 6周及 12周时测定患者血浆脂质成分 ,并用气相色谱法测定红细胞膜脂肪酸成分。结果　本组患者经治疗后胆固醇 (TC)、三酰甘油 (TG)、低密度脂蛋白胆固醇 (L DL- C)、载脂蛋白 B10 0 (apo B10 0 )均明显降低 (P<0 .0 5～ 0 .0 0 1) ;高密度脂蛋白胆固醇 (HDL- C)均升高 (P<0 .0 5～ 0 .0 0 1) ,红细胞膜 n- 6脂肪酸 ,以花生四烯酸为代表 (AA )显著降低 (P<0 .0 1) ,n- 3脂肪酸 ,即廿碳五烯酸 (EPA)和廿二碳六烯酸 (DHA )均显著升高 (P<0 .0 1)。 n- 6 / n- 3比值有降低 ,TC、TG、L DL - C下降与红细胞膜 AA / EPA、AA/ DHA比值降低呈显著正相关 (P<0 .0 1)。结论　普伐他汀在有效调节血脂的同时能调节红细胞膜 n3、n6脂肪酸成分     

氟伐他汀治疗冠心病的可能机制探讨

目的 观察氟伐他汀的降脂效果并探讨其治疗冠心病的可能机制。方法 对30例合并高胆固醇血症的冠心病患者给予氟伐他汀40mg/每晚治疗,分别于服药前4周、服药后0、6、12周取血测定一氧化氮(NO)、6-酮-前列腺素Flα(6-K-PGFlα)、C-反应蛋白(CRP)及总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平。结果 服药12周末血TC、LDL-C和HDL-C变化分别为:-20.9%、-25.6%和+8.3%;血中NO和6-K-PGFlα较治疗前明显升高(P<0.05),CRP明显降低(P<0.05)。结论 氟伐他汀在调节血脂的同时,尚有保护血管内皮、抑制炎症反应和减少血小板聚集作用。     

淡水鱼对血清中不饱和脂肪酸含量的调节及其对血脂的影响

目的 :探讨进食淡水鱼对调节人体不饱和脂肪酸含量及其对血脂的影响。方法 :渔民组 79例 ,非渔民组 77例。采早晨空腹静脉血液 ,检测血清中ω 3(EPA、DHA)等不饱和脂肪酸含量和总胆固醇、甘油三酯、高密度脂蛋白 ,低密度脂蛋白 ,载脂蛋白B、AI及其比值等血脂含量 ,将各项指标进行t检验统计学分析。结果 :渔民组不饱和脂肪酸含量均较非渔民组明显增高 (P <0 .0 1) ;不饱和脂肪酸含量增高者其血清脂质水平明显降低(P <0 .0 5～ <0 .0 1)。结论 :长期进食淡水鱼能提高人体血中不饱和脂肪酸水平及降低血清脂质水平     

普伐他汀、非诺贝特、鱼油对血脂及血浆内皮素、血栓烷B2水平的影响

目的　观察原发性高脂血症患者分别应用三种不同血脂调节剂后对血脂及血浆内皮素(endothelin,ET 1)、血栓烷B2 (thromboxaneB2 ,TXB2 )水平的影响。方法　 91例原发性高脂血症患者 ,其中 ,男 67例 ,女 2 4例 ,平均年龄 (5 3 1± 8 9)岁。随机分别服用普伐他汀(pravastatinP,n=3 0例 )、非诺贝特(fenofibrateF。n=3 3例 )、鱼油 (fishoilFO。n=2 8例 )血脂调节剂 12周后 ,比较其服药前后调脂剂的疗效及对ET 1,TXB2 ,6 酮 前列环素 (6 酮 PGF1a)水平的影响 ,并分析血脂与ET 1、TXB2 / 6 酮 PGF1a比值间的相互关系。高脂血症类型 :Ⅱa 型 19例 ,Ⅳ型 5 2例 ,Ⅱb 型 2 0例。结果　治疗 12周后 ,三组血清甘油三酯 (TG)、低密度脂蛋白 (LDL C)、载脂蛋白B10 0 (apoB10 0 )水平均明显降低 (P <0 0 5～0 0 0 1)。P组与F组血清胆固醇 (TC)水平降低显著性 (P <0 0 5～ 0 0 0 1)。血清高密度脂蛋白 (HDL C)水平三组均有升高 ,但仅F组有显著性 (P <0 0 5～ 0 0 0 1)。HDL C与TG水平三组均呈负相关 (P<0 0 5～0 0 0 1)。血浆ET 1水平三组均有显著降低 (P <0 0 0 1) ,TXB2 / 6 酮 PGF1a比值三组治疗前高于健康人 ,治疗后均降低 (P <0 0 1～ 0 0 0 1)。血浆ET 1水平及TXB2 / 6 酮 PGF1a比值下降 (除FO组TC)     

