缺铁与胆囊结石形成关系的研究

本文检测了 110例 (男 32 ,女 78)胆囊结石病人的血清铁水平 ,低于正常值者 31例 ,占 2 8 2 % ;其中女性 2 5例 ,占80 6 % ,男性仅 6例 ,占 19 4%。铁在肝脏的酶代射过程中扮演着重要角色 ,因此 ,缺铁可能改变胆固醇的代谢 ,增强胆囊结石的形成。     

高密度脂蛋白与冠心病的关系研究进展

流行病学调查、实验研究和临床观察发现,血浆高密度脂蛋白胆固醇作为一个独立的预测因素与冠心病的发病率呈负相关,HDL促进循环中的胆固醇向肝脏转运即“逆向胆固醇转运”,HDL中的两种酶－二乙基对硝基苯磷酸酯酶和血小板激活因子酰水解酶能够降低氧化HDL的形成;通过戒烟、降低到理想体重、规律的需氧锻炼、药物治疗,能绝对或相对的升高HDL－c浓度,降低冠心病的发病率。     

High affinity of sigma1-binding sites for sterol isomerization inhibitors: evidence for a pharmacological relationship with the yeast sterol C8–C7 isomerase

1. The sigma-drug binding site of guinea-pig liver is carried by a protein which shares significant amino acid sequence similarities with the yeast sterol C₈–C₇ isomerase (ERG2 protein). Pharmacologically - but not structurally - the sigma₁-site is also related to the emopamil binding protein, the mammalian sterol C₈–C₇ isomerase. We therefore investigated if sterol C₈–C₇ isomerase inhibitors are high affinity ligands for the (+)-[³H]-pentazocine labelled sigma₁-binding site.
2. Among the compounds which bound with high affinity to native hepatic and cerebral as well as to yeast expressed sigma₁-binding sites were the agricultural fungicide fenpropimorph (K_i 0.005 nM), the antihypocholesterinaemic drugs triparanol (K_i 7.0 nM), AY-9944 (K_i 0.46 nM) and MDL28,815 (K_i 0.16 nM), the enantiomers of the ovulation inducer clomiphene (K_i 5.5 and 12 nM, respectively) and the antioestrogene tamoxifen (K_i 26 nM).
3. Except for tamoxifen these affinities are essentially identical with those for the [³H]-ifenprodil labelled sterol C₈–C₇ isomerase of S. cerevisiae. This demonstrates that sigma₁-binding protein and yeast isomerase are not only structurally but also pharmacologically related. Because of its affiliations with yeast and mammalian sterol isomerases we propose that the sigma₁-binding site is localized on a sterol isomerase related protein, involved in postsqualene sterol biosynthesis.

     

Low serum cholesterol increases the risk of noncardiovascular events: An antagonist viewpoint

Summary Considerable debate concerning the apparent association of low serum cholesterol levels with enhanced noncardiovascular disease mortality has been aired in both scientific and lay publications within the past year. This debate has resulted in some medical experts calling for a moratorium on efforts to reduce serum cholesterol, particularly with drugs, and for a more conservative approach to screening and modifying cholesterol levels for the primary prevention of coronary heart disease (CHD). Observational studies, including the Framingham Heart Study, the Multiple Risk Factor Intervention Trial, the Whitehall Study, and the International Collaborative Group, have not substantiated a cause and effect relationship between naturally occurring low serum cholesterol and noncardiovascular disease mortality, such as cancer. Intervention trials designed to lower high serum cholesterol levels by diet and drugs have also not been conclusively shown to produce excess harm that offsets the benefit of reduced CHD events. Several primary and secondary CHD prevention trials, with sufficient numbers of subjects to provide the statistical power to detect potential detrimental effects of lowering cholesterol levels, are currently in progress and will be very helpful in resolving the concern about noncardiovascular disease mortality.     