益气活血解毒汤对实验性动脉粥样硬化家兔血脂、前列环素及血栓素A2的影响

目的通过高脂饲料喂饲诱发动脉粥样硬化家兔模型,探讨中药复方益气活血解毒汤对家兔动脉粥样硬化的干预作用及其作用机制。方法24只日本雄性大耳白兔随机分为4组,分别为空白对照组、模型对照组、益气活血解毒汤组及辛伐他汀组。10周后测定各组血清总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、血栓素B2（TXB2）、6-酮-前列腺素（6-keto-PGF1α）的含量。结果模型对照组TC,TG,LDL-C,TXB2较空白对照组有不同程度升高（P〈0.05或P〈0.01）,6-keto-PGF1α及HDL-C显著下降（P〈0.05）。益气活血解毒汤组及辛伐他汀组TC,TG,LDL-C及TXB2均低于模型对照组,6-keto-PGF1α及HDL-C升高明显（P〈0.01）,益气活血解毒汤组HDL-C与辛伐他汀组比较有所升高（P〈0.05）。结论益气活血解毒汤对家兔动脉粥样硬化有明显的预防和治疗作用,调节血脂、维持PGI2/TXA2的平衡可能是其作用机制之一。     

高脂血症患者血脂蛋白a水平的研究

目的　研究高脂血症 (HLP)患者血脂蛋白a[Lp(a) ]水平的变化。方法　用免疫比浊法测定 30例HLP患者血Lp(a) ,同时测定研究对象血胆固醇 (TC)、甘油三酯(TG)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇(LDL C)、载脂蛋白AI(ApoA1)及载脂蛋白B(ApoB)。结果　HLP患者血Lp(a)显著高于对照组 (2 17 5± 14 5 3vs15 0 3± 14 9 8,P <0 0 5 )。HLP患者血Lp(a)与TC的相关系数为 0 6 4 3(P <0 0 1)。结论　HLP患者血Lp(a)明显升高 ,是冠心病 (CHD)、动脉粥样硬化 (AS)的危险因子。     

原发性高血压患者合并血脂异常与血浆胰岛素浓度的关系

目的　探讨原发性高血压患者血浆胰岛素浓度与血脂、脂蛋白及载脂蛋白水平的关系。方法　比较高血压组与对照组及高血压患者按胰岛素水平分组后与对照组的总胆固醇 (TC)、三酰甘油 (TG)、高密度脂蛋白胆固醇(HDL- C)、低密度脂蛋白胆固醇 (L DL- C)、载脂蛋白 AI(apo AI)、载脂蛋白 B(apo B)和血浆胰岛素的水平。结果　原发性高血压患者血脂成分及胰岛素水平均较对照组有明显差异 (分别 P<0 .0 1和 P<0 .0 5 )。按胰岛素水平分组 ,A组胰岛素浓度 <15 ml U / L ,B组胰岛素浓度≥ 15 m IU / L而 <2 5 ml U / L和 C组胰岛素浓度≥ 2 5 m l U /L ;各组与对照组比 ,高血压患者 TC、TG、L DL - C、apo B明显升高 (分别 P<0 .0 1和 P<0 .0 5 ) ,HDL - C、apo AI显著降低 (P<0 .0 1)。高血压患者 TG浓度随胰岛素水平增高而明显增加。结论　原发性高血压患者血浆胰岛素水平增加是其脂代谢异常的原因之一 ,而血脂异常的分布与 TG浓度升高有关     

雌-孕激素替代治疗对绝经后妇女血脂和脂蛋白代谢的长期作用

目的　观察雌 孕激素替代治疗 (HRT)对绝经后妇女血脂和脂蛋白代谢的长期作用。方法　 193例健康绝经后妇女分为A组 (高胆固醇血症组 ) 6 3例、B组 (无高胆固醇血症组 ) 6 0例和C组 (对照组 ) 70例 ,A、B组均给予倍美力 (天然结合型雌激素 ) 0 .6 2 5mg d +安宫黄体酮 2mg d治疗 ,连续 3年监测血清性激素、血脂及脂蛋白水平。结果A组总胆固醇 (TC) ,低密度脂蛋白胆固醇 (LDL C)水平分别下降 12 .1% (P <0 .0 1)、15 .7% (P <0 .0 1) ,B组LDL C下降 4 .5 % (P <0 .0 5 ) ,A、B组高密度脂蛋白胆固醇 (HDL C)水平均明显升高 ,分别为 15 .1% (P <0 .0 1)、2 5 .8% (P <0 .0 1) ,均在第 3个月就出现明显改变 ,并在服药期间可保持疗效 ,对照组则变化不明显。B组TC有下降趋势 ,各组甘油三酯 (TG)均有增高趋势 ,但差异均无显著性意义。A、B组血清 17 β雌二醇 (17 βE2 )和孕酮于第 3个月显著升高 ,血清卵泡刺激素、黄体生成素水平则于第 6个月明显下降 ,并在服药期间可保持疗效 ,而对照组变化不明显。结论　绝经后妇女HRT能改善血清TC、TG、LDL水平 ,并在服药期间可保持疗效 ,对具有高胆固醇血症者效果更佳     

Epidemiology of primary biliary cholangitis in Italy: Evidence from a real-world database

BackgroundPrimary biliary cholangitis is an autoimmune disease affecting the interlobular bile ducts. Limited information is available on its epidemiology and treatment in Italy.AimsTo describe primary biliary cholangitis epidemiology and investigate treatment patterns for Italian patients with this disease.MethodsElectronic medical records from 900 general practitioners (part of the QuintilesIMS™ Longitudinal Patient Databases) were examined. Demographics were compared with those from the Italian National Institute of Statistics dataset. The International Classification of Diseases, Ninth Revision, biliary cirrhosis code 571.6 was used for diagnosis, and data on comorbidities, concomitant medications, medical examinations, specialist referrals, and treatments were collected.ResultsThis dataset was representative of the Italian population. Point prevalence of primary biliary cholangitis was calculated as 27.90 per 100,000 and incidence as 5.31 per 100,000 inhabitants/year. Some associations between the disease and comorbidities were sex specific. The most common laboratory assays requested were for liver enzymes, and the majority of patients were not referred to a specialist. Ursodeoxycholic acid was the most common therapy.ConclusionThis can be used as a benchmark for monitoring and identifying unmet needs to improve treatment in Italy.     

Plasma-free eicosapentaenoic acid/arachidonic acid ratio: a possible new coronary risk factor

Seventy-six effort angina patients who had typical angina on exertion documented by treadmill stress test with evidence of ischemic ST-segment depression and 78 healthy volunteers in urban Japan were investigated in this study. Plasma free fatty acids (FFA) in both groups were determined using high-performance liquid chromatography. The relationships between the total cholesterol, high-density lipoprotein (HDL), triglycerides in plasma, and the genesis of coronary heart disease were also examined. The ratio (0.08 +/- 0.08) of eicosapentaenoic acid (EPA)/arachidonic acid (AA) in plasma FFA was significantly lower in effort angina patients than that (0.15 +/- 0.12) in healthy volunteers. The lower ratio was due to significantly lower levels of EPA in the patients than in normals. In 42% of angina patients, the ratio is below 0.03. In all age subgroups except the age 30-39 subgroup, the ratio of EPA/AA was significantly lower in patients than in normals, when divided into four subgroups by using a 10-year age interval. Though the total cholesterol and triglycerides were not significantly different between the two groups, HDL was significantly lower and total cholesterol/HDL ratio was significantly higher in effort angina patients than in healthy volunteers. However, there was no correlation between EPA/AA ratio and HDL in individuals in either group. From these results, it could be concluded that lower EPA/AA ratio is a new coronary risk indicator other than HDL.     