噪声对心脏的影响与丹参的拮抗作用及机制的探讨

为探索噪声对心脏的影响及其影响机制, 预防噪声的损伤, 选择雄性Wistar大鼠33 只, 采用配伍组设计分为噪声暴露组 (简称A 组)、噪声暴露 丹参灌胃组 (简称B组) 和正常对照组 (C组)。A 组每天暴露于 (105±1.5) dB(A)、频率250～8000Hz的噪声中4小时; B组每天口服浓度为1g/m l的丹参水溶液1.5m l, 然后与A组同时暴露于相同的噪声中; 正常对照组不给任何处理。实验两月后发现: 暴露组大鼠心肌结构发生改变; 血清组总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL—C) 显著降低; 高密度脂蛋白胆固醇亚组分 (HDL2—C)、HDL3—C)、低密度脂蛋白胆固醇 (LDL—C)、甘油三酯(TG)、极低密度脂蛋白胆固醇(VLDL—C) 值无显著变化; 心肌过氧化脂质(LPO) 含量显著升高, 谷胱甘肽过氧化物酶(GSH—Px) 活力有升高的趋势。提示, 噪声可损伤心肌的结构, 其可能的机制在于降低了HDL—C、HDL2—C的水平、氧化作用增强。丹参组LDL—C显著降低, 心肌组织LPO水平无显著性变化, GSH—Px 活力向正常水平恢复。说明丹参有拮抗噪声的作用, 其作用的可能机制在于丹参的抗氧化作用。然而, 这些研究结果却有待进一步证实     

吸烟与动脉硬化性脑梗塞关系的研究

目的：探讨吸烟与动脉硬化性脑硬塞（ＡＳＣＩ）的关系。方法：对１０２例ＡＳＣＩ患者及１０８例正常人血清载脂蛋白（Ａｐｏ－Ｂ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、总胆固醇（ＴＣ）进行测定及对比分析。结果：ＡＳＣＩ组Ａｐｏ－Ｂ比对照组显著升高（Ｐ＜０．０１）,ＨＤＬ－Ｃ比对照组显著降低（Ｐ＜０．０１）,而ＴＣ两组间无明显差异（Ｐ＞０．０５）。在对照组及ＡＳ－ＣＩ组吸烟者Ａｐｏ－Ｂ均高于非吸烟者（Ｐ＜０．０１,Ｐ＜０．０５）,而ＨＤＬ－Ｃ吸烟者明显低于非吸烟者（Ｐ＜０．０１）。结论：吸烟能促使血清Ａｐｏ－Ｂ增高及ＨＤＬ－Ｃ下降,可以认为吸烟是ＡＳＣＩ的危险因素之一。     

Serum lipoprotein (a) levels in chronic renal failure and liver cirrhosis patients. Relationship with atherosclerosis

This study was carried out to investigate the relationship between lipoprotein (a) levels and the development of atherosclerosis in chronic renal failure (CRF) patients with the possible role of the liver. Serum Lp (a) levels were measured in samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (transaminases (ALT and AST), alkaline phosphatase (ALP) and total bilirubin) investigations and serum cholesterol were carried out for all the subjects enrolled in this study. Serum Lp (a) concentration in CRF patients without LC was 87.25 +/- 6.17 mg/dl, which was significantly higher than all the investigated groups (P < 0.001). Lp (a) concentration in patients with both CRF and LC was 24.65 +/- 1.98 mg/dl, which was not significantly different from the controls, but was significantly higher than that in the subjects with LC only (P < 0.001) where the latter group had significantly low Lp (a) values (11.1 +/- 0.99) relative to all the other groups (P < 0.001). Lp (a) correlated positively with cholesterol in all groups except the LC subjects, but did not correlate with age, or renal function in both CRF groups.     

血浆纤维蛋白原与冠心病患者胆固醇、血液流变学的相关性及药物干预的研究

目的：研究血浆纤维蛋白原（ｆｉｂｒｉｎｏｇｅｎ,ＦＧ）与冠心病（ＣＨＤ）患者胆固醇、血液流变学的相关性及腹蛇抗栓酶（ＡＨＶＡＴ）的治疗效果。方法：观察６６ 例ＣＨＤ 患者血浆ＦＧ、胆固醇（ＣＨＯ）及血浆粘度、低切变血粘度、红细胞聚集指数等血液流变学指标与６０ 例正常人对照。将６６例ＣＨＤ患者随机分为ＡＨＶＡＴ治疗组３２ 例及肝素治疗组３４ 例,观察治疗前后上述指标的变化。结果：ＣＨＤ组血浆ＦＧ、ＣＨＯ、血浆粘度、低切变血粘度、红细胞聚集指数均明显高于正常对照组（Ｐ＜ ０．０１）。ＣＨＤ组患者血浆ＦＧ 水平与ＣＨＯ、血浆粘度、低切变血粘度、红细胞聚集指数呈直线相关（Ｐ＜ ０．０５, Ｐ＜ ０．０１）。用ＡＨＶＡＴ治疗后上述指标明显下降（Ｐ＜ ０．０５）。结论：血浆ＦＧ 升高与ＣＨＯ 升高有关,血浆ＦＧ 升高可导致ＣＨＤ患者血浆粘度、低切变血粘度及红细胞聚集指数的升高,用ＡＨＶＡＴ 治疗可降低ＣＨＤ患者血浆ＦＧ及ＣＨＯ水平,从多方面改善血液流变学指标     

长沙地区小儿载脂蛋白E基因多态性及其对血脂的影响

采用改良的ＰＣＲＲＦＬＰ方法测定长沙地区２９１名儿童载脂蛋白（Ａｐｏ）Ｅ基因型。结果发现ε２,ε３,ε４等位基因的频率分别是００８１,０８５７和００６２。ＡｐｏＥ等位基因频率分布无明显的性别差异（Ｐ＞０．０５）。Ａｐｏε２等位基因携带者与其它ＡｐｏＥ基因携带者相比,血高密度脂蛋白胆固醇、ＡｐｏＥ和ＡｐｏＡ１浓度较高,而总胆固醇、低密度脂蛋白胆固醇、ＡｐｏＢ１００水平较低（Ｐ＜０．０５）。ε４等位基因携带者的血脂、脂蛋白、Ａｐｏ改变则相反（Ｐ＜０．０５）。结果还显示ＡｐｏＥ等位基因对血甘油三酯、脂蛋白（ａ）浓度的影响不明显（Ｐ＞０．０５）。ε２,ε３,ε４等位基因与血总胆固醇、低密度脂蛋白胆固醇、ＡｐｏＢ１００浓度呈等级正相关,与高密度脂蛋白胆固醇、ＡｐｏＡ１及ＡｐｏＥ水平呈等级负相关（Ｐ＜０．０５）。ＡｐｏＥ基因对血清脂类的影响存在性别差异。ＡｐｏＥ基因多态性影响小儿血清脂类代谢。     

Effect of metabolic acidosis on hyperlipidemia in uremia

Nine patients (aged 18±1 years) on maintenance hemodialysis with metabolic acidosis and hyperlipidemia were studied before and after 2 weeks of oral sodium bicarbonate (NaHCO₃) treatment to correct the acidosis. To control for the effect of additional sodium, they were also studied after 2 weeks of an equivalent amount of oral sodium chloride (NaCl). Oral NaHCO₃ treatment led to significant increases in venous pH, serum bicarbonate, and serum 1,25-dihydroxyvitamin D₃ concentrations, but no significant change in total and ionized calcium, phosphate, sodium, potassium, creatinine, blood urea nitrogen, and intact parathyroid hormone concentrations. Oral NaCl did not change any of the biochemical parameters. Before treatment of acidosis, these uremic patients had high serum triglycerides, low serum high-density lipoprotein (HDL) cholesterol, but normal total cholesterol compared with controls. Following 2 weeks of NaHCO₃ treatment, there was a significant decrease in the serum concentrations of triglycerides (P<0.01). HDL and total cholesterol did not change. There were no changes in triglycerides, HDL or total cholesterol from baseline values following 2 weeks of NaCl. Thus treatment of metabolic acidosis ameliorated hypertriglyceridemia but had no effect on HDL and total cholesterol in patients with uremia on hemodialysis. The underlying mechanism may involve 1,25-dihydroxyvitamin D3. Received: 3 August 1998 / Revised: 30 November 1998 / Accepted: 2 December 1998