Pharmacologic Properties of the Swelling-Induced Chloride Current of Dog Atrial Myocytes

Pharmacology of Swelling-Induced Chloride Current. Introduction: Swelling-induced chloride currents may contribute to cardiac electrical activity and cell volume regulation. Identification of selective Mockers would aid in understanding the functional contribution(s) of this current.
Methods and Results: Dog atrial cells were used to investigate the pharmacologic properties of the swelling-induced chloride current. Whole cell patch clamp was used. Swelling-induced chloride current was activated by osmotic stress. Initially, the chloride selectivity and calcium independence of the swelling-induced current in dog atrial cells was demonstrated. Subsequently, a number of putative chloride channel blockers were examined. Anthracene-9-earboxylic acid (1mM) and dideoxyforskolin (1000 μ) and extracellular cAMP (5mM) were found to partially inhibit the swelling-induced chloride current (∼50%, 80%, and 10% inhibition, respectively). Niflumic acid (100 μ), nitrophenylpropylamino benzoate (NPPB; 10 to 40 μ), and (+) 2-[(2-cydopentyl-6,7-dichloro-2,3-dihydro-2-melhyl-1-oxy-1H-inden-5-yl)oxy] acetic acid (indanyloxyacetic acid; IAA-94; 100 μ) could fully inhibit the swelling-induced chloride current without decreasing cell size. DIDS (100 μ) and dinitrostilbene disulfonic acid (DNDS;5 mM) fully inhibited outward currents but only partially inhibited inward current.
Conclusions: Niflumic acid, IAA-94, and NPPB were identified as full blockers of cardiac swelling-induced chloride current. Nonspecific effects were identified for each of the full blockers. Experiments that use these agents as functional antagonists should be carefully designed and interpreted with caution.     

肝硬化及非肝消化病患者胆酸,透明质酸及层粘蛋白的变化

目的:研究血清胆酸(CG)、透明质酸(HA)及层粘蛋白(LN)对肝硬化及非肝消化病的诊断意义.方法:用放射免疫法检测血清CG、HA及LN,并计算它们之间的相关系数.结果:肝硬化患者血清CG、HA及LN明显高于健康人及非肝消化病组,差别有高度显著性,HA与LN存在正相关关系.结论:联合检测CC、HA及LN对肝硬化非盯消化病具有重要的意义.     

9-顺维甲酸诱导的肺癌细胞RXRs受体转录水平的变化

目的：检测用9-cis-RA处理前后肺腺癌细胞株PG和A549维甲酸受体RXR。不同时相的表达变化。方法：将两细胞株分别分为9-cis-RA组和对照组，应用细胞计数方法统计每组各时相细胞数，相对定量RT-PCR方法检测组加药前后RXRS各亚型在不同时相的表达变化。结果：加入9-cis-RA后，PG和A549细胞RXRS mRNA转录水平检测结果显示：（1）RXRγ在两细胞株中均有一定水平的基础转录，而RXRα、RXRβ均无基础转录。（2）应用1uM 9-cis-RA后，两细胞株的RXRγ有短暂增高，其余受体转录无明显变化。结论：RXRγ可能参与介导9-cis-RA对两细胞株的诱导分化和凋亡作用。     

非溃疡性消化不良病人胃粘膜分泌维生素C的研究

目的：研究非溃疡性消化不良病人胃粘膜分泌维生素Ｃ（ＶｉｔＣ）的变化以及与幽门螺杆菌（Ｈｐ）感染、胃酸分泌、年龄和性别的关系。方法：用高铁还原法测定血浆和胃液中ＶｉｔＣ浓度，以１小时内ＶｉｔＣ从血液到胃液中的清除率代表胃粘膜分泌Ｖｉｔｃ的能力。结果：胃粘膜的ＶｉｔＣ分泌与Ｈｐ感染与否无关（Ｐ＞０．０５）：ＶｉｔＣ分泌与胃酸分泌呈明显正相关（ｒ＝０．８４），在给五肽胃泌素后，随着胃酸分泌的增加，ＶｉｔＣ分泌也增加：４０岁以上病人的ＶｉｔＣ分泌明显低于３９岁以下病人（Ｐ＜０．０１）。结论：胃粘膜的ＶｉｔＣ分泌不受Ｈｐ感染的影响：ＶｉｔＣ分泌与胃酸分泌明显相关；另外，ＶｉｔＣ分泌也与年龄有关，４０岁以上病人的Ｖｉｔｃ分泌明显减少，推测其胃癌发生率增高可能与ＶｉｔＣ分泌减少有关。     

Birthweights in the Faroe Islands: possible role of isovaleric acid

A high intake of n-3 polyunsaturated fatty acids has been suggested as a factor in prolonged gestation in the population of the Faroe Islands. It is now suggested that isovaleric acid from pilot whales, a species frequently consumed in the Faroe Islands, may be the unusual dietary factor. Fatty acid data for eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) in blood lipids of Faroese and Norwegians is reviewed in terms of the type of fish eaten, apparently mostly lean white fish with DHA much greater than EPA. The popular lean fish, thus, probably provides too little EPA to produce a marked effect on human biochemistry.     

Disturbances in essential fatty acid metabolism in patients receiving long-term home parenteral nutrition

Patients receiving home total parenteral nutrition (HTPN) are at risk for the development of essential fatty acid deficiency (EFAD). This study examined the essential fatty acid status of patients on long-term HTPN for gut failure. Serum phospholipid and triglyceride fatty acids were measured in 11 patients and 10 healthy volunteers. Patients had similar levels of linoleic acid (18:2w6) in serum triglyceride fatty acids but significantly lower levels of 18:2w6 in serum phospholipids compared to controls. Although there was accumulation of Mead acid (20:3w9) in both fatty acid fractions, the ratio of 20:3w9 to arachidonic acid (20:4w6) remained less than 0.2, reflecting an adequate essential fatty acid status in these patients. There were, however, substantial increases in 20:4w6 content in both triglyceride and phospholipid fractions in serum despite the lower levels of 18:2w6 in serum phospholipids, suggesting that an accelerated hepatic conversion of 18:2w6 to 20:4w6 occurs in HTPN patients, as well as the 20-carbon members of w3 (20:3w3) and w9 (20:3w9) families. The determination of optimal parenteral fat intakes should be investigated further as important priority in patients receiving long term HTPN.     

Innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structure

Sialic acids (Sias) are nonulosonic acid (NulO) sugars prominently displayed on vertebrate cells and occasionally mimicked by bacterial pathogens using homologous biosynthetic pathways. It has been suggested that Sias were an animal innovation and later emerged in pathogens by convergent evolution or horizontal gene transfer. To better illuminate the evolutionary processes underlying the phenomenon of Sia molecular mimicry, we performed phylogenomic analyses of biosynthetic pathways for Sias and related higher sugars derived from 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids. Examination of ≈1,000 sequenced microbial genomes indicated that such biosynthetic pathways are far more widely distributed than previously realized. Phylogenetic analysis, validated by targeted biochemistry, was used to predict NulO types (i.e., neuraminic, legionaminic, or pseudaminic acids) expressed by various organisms. This approach uncovered previously unreported occurrences of Sia pathways in pathogenic and symbiotic bacteria and identified at least one instance in which a human archaeal symbiont tentatively reported to express Sias in fact expressed the related pseudaminic acid structure. Evaluation of targeted phylogenies and protein domain organization revealed that the “unique” Sia biosynthetic pathway of animals was instead a much more ancient innovation. Pathway phylogenies suggest that bacterial pathogens may have acquired Sia expression via adaptation of pathways for legionaminic acid biosynthesis, one of at least 3 evolutionary paths for de novo Sia synthesis. Together, these data indicate that some of the long-standing paradigms in Sia biology should be reconsidered in a wider evolutionary context of the extended family of NulO sugars